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Anand E, Joshi S, Reza L, Sahnan K, Lung P, Hart A, Tozer P. A systematic review of outcome measurement instruments used in pouch anal and vaginal fistulae: a COSMIN-based analysis. Qual Life Res 2025; 34:1521-1539. [PMID: 40024986 PMCID: PMC12119747 DOI: 10.1007/s11136-025-03911-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/25/2025] [Indexed: 03/04/2025]
Abstract
PURPOSE Pouch-related fistulae are devastating complications of ileoanal pouch surgery, which is performed to improve the quality of life (QoL) for patients who have had a proctocolectomy. Their management is limited by inconsistent evidence, including using poorly and heterogeneously defined outcomes. This study aims to identify all Outcome Measurement Instruments (OMIs) used in pouch fistula research, including Patient-Reported Outcome Measures (PROMs) and Clinician-Reported Outcome Measures (ClinROMs) and evaluate their quality using COSMIN guidelines to help select the best tool for a standardised core outcome measurement set in a future consensus study. METHODS A systematic review was conducted to identify all OMIs used in ileo-anal pouch fistulae studies, from MEDLINE, Embase, and the Cochrane Library. We evaluated existing OMIs based on COSMIN guidelines and used the GRADE approach to assess evidence quality. Results were synthesized narratively. RESULTS Among 91 studies, 13 OMIs were reviewed. Pouch-specific instruments performed poorly in key domains of reliability, validity, and responsiveness. Only 17.6% of studies assessed QoL using PROMs. The best-performing instruments were the SF-36 and IBDQ. The Ileoanal Pouch Syndrome Severity Score was the only pouch-specific instrument that involved patients in its development and although useful for pouch dysfunction, it lacks specific QoL assessment and was not validated in pouch-fistulae patients. CONCLUSION Existing OMIs for pouch-related fistulae lack adequate measurement properties, with no PROMs specifically validated for QoL in this population and very few instruments involving patients in their development. There is an unmet need for a validated PROM specifically for QoL in pouch-related fistulae.
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Affiliation(s)
- Easan Anand
- St Mark's the National Bowel Hospital, Acton Lane, London, UK.
- Imperial College London, Exhibition Road, London, UK.
| | - Shivani Joshi
- St Mark's the National Bowel Hospital, Acton Lane, London, UK
- Imperial College London, Exhibition Road, London, UK
| | - Lillian Reza
- St Mark's the National Bowel Hospital, Acton Lane, London, UK
- Imperial College London, Exhibition Road, London, UK
| | - Kapil Sahnan
- St Mark's the National Bowel Hospital, Acton Lane, London, UK
- Imperial College London, Exhibition Road, London, UK
| | - Phillip Lung
- St Mark's the National Bowel Hospital, Acton Lane, London, UK
- Imperial College London, Exhibition Road, London, UK
| | - Ailsa Hart
- St Mark's the National Bowel Hospital, Acton Lane, London, UK
- Imperial College London, Exhibition Road, London, UK
| | - Phil Tozer
- St Mark's the National Bowel Hospital, Acton Lane, London, UK
- Imperial College London, Exhibition Road, London, UK
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Lok UW, Tang S, Gong P, Smyrk T, Huang C, DeRuiter RM, Knoll KM, Robinson KA, Sheedy SP, Holmes PM, Zhang J, El Sadaney AO, Harmsen W, Fletcher JG, Knudsen JM, Chen S, Bruining DH. Quantitative assessment of ultrasound microvessel imaging in Crohn's disease: correlation with pathological inflammation. Eur Radiol 2025; 35:2806-2817. [PMID: 39547980 PMCID: PMC12021578 DOI: 10.1007/s00330-024-11156-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 09/18/2024] [Accepted: 09/22/2024] [Indexed: 11/17/2024]
Abstract
OBJECTIVE Ultrasound microvessel imaging (UMI) may offer noninvasive, highly sensitive microvessel imaging for assessing Crohn's disease (CD). However, a quantification metric that demonstrates a strong correlation with pathological inflammation is preferred. The objective was to determine if UMI can enhance IBD imaging interrogations. METHODS UMI was performed on bowel wall segments from patients with CD requiring surgery (n = 55 patients). The vessel-length ratio (VLR) measured by UMI was compared with that obtained using color flow imaging (CFI) and with a histopathologic standard evaluated on all bowel layers. Correlations between VLR and pathological inflammation and receiver operating characteristic (ROC) curves between different groups were analyzed to demonstrate the advantages of VLR with UMI. RESULTS The correlation between VLR from UMI and pathological inflammation (R = 0.80) outperformed that of VLR from CFI (R = 0.59). UMI showed a significant difference (p < 0.01) between mild and non-mild inflammation cases, while CFI could not (p = 0.014). In the ROC analysis, VLR with UMI demonstrated an area under the curve (AUC) of 0.93, compared to the AUC of 0.80 for VLR with CFI, indicating better identification of pathological inflammation between mild and non-mild cases. For a sub-cohort of patients with stricture without penetrating complications (n = 19), VLR using UMI also showed better correlation (R = 0.93) with pathological inflammation scores and a higher AUC (0.96) than those of VLR using CFI (R = 0.66 and 0.88, respectively). CONCLUSIONS UMI enhances vessel detection sensitivity compared to CFI and more accurately reflects transmural inflammation in small bowel Crohn's disease. VLR using UMI strongly correlates with pathological inflammation, distinguishing between mild and non-mild cases, notably including patients with stricture without penetrating complications. KEY POINTS Question Bowel wall thickness and Limberg score from ultrasound are insufficient quantitative metrics for reliable diagnosis of inflammation severity for Crohn's disease. Findings Ultrasound microvessel imaging (UMI) with vessel-length ratio (VLR) is strongly correlated with pathological inflammation and had improved distinction between mild and non-mild inflammation cases. Clinical relevance UMI with VLR has the potential to enhance clinicians' ability to assess disease activity and evaluate therapeutic responses, thereby improving Crohn's disease patient outcomes.
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Affiliation(s)
- U-Wai Lok
- Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA
| | - Shanshan Tang
- Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA
| | - Ping Gong
- Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA
| | - Thomas Smyrk
- Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Chengwu Huang
- Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA
| | - Ryan M DeRuiter
- Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA
| | - Kate M Knoll
- Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA
| | | | | | - Philip M Holmes
- Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA
| | - Jingke Zhang
- Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA
| | | | - William Harmsen
- Research Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, Minnesota, USA
| | - Joel G Fletcher
- Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA
| | - John M Knudsen
- Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA
| | - Shigao Chen
- Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA
| | - David H Bruining
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
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Tiles-Sar N, Neuser J, de Sordi D, Baltes A, Preiss JC, Moser G, Timmer A. Psychological interventions for treatment of inflammatory bowel disease. Cochrane Database Syst Rev 2025; 4:CD006913. [PMID: 40243391 PMCID: PMC12005078 DOI: 10.1002/14651858.cd006913.pub3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/18/2025]
Abstract
BACKGROUND Persons with inflammatory bowel disease (IBD) have an increased risk of suffering from psychological problems. The association is assumed to be bi-directional. Psychological treatment is expected to improve quality of life (QoL), psychological issues and, possibly, disease activity. Many trials have tested various psychotherapy approaches, often in combination with educational modules or relaxation techniques, with inconsistent results. OBJECTIVES To assess the effects of psychological interventions on quality of life, emotional state and disease activity in persons of any age with IBD. SEARCH METHODS We searched Web of Science Core Collection, KCI-Korean Journal Database, Russian Science Citation Index, MEDLINE, Psyndex, PsycINFO, Embase, Cochrane Central Register of Controlled Trials, and LILACS from inception to May 2023. We also searched trial registries and major gastroenterological and selected other IBD-related conferences from 2019 until 2023. SELECTION CRITERIA Randomized controlled trials of psychological interventions in children or adults with IBD compared to no therapy, sham (i.e. simulated intervention), or other active treatment, with a minimum follow-up time of two months, were eligible for inclusion, irrespective of publication status and language of publication. Interventions included psychotherapy and other non-pharmacological interventions addressing cognitive or emotional processing, patient education, or relaxation techniques to improve individual health status. DATA COLLECTION AND ANALYSIS Two raters independently extracted data and assessed the study quality using the Risk of Bias 2 Tool. Pooled standardized mean differences (SMD) for continuous outcomes and relative risks (RR) for event data were calculated with 95% confidence intervals (CI), based on separate random-effects models by age group, type of therapy and type of control. An SMD of 0.2 was considered a minimally relevant difference. SMD ≥ 0.4 was considered a moderate effect. Group analyses were planned to examine differential effects by type of IBD, disease activity, psychological comorbidity, therapy subtype, and treatment intensity. Statistical heterogeneity was determined by calculating the I2 statistic. Publication bias was assessed by presenting a funnel plot and calculating the Eggers Test. GRADE Profiling was used to describe the certainty of the evidence for relevant results. MAIN RESULTS Sixty-eight studies were eligible. Of these, 48 had results reported in sufficient detail for inclusion in the meta-analyses (6111 adults, 294 children and adolescents). Two trials were excluded from the meta-analysis following sensitivity analysis and tests for asymmetry because of implausible results. Most studies used multimodular approaches. The risk of bias was moderate for most outcomes, and high for some. The most common problems in individual trials were the inability to blind participants and investigators and outcome measures susceptible to measurement bias. The main issues leading to downgrading of the certainty of the evidence were heterogeneity of results, low precision and high or moderate risk of bias in the included trials. Publication bias could not be shown for any of the inspected analyses. In adults, psychotherapy was slightly more effective than care-as-usual (CAU) in improving short-term QoL (SMD 0.23, 95% CI 0.12 to 0.34; I2 = 13%; 20 trials, 1572 participants; moderate-certainty), depression (SMD -0.27, 95% CI -0.39 to -0.16; I2 = 0%; 16 trials, 1232 participants; moderate-certainty), and anxiety (SMD -0.29, 95% CI -0.40 to -0.17; I2 = 1%; 15 studies, 1135 participants; moderate-certainty). The results for disease activity were not pooled due to high heterogeneity (I2 = 72%). Interventions which used patient education may also have small positive short-term effects on QoL (SMD 0.19, 95% CI 0.06 to 0.32; I2 = 11%; 12 trials, 1058 participants; moderate-certainty), depression (SMD -0.22, 95% CI -0.37 to -0.07; I2 = 11%; 7 studies, 765 participants; moderate-certainty) and anxiety (SMD -0.16, 95% CI -0.32 to 0.00; I2 = 10%; 6 studies, 668 participants; moderate-certainty). We did not find an effect of education on disease activity (SMD -0.09, 95% CI -0.28 to 0.10; I2 = 38%; 7 studies, 755 participants; low-certainty). Pooled results on the effects of relaxation techniques showed small effects on QoL (SMD 0.25, 95% CI 0.08 to 0.41; I2 = 30%; 12 studies, 916 participants; moderate-certainty), depression (SMD -0.18, 95% CI -0.35 to -0.02; I2 = 0%; 7 studies, 576 participants; moderate-certainty), and anxiety (SMD -0.26, 95% CI -0.43 to -0.09; I2 = 13%; 8 studies, 627 participants; moderate-certainty). Results for disease activity were not pooled due to high heterogeneity (I2 = 72%). In children and adolescents, multimodular psychotherapy increased quality of life (SMD 0.54, 95% CI 0.06 to 1.02; I2 = 19%; 3 studies, 91 participants; moderate-certainty). The results for anxiety were inconclusive (SMD -0.09; 95% CI 0.-64 to 0.46; 2 trials, 51 patients, very low-certainty). Pooled effects were not calculated for depressive symptoms. Disease activity was not assessed in any of the trials compared to CAU. In education, based on one study, there might be a positive effect of the intervention on quality of life (MD 7.1, 95% CI 2.18 to 12.02; 40 patients; low-certainty evidence) but possibly not on depression (MD -6, 95% CI -12.01 to 0.01; 41 patients; very low-certainty). Anxiety and disease activity were not assessed for this comparison. Regarding the effects of relaxation techniques on children and adolescents, all results were inconclusive (very low-certainty). AUTHORS' CONCLUSIONS Psychological interventions in adults are likely to improve the quality of life, depression and anxiety slightly. Psychotherapy is probably also effective for improving the quality of life in children and adolescents. The evidence suggests that psychological interventions may have little to no effect on disease activity. The interpretation of these results presents a challenge due to the clinical heterogeneity of the included trials, particularly concerning the type and various components of the common multimodular interventions. This complexity underscores the need for further research and exploration in this area.
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Affiliation(s)
- Natalia Tiles-Sar
- Division of Epidemiology and Biometry, Carl von Ossietzky University of Oldenburg, Oldenburg, Germany
| | - Johanna Neuser
- Division of Epidemiology and Biometry, Carl von Ossietzky University of Oldenburg, Oldenburg, Germany
| | - Dominik de Sordi
- Division of Epidemiology and Biometry, Carl von Ossietzky University of Oldenburg, Oldenburg, Germany
| | - Anne Baltes
- The German Assocation for Crohn's Disease and Ulcerative Colitis (DCCV) e.V., Berlin, Germany
| | - Jan C Preiss
- Gastroenterologie, Diabetologie und Hepatologie, Vivantes Klinikum Neukölln, Berlin, Germany
| | - Gabriele Moser
- Clinic of Internal Medicine III, Medical University of Vienna, A-1090 Vienna, Austria
| | - Antje Timmer
- Division of Epidemiology and Biometry, Carl von Ossietzky University of Oldenburg, Oldenburg, Germany
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Kang J, Wang J, Su J, Wang W, Lu Y, Tang Z, Zou L, Yin A, Li J, Ren H, Zhou Q, Wan H, An P. Pancreatic Enzyme Replacement Therapy Improves Exclusive Enteral Nutrition Related Diarrhea in Crohn's Disease: A Prospective Randomized Trial. United European Gastroenterol J 2025. [PMID: 40243170 DOI: 10.1002/ueg2.70021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 02/21/2025] [Accepted: 03/03/2025] [Indexed: 04/18/2025] Open
Abstract
BACKGROUND & AIMS Previous results showed that combined treatment of biologics and exclusive enteral nutrition (EEN) brought moderate-to-severe Crohn's disease patients significant improvements in clinical and endoscopic outcomes. Despite its essential role and favorable safety profile, EEN in the treatment of adult Crohn's disease is frequently underestimated because of lower compliance and several side effects, including EEN-related diarrhea (EEND). METHODS In this prospective, single-center randomized clinical trial, 147 eligible patients with actively moderate-to-severe Crohn's disease treated with biologics and concomitant 16-week EEN were included. Sixty-one patients without EEND were enrolled in the ND group (without EEN-related diarrhea), and other patients with EEND who received pancreatic enzyme replacement therapy (PERT) (43 patients) or not (43 patients) were recruited in PERT and NPERT groups, respectively. The clinical outcomes, biologic outcomes, and endoscopic outcomes were evaluated. Quality of life (QoL) and psychological status were also assessed at baseline and endpoints (week 16). RESULTS Bowel movements (daily frequency decreased by 5.3 times) and stool consistency (reduced watery and loose stool) were greatly improved in PERT group at week 16. At week 16, patients in the ND and PERT groups achieved similar clinical responses (93% in ND group and 94.7% in PERT group, p = 0.731) and clinical remission (86.0% in ND group and 86.8% in PERT group, p = 0.90) while patients in the NPERT group had significantly lower proportions of these clinical outcomes (67.9% clinical response and 57.1% clinical remission). No significant difference was observed in endoscopic outcomes between each group (p = 0.904). QoL and mental status including anxiety and depression in PERT group had great improvement compared with the NPERT group. CONCLUSIONS Our prospective results provided invaluable evidence that PERT supplementation efficiently improved EEND in Crohn's disease patients with combined treatment of biologics and 16-week EEN, which had a promising effect in active Crohn's disease induction. TRIAL REGISTRATION ChiCTR2200058343.
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Affiliation(s)
- Jian Kang
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
- Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, Renmin Hospital of Wuhan University, Wuhan, China
- Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, China
| | - Jing Wang
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
- Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, Renmin Hospital of Wuhan University, Wuhan, China
- Department of Gastroenterology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China
| | - Juan Su
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
- Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, Renmin Hospital of Wuhan University, Wuhan, China
- Department of Gastroenterology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China
| | - Wei Wang
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
- Department of Gastroenterology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China
| | - Yueyue Lu
- Department of Gastroenterology, First Hospital of Yangtze University, Jingzhou, China
| | - Zhishun Tang
- School of Sports Medicine, Wuhan Sports University, Wuhan, China
| | - Liping Zou
- The Clinical Skill Center, Teaching Office of the First School of Clinical Medicine, Renmin Hospital of Wuhan University, Wuhan, China
| | - Anning Yin
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
- Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, Renmin Hospital of Wuhan University, Wuhan, China
- Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, China
| | - Jiao Li
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
- Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, Renmin Hospital of Wuhan University, Wuhan, China
- Department of Gastroenterology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China
| | - Haixia Ren
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
- Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, Renmin Hospital of Wuhan University, Wuhan, China
- Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, China
| | - Qian Zhou
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
- Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, Renmin Hospital of Wuhan University, Wuhan, China
- Department of Gastroenterology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China
| | - Huipeng Wan
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
- Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, Renmin Hospital of Wuhan University, Wuhan, China
- Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, China
| | - Ping An
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
- Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, Renmin Hospital of Wuhan University, Wuhan, China
- Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, China
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Saleh AA, Waghela R, Amini S, Moskow J, Irani M, Fan C, Glassner K, Abraham BP. A Guide to De-escalation of Combination Therapy in Inflammatory Bowel Disease: A Retrospective Cohort Study. CROHN'S & COLITIS 360 2025; 7:otaf026. [PMID: 40321837 PMCID: PMC12048838 DOI: 10.1093/crocol/otaf026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Indexed: 05/08/2025] Open
Abstract
Background Advanced combination therapy with biologics and small molecules has seen more widespread implementation for inflammatory bowel disease (IBD). However, there is a paucity of data available to guide the successful de-escalation of combination therapy following the achievement of disease remission. Therefore, we pursued this retrospective study to evaluate our center's approach to de-escalation of these patients. Methods IBD patients undergoing de-escalation of combination biologic therapy from May 2017 to March 2023 with a follow-up visit were included. The need for re-escalation, steroid therapy, and hospitalization at follow-up was compared between the de-escalation method, adherence, patient demographics, disease characteristics, and measures of disease activity. Results Fifty IBD patients underwent de-escalation, with a median age of 35.7 years. All 50 patients had a follow-up visit within a median of 168 (111) days. Patients were divided into two groups with 12 (24%) patients requiring re-escalation of therapy and 38 (76%) able to maintain or further de-escalate. Of those that required re-escalation, 3 (25%) required the use of systemic steroids and none required hospitalization for IBD. Non-adherence to the de-escalation plan significantly correlated with the need for re-escalation (P < .001). Conclusions Patient adherence and the number of prior failed biologic therapies were identified as potential risk factors for re-escalation. The type of agent being de-escalated (biologic or Janus kinase inhibitors [JAKi] did not correlate with the need for re-escalation).
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Affiliation(s)
- Adam A Saleh
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Rajdeepsingh Waghela
- Houston Methodist Hospital, Underwood Center for Digestive Diseases, Fondren Inflammatory Bowel Disease Center, Houston, TX, USA
| | - Shayan Amini
- Houston Methodist Hospital, Underwood Center for Digestive Diseases, Fondren Inflammatory Bowel Disease Center, Houston, TX, USA
| | - Joshua Moskow
- Texas A&M College of Engineering Medicine, Houston, TX, USA
| | - Malcom Irani
- Houston Methodist Hospital, Underwood Center for Digestive Diseases, Fondren Inflammatory Bowel Disease Center, Houston, TX, USA
| | - Christopher Fan
- Houston Methodist Hospital, Underwood Center for Digestive Diseases, Fondren Inflammatory Bowel Disease Center, Houston, TX, USA
| | - Kerri Glassner
- Houston Methodist Hospital, Underwood Center for Digestive Diseases, Fondren Inflammatory Bowel Disease Center, Houston, TX, USA
| | - Bincy P Abraham
- Houston Methodist Hospital, Underwood Center for Digestive Diseases, Fondren Inflammatory Bowel Disease Center, Houston, TX, USA
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Chatterjee A, Bhatia P, Sinha SK, Singh AK, Mandavdhare HS, Shah J, Jearth V, Sasani A, Sekar A, Singh M, Dutta U, Sharma V. Effectiveness and safety of thiopurines in inflammatory bowel disease patients with NUDT15 polymorphism: a real-world retrospective study. Expert Rev Clin Pharmacol 2025; 18:175-183. [PMID: 39921705 DOI: 10.1080/17512433.2025.2465425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Revised: 01/31/2025] [Accepted: 02/06/2025] [Indexed: 02/10/2025]
Abstract
BACKGROUND Thiopurine S-methyltransferase (TPMT) and Nudix hydrolase (NUDT15) polymorphisms predispose to thiopurine-related leukopenia. METHODS Retrospective evaluation of inflammatory bowel disease (IBD) patients harboring NUDT15 polymorphisms and exposed to thiopurines. We report the frequency of NUDT15 polymorphism, frequency of leukopenia, the tolerated dose of azathioprine, and the clinical efficacy of thiopurines. RESULTS Of 1440 patients, 118 (8.2%) had NUDT15 polymorphism. Among 51 with complete details, 46 were heterozygous (90.2%), and 5 homozygous (9.2%) for NUDT15. Twenty (43.5%) heterozygous and all homozygous patients developed leukopenia. Leukopenia was significantly more in NUDT15 heterozygous group compared to controls (43.45% vs 7.8%, Odds ratio: 9, 95% CI 3.57-22.9). The maximum tolerated dose of azathioprine was lower in NUDT15 heterozygous group (1.1 ± 0.4 mg per kg vs 1.7 ± 0.7 mg per kg, p = 0.002). The mean time to leukopenia was earlier in the heterozygous group vs controls (19 ± 56 weeks vs 70 ± 53 weeks, p-value 0.002). Seven (35%) of 20 heterozygous patients who developed leukopenia, could be maintained at a lower dose of thiopurine. Twenty-five maintained clinical remission while on thiopurines. CONCLUSION Thiopurines should be avoided in NUDT15 homozygous but can be used cautiously at lower dosages with frequent monitoring among heterozygous patients.
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Affiliation(s)
- Abhirup Chatterjee
- Department of Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Prateek Bhatia
- Department of Pediatric Hemato-oncology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Saroj K Sinha
- Department of Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Anupam K Singh
- Department of Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Harshal S Mandavdhare
- Department of Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Jimil Shah
- Department of Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Vaneet Jearth
- Department of Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Arpit Sasani
- Department of Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Aravind Sekar
- Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Minu Singh
- Department of Pediatric Hemato-oncology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Usha Dutta
- Department of Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Vishal Sharma
- Department of Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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Lewis JD, Vadhariya A, Su S, Zhou X, Durand F, Kawata AK, Stassek L, Clucas C, Schreiber S. A patient-reported outcome measure comprising the stool frequency and abdominal pain items from the Crohn's Disease Activity Index: psychometric evaluation in adults with Crohn's disease. J Patient Rep Outcomes 2025; 9:19. [PMID: 39962027 PMCID: PMC11833035 DOI: 10.1186/s41687-025-00851-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 02/09/2025] [Indexed: 02/20/2025] Open
Abstract
BACKGROUND The Stool Frequency (SF) and Abdominal Pain (AP) items from the Crohn's Disease Activity Index are together referred to as the "Patient Reported Outcome" (PRO). The SF item measures the number of very soft/liquid stools and the AP item measures abdominal pain severity, which are common Crohn's disease (CD) symptoms that patients consider important to treat. This study evaluated the psychometric properties of both PRO items separately and estimated thresholds for clinical remission in moderately to severely active CD. METHODS The measurement properties of the PRO items were analyzed using pooled data from VIVID-1 (NCT03926130), a Phase 3, randomized, placebo- and active-controlled study in adults with moderately to severely active CD. Analyses used weekly average scores of the SF and AP items at Weeks 0 (Baseline), 4, 12, and 52. Remission thresholds were estimated using the Patient Global Rating of Severity (PGRS) and Patient Global Impression of Change (PGIC) as primary anchors as well as qualitative evidence from exit interviews. RESULTS Data from 1065 participants (mean age: 36.2 years [standard deviation: 13 years]) were analyzed. During the trial, scores improved for both PRO items. Both items demonstrated moderate-to-good test-retest reliability for participants defined as stable based on PGRS and PGIC. Most correlations of related assessments were moderate (0.30≤|ρ| <0.70) with SF and moderate-to-large (0.30≤|ρ| ≤0.90) with AP. By contrast, as anticipated, both items had weak correlations (|ρ| <0.30) with endoscopic and laboratory assessments. The PRO items could discriminate between groups of participants known to differ based on other assessments. The PRO items were able to detect change, as score changes in both items between Baseline and Weeks 12 and 52 differed significantly between most PGRS and PGIC categories. Anchor-based analyses combined with responses from the exit interviews suggested that an SF score of ≤ 3 and an AP score of ≤ 1 could together represent clinical remission. CONCLUSION These results support the reliability, construct-validity, and responsiveness of both PRO items in moderately to severely active CD and confirm previously suggested scores for both items that could represent clinical remission. TRIAL REGISTRATION Clinicaltrials.gov, NCT03926130. Registered 23 April 2019, https://clinicaltrials.gov/study/NCT03926130 .
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Affiliation(s)
- James D Lewis
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA, USA
| | - Aisha Vadhariya
- Eli Lilly and Company, 893 S Delaware St., Indianapolis, IN, 46225, USA.
| | - Sylvia Su
- Eli Lilly and Company, 893 S Delaware St., Indianapolis, IN, 46225, USA
| | | | - Frederick Durand
- Eli Lilly and Company, 893 S Delaware St., Indianapolis, IN, 46225, USA
| | | | | | | | - Stefan Schreiber
- Department of Internal Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel, Germany
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Khan A, Azzam MA. Inflammatory Bowel Disease and Stroke: Exploring Hidden Vascular Risks. Cureus 2025; 17:e79304. [PMID: 40125129 PMCID: PMC11927930 DOI: 10.7759/cureus.79304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/19/2025] [Indexed: 03/25/2025] Open
Abstract
Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is primarily known for its gastrointestinal manifestations. However, emerging evidence suggests a potential link between IBD and an increased risk of stroke, likely mediated by chronic systemic inflammation, endothelial dysfunction, and a prothrombotic state. Despite this growing recognition, the exact mechanisms and extent of this association remain unclear, highlighting a critical knowledge gap. This review aims to systematically analyze the association between IBD and stroke, exploring the underlying vascular mechanisms and identifying potential risk factors contributing to cerebrovascular events in IBD patients. A comprehensive literature search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines across PubMed, Scopus, and Google Scholar using keywords such as "IBD," "Stroke," "Chronic inflammation," "Cerebrovascular risk," and "Gut-brain axis." After screening 150 studies and applying inclusion and exclusion criteria, six studies were included in the final synthesis. The findings suggest that chronic inflammation in IBD plays a key role in increasing stroke risk through endothelial dysfunction and a heightened prothrombotic state, with additional risk factors such as atrial fibrillation during active IBD flares further contributing to cerebrovascular events. While biologic therapies, including tumor necrosis factor (TNF)-alpha inhibitors, are effective in reducing systemic inflammation, their impact on mitigating stroke risk remains inconclusive. Given the potential role of IBD as an independent risk factor for stroke, a multidisciplinary approach to management is crucial. Addressing modifiable risk factors through pharmacologic interventions such as biologics, statins, and antiplatelet agents, alongside lifestyle modifications, could help reduce cerebrovascular complications in IBD patients. Further research is needed to explore personalized therapeutic strategies and establish clearer preventive guidelines for this at-risk population.
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Affiliation(s)
- Abdallah Khan
- Internal Medicine, RAK Medical and Health Sciences University, Ras Al Khaimah, ARE
| | - Maysoon A Azzam
- Internal Medicine, RAK Medical and Health Sciences University, Ras Al Khaimah, ARE
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Dubinsky M, Vadhariya A, Su S, Zhou X, Durand F, Clucas C, Stassek L, Kawata AK, Travis S. The Urgency Numeric Rating Scale: Psychometric Evaluation in Adults with Crohn's Disease. Adv Ther 2025; 42:1044-1060. [PMID: 39692838 PMCID: PMC11787167 DOI: 10.1007/s12325-024-03081-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Accepted: 11/22/2024] [Indexed: 12/19/2024]
Abstract
INTRODUCTION Bowel urgency has recently been recognized as a Crohn's disease (CD) symptom that substantially impacts patients' quality of life. The Urgency NRS is a single-item patient-reported outcome measure assessing bowel urgency severity in the past 24 h (0-10 scale). We aimed to evaluate the psychometric properties of the Urgency Numeric Rating Scale (NRS) in adults with moderately to severely active CD and to estimate thresholds for meaningful improvement and bowel urgency remission. METHODS Psychometric analyses used pooled data from the Phase 3 VIVID-1 study of mirikizumab, where participants with CD completed the Urgency NRS and other assessments. The Patient Global Rating of Severity (PGRS) and Patient Global Impression of Change (PGIC) were used as primary anchors to estimate Urgency NRS thresholds representing meaningful improvement and remission. RESULTS The Urgency NRS showed good test-retest reliability in participants who were stable based on PGRS and PGIC. It was moderately correlated with similar assessments and weakly correlated with endoscopic/laboratory assessments. It differentiated between participant subgroups varying in disease severity and quality of life based on PGRS and other assessments. It was sensitive to change, as Urgency NRS improvements during the trial differed between most PGRS change and PGIC categories. A 3-5-point reduction on the Urgency NRS represented meaningful improvement and a score of ≤ 2 represented remission. CONCLUSION The Urgency NRS demonstrated strong psychometric properties in the VIVID-1 population of moderately to severely active CD. Analyses also suggested meaningful improvement and remission thresholds. TRIAL REGISTRATION Clinicaltrials.gov, NCT03926130. Registered 23 April 2019, https://clinicaltrials.gov/study/NCT03926130 .
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Affiliation(s)
- Marla Dubinsky
- Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Aisha Vadhariya
- Eli Lilly and Company, 893 S Delaware St., Indianapolis, IN, 46225, USA.
| | - Sylvia Su
- Eli Lilly and Company, 893 S Delaware St., Indianapolis, IN, 46225, USA
| | | | - Frederick Durand
- Eli Lilly and Company, 893 S Delaware St., Indianapolis, IN, 46225, USA
| | | | | | | | - Simon Travis
- Kennedy Institute, Translational Gastroenterology Unit and Biomedical Research Centre, University of Oxford, Oxford, UK
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10
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Cosier D, Lambert K, Charlton K, Batterham M, Little RD, Wu N, Tavakoli P, Ghaly S, Pipicella JL, Connor S, Leach S, Lemberg DA, Houshyar Y, Jayawardana T, Koentgen S, on behalf of the Australian IBD Microbiome Study Consortium, Hold GL. Dietary Patterns and Fibre Intake Are Associated with Disease Activity in Australian Adults with Inflammatory Bowel Disease: An Exploratory Dietary Pattern Analysis. Nutrients 2024; 16:4349. [PMID: 39770970 PMCID: PMC11677955 DOI: 10.3390/nu16244349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 12/10/2024] [Accepted: 12/12/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND Few studies have explored the relationship between habitual dietary patterns and disease activity in people with Inflammatory Bowel Disease (IBD). This cross-sectional study explored the association between dietary patterns and clinical and objective markers of inflammation in adults from the Australian IBD Microbiome Study. METHODS Dietary patterns were derived using principal component analysis (PCA) of baseline food frequency questionnaire data. Food intake was quantified using 3-day food record data. Associations between dietary intake and both clinical disease activity index (CDAI) and faecal calprotectin (FCP) were analysed. RESULTS Participants included 412 adults (IBD = 223, Healthy controls (HC) = 189). Both cohorts consumed poor-quality diets with inadequate servings of most food groups compared to Australian reference standards. IBD participants without FCP inflammation had significantly higher fibre intake than those with moderate FCP. In the Crohn's Disease group, high adherence to 'High plant diversity' and 'Meat eaters' dietary patterns were associated with increased CDAI and FCP, respectively. In the combined IBD cohort, high adherence to a 'Vegan-style' dietary pattern was associated with increased FCP. CONCLUSIONS There is a need for dietary modifications among Australian adults, both with and without IBD, to improve dietary fibre intake and adherence to dietary guidelines. Dietary patterns characterised by a high intake of plant foods or meat products were both positively associated with indicators of active IBD. It is possible that some participants with active IBD were modifying their diet to try to manage their disease and reduce symptoms, contributing to the association between healthier dietary patterns and active disease. Further clinical and longitudinal studies are needed to expand upon the findings. This study offers a unique contribution by utilising FCP as an objective marker of intestinal inflammation and applying dietary pattern analysis to investigate the relationship between diet and inflammatory markers.
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Affiliation(s)
- Denelle Cosier
- School of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, NSW 2500, Australia
| | - Kelly Lambert
- School of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, NSW 2500, Australia
| | - Karen Charlton
- School of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, NSW 2500, Australia
| | - Marijka Batterham
- Statistical Consulting Centre, National Institute for Applied Statistical Research Australia, University of Wollongong, Wollongong, NSW 2500, Australia
| | - Robert D. Little
- Department of Gastroenterology, Alfred Health, Melbourne, VIC 3004, Australia
- Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC 3800, Australia
| | - Nan Wu
- University of New South Wales Microbiome Research Centre, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2033, Australia
- Department of Gastroenterology, Sutherland Hospital, Sydney, NSW 2229, Australia
| | - Paris Tavakoli
- University of New South Wales Microbiome Research Centre, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2033, Australia
| | - Simon Ghaly
- Department of Gastroenterology and Hepatology, St Vincent’s Hospital Sydney and St Vincent’s Clinical School, UNSW Medicine & Health, University of New South Wales, Sydney, NSW 2033, Australia
| | - Joseph L. Pipicella
- Department of Gastroenterology, Liverpool Hospital and South West Sydney Clinical Campuses, UNSW Medicine & Health, University of New South Wales, Sydney, NSW 2033, Australia
- Crohn’s Colitis Cure, Sydney, NSW 2009, Australia
| | - Susan Connor
- Department of Gastroenterology, Liverpool Hospital and South West Sydney Clinical Campuses, UNSW Medicine & Health, University of New South Wales, Sydney, NSW 2033, Australia
| | - Steven Leach
- Discipline of Paediatrics, School of Clinical Medicine, University of New South Wales, Sydney, NSW 2033, Australia
| | - Daniel A. Lemberg
- Discipline of Paediatrics, School of Clinical Medicine, University of New South Wales, Sydney, NSW 2033, Australia
- Department of Gastroenterology, Sydney Children’s Hospital, Sydney, NSW 2031, Australia
| | - Yashar Houshyar
- University of New South Wales Microbiome Research Centre, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2033, Australia
| | - Thisun Jayawardana
- University of New South Wales Microbiome Research Centre, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2033, Australia
| | - Sabrina Koentgen
- University of New South Wales Microbiome Research Centre, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2033, Australia
| | | | - Georgina L. Hold
- University of New South Wales Microbiome Research Centre, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2033, Australia
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11
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Cavalcanti E, Marra A, Mileti A, Donghia R, Curlo M, Mastronardi M. Nutritional Management in Stricturing Crohn's Disease: A Pilot Study. Nutrients 2024; 16:4153. [PMID: 39683547 PMCID: PMC11644502 DOI: 10.3390/nu16234153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Revised: 11/20/2024] [Accepted: 11/29/2024] [Indexed: 12/18/2024] Open
Abstract
BACKGROUND More than half of patients with Crohn's disease develop intestinal fibrosis induced intestinal obstruction with debilitating symptoms throughout their disease course. The incidence of stricture formation in CD has remained unchanged over the last several decades. Factors promoting intestinal fibrosis are currently unclear, but diet may represent an underestimated risk factor for intestinal fibrosis by modification of both the host immune response and intestinal microbial composition. Evaluating the impact of diet on the course of IBD is very complex. Sarcopenia is a common problem in IBD patients and correlates with an increased rate of disease. Skeletal muscle index (SMI) is an important parameter to measure sarcopenia and is an easily accessible tool for evaluating the likelihood of complications in individuals with CD. METHODS Using a randomized and controlled pilot design, we aimed to investigate the efficacy of 12 months of short-term dietary intervention based on essential amino acid (EAA) and sodium butyrate (NaB) supplementation in the management of stricturing Crohn's disease patients. RESULTS After the treatment in the diet EAA/NaB group, we revealed a statistically significant improvement of muscle mass (61.49 ± 5.47 vs. control 86 ± 10.70, p = 0.01) and SMI index (9.97 ± 1.79 vs. control 7.60 ± 2.29, p = 0.02). In addition, the measurement of skeletal muscle mass in CD patients has been suggested to be crucial for predicting the disease course. Indeed, after one year, surgery was required in 4/10 control group patients (40%) and 1/10 study group (10%) patients, underlining the importance of body composition alterations and adequate dietary intake in the management of these patients. CONCLUSIONS Further prospective studies are needed to confirm these results; nonetheless this nutritional approach could become an integral part in the treatment of stricturing CD patients to improve disease outcomes and increase the quality of life in these patients.
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Affiliation(s)
- Elisabetta Cavalcanti
- IBD Unit, National Institute of Gastroenterology-IRCCS, 70013 Castellana Grotte, Italy; (A.M.); (A.M.); (M.C.); (M.M.)
| | - Antonella Marra
- IBD Unit, National Institute of Gastroenterology-IRCCS, 70013 Castellana Grotte, Italy; (A.M.); (A.M.); (M.C.); (M.M.)
| | - Alessia Mileti
- IBD Unit, National Institute of Gastroenterology-IRCCS, 70013 Castellana Grotte, Italy; (A.M.); (A.M.); (M.C.); (M.M.)
| | - Rossella Donghia
- Data Science Unit, National Institute of Gastroenterology-IRCCS, 70013 Castellana Grotte, Italy;
| | - Margherita Curlo
- IBD Unit, National Institute of Gastroenterology-IRCCS, 70013 Castellana Grotte, Italy; (A.M.); (A.M.); (M.C.); (M.M.)
| | - Mauro Mastronardi
- IBD Unit, National Institute of Gastroenterology-IRCCS, 70013 Castellana Grotte, Italy; (A.M.); (A.M.); (M.C.); (M.M.)
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Wohl P, Krausova A, Wohl P, Fabian O, Bajer L, Brezina J, Drastich P, Hlavaty M, Novotna P, Kahle M, Spicak J, Gregor M. Limited validity of Mayo endoscopic subscore in ulcerative colitis with concomitant primary sclerosing cholangitis. World J Gastrointest Endosc 2024; 16:607-616. [PMID: 39600557 PMCID: PMC11586720 DOI: 10.4253/wjge.v16.i11.607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 09/13/2024] [Accepted: 10/09/2024] [Indexed: 10/30/2024] Open
Abstract
BACKGROUND Ulcerative colitis (UC) with concomitant primary sclerosing cholangitis (PSC) represents a distinct disease entity (PSC-UC). Mayo endoscopic subscore (MES) is a standard tool for assessing disease activity in UC but its relevance in PSC-UC remains unclear. AIM To assess the accuracy of MES in UC and PSC-UC patients, we performed histological scoring using Nancy histological index (NHI). METHODS MES was assessed in 30 PSC-UC and 29 UC adult patients during endoscopy. NHI and inflammation were evaluated in biopsies from the cecum, rectum, and terminal ileum. In addition, perinuclear anti-neutrophil cytoplasmic antibodies, fecal calprotectin, body mass index, and other relevant clinical characteristics were collected. RESULTS The median MES and NHI were similar for UC patients (MES grade 2 and NHI grade 2 in the rectum) but were different for PSC-UC patients (MES grade 0 and NHI grade 2 in the cecum). There was a correlation between MES and NHI for UC patients (Spearman's r = 0.40, P = 0.029) but not for PSC-UC patients. Histopathological examination revealed persistent microscopic inflammation in 88% of PSC-UC patients with MES grade 0 (46% of all PSC-UC patients). Moreover, MES overestimated the severity of active inflammation in an additional 11% of PSC-UC patients. CONCLUSION MES insufficiently identifies microscopic inflammation in PSC-UC. This indicates that histological evaluation should become a routine procedure of the diagnostic and grading system in both PSC-UC and PSC.
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Affiliation(s)
- Pavel Wohl
- Department of Gastroenterology, Institute for Clinical and Experimental Medicine, Prague 14021, Czech Republic
| | - Alzbeta Krausova
- Department of Integrative Biology, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague 14220, Czech Republic
| | - Petr Wohl
- Department of Metabolism and Diabetes, Institute for Clinical and Experimental Medicine, Prague 14021, Czech Republic
| | - Ondrej Fabian
- Clinical and Transplant Pathology Centre, Institute for Clinical and Experimental Medicine, Prague 14021, Czech Republic
| | - Lukas Bajer
- Department of Gastroenterology, Institute for Clinical and Experimental Medicine, Prague 14021, Czech Republic
| | - Jan Brezina
- Department of Gastroenterology, Institute for Clinical and Experimental Medicine, Prague 14021, Czech Republic
| | - Pavel Drastich
- Department of Gastroenterology, Institute for Clinical and Experimental Medicine, Prague 14021, Czech Republic
| | - Mojmir Hlavaty
- Department of Gastroenterology, Institute for Clinical and Experimental Medicine, Prague 14021, Czech Republic
| | - Petra Novotna
- Department of Integrative Biology, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague 14220, Czech Republic
| | - Michal Kahle
- Department of Data Analysis, Statistics and Artificial Intelligence, Institute for Clinical and Experimental Medicine, Prague 14021, Czech Republic
| | - Julius Spicak
- Department of Gastroenterology, Institute for Clinical and Experimental Medicine, Prague 14021, Czech Republic
| | - Martin Gregor
- Department of Integrative Biology, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague 14220, Czech Republic
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Swaminathan A, Day AS, Sparrow MP, Peyrin-Biroulet L, Siegel CA, Gearry RB. Review article: Measuring disease severity in inflammatory bowel disease - Beyond treat to target. Aliment Pharmacol Ther 2024; 60:1176-1199. [PMID: 39403053 DOI: 10.1111/apt.18231] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Revised: 08/07/2024] [Accepted: 08/18/2024] [Indexed: 01/11/2025]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) follows a heterogenous disease course and predicting a patient's prognosis is challenging. There is a wide burden of illness in IBD and existing tools measure disease activity at a snapshot in time. Comprehensive assessment of IBD severity should incorporate disease activity, prognosis, and the impacts of disease on a patient. This review investigates the concept of disease severity in adults with IBD to highlight key components contributing to this. METHODS To perform this narrative review, a Medline search was conducted for full-text articles available at 1st March 2024 using search terms which encompassed disease activity assessment, disease severity, prognosis, natural history of Crohn's disease (CD) and ulcerative colitis (UC), and the burden of IBD. RESULTS Current methods of disease assessment in IBD have evolved from a focus on the burden of symptoms to one that includes inflammatory targets, genetic, serological, and proteomic profiles, and assessments of quality-of-life (QoL), disability, and psychosocial health. Longitudinal studies of IBD suggest that the burden of illness is driven by disease phenotype, clinical markers of complicated disease course (previous intestinal resection, corticosteroid use, perianal disease in CD, recent hospitalisations in UC), gut inflammation, and the impact of IBD on the patient. CONCLUSIONS Disease severity in IBD can be difficult to conceptualise due to the multitude of factors that contribute to IBD outcomes. Measurement of IBD severity may better encapsulate the full burden of illness rather than gut inflammation alone at a single timepoint and may be associated with longitudinal outcomes.
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Affiliation(s)
- Akhilesh Swaminathan
- Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand
- Department of Gastroenterology, Christchurch Hospital, Christchurch, New Zealand
| | - Andrew S Day
- Department of Paediatrics, University of Otago Christchurch, Christchurch, New Zealand
| | - Miles P Sparrow
- Department of Gastroenterology, Alfred Health and School of Translational Medicine, Monash University, Australia
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, Vandoevre-les-Nancy, France
- Department of Gastroenterology, INFINY Institute, FHU-CURE, INSERM NGERE, Nancy University Hospital, Vandoeuvre-les-Nancy, France
- Groupe Hospitalier privé Ambroise Paré - Hartmann, Paris IBD Center, Neuilly sur Seine, France
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Corey A Siegel
- Center for Digestive Health, Section of Gastroenterology and Hepatology, Dartmouth Hitchcock Medical Centre, Lebanon, New Hampshire, USA
| | - Richard B Gearry
- Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand
- Department of Gastroenterology, Christchurch Hospital, Christchurch, New Zealand
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14
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Winders S, Yoo L, Heitkemper M, Kamp K. Multilevel Factors and Sleep in Adults With Inflammatory Bowel Disease: A Qualitative Study. CROHN'S & COLITIS 360 2024; 6:otae075. [PMID: 39691468 PMCID: PMC11649995 DOI: 10.1093/crocol/otae075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Indexed: 12/19/2024] Open
Abstract
Background This study aimed to describe the patient-reported factors that impact sleep among individuals with inflammatory bowel disease (IBD), aligning with the Social Ecological Model of Sleep. This addresses the gap in IBD sleep research, which predominantly focuses on individual-level factors and their impact on sleep. Methods Adults (ages 18-65) with IBD were recruited online through ResearchMatch in June 2023. Participants filled out survey questions on their demographic characteristics, health history, sleep, and IBD-related symptoms. Content analysis was conducted on 2 open-ended questions about factors that impacted their sleep. Results This analysis included 163 adults with IBD (M = 39 years of age, 76.7% White, 91.4% non-Hispanic or Latino, 66.9% female, and 83.4% active IBD) who answered open-ended questions with comments about their sleep. Most participants indicated an individual-level factor impacted their sleep quality (85.3%, n = 139), categorized into 5 subthemes: Mental health, health, behavior and choices, physiology, and attitudes. Additionally, participants (43.6%, n = 71) mentioned social-level factors divided into 7 subthemes: Family, work, home, neighborhood, social network, and school. A smaller group of participants (17.2%, n = 28) mentioned societal-level factors designated into 4 subthemes: Natural environment and geography, technology, 24/7 society, and economics. Conclusions This study highlights the need for tailored sleep interventions for those with IBD that consider not only disease activity but also mental health, family, work, and the natural environment. IBD clinics should prioritize sleep health using an interdisciplinary approach to holistically address the unique needs of those with IBD.
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Affiliation(s)
- Samantha Winders
- Department of Biobehavioral Nursing and Health Informatics, University of Washington School of Nursing, Seattle, WA, USA
| | - Linda Yoo
- Department of Biobehavioral Nursing and Health Informatics, University of Washington School of Nursing, Seattle, WA, USA
| | - Margaret Heitkemper
- Department of Biobehavioral Nursing and Health Informatics, University of Washington School of Nursing, Seattle, WA, USA
| | - Kendra Kamp
- Department of Biobehavioral Nursing and Health Informatics, University of Washington School of Nursing, Seattle, WA, USA
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Sands BE, Panés J, Feagan BG, Zhang H, Vetter ML, Mathias SD, Huang KHG, Johanns J, Germinaro M, Sahoo A, Terry NA, Han C. Qualitative and Psychometric Evaluation of 29-Item Patient-Reported Outcomes Measurement Information System® to Assess General Health-Related Quality of Life in Patients With Moderately to Severely Active Inflammatory Bowel Disease. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2024; 27:1225-1234. [PMID: 38843977 DOI: 10.1016/j.jval.2024.05.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 04/22/2024] [Accepted: 05/15/2024] [Indexed: 07/01/2024]
Abstract
OBJECTIVES To evaluate content validity and psychometric properties of the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29) to determine its suitability in inflammatory bowel disease (IBD) clinical trials. METHODS Content validity of PROMIS-29 was evaluated using qualitative interviews, including concept elicitation and cognitive debriefing, among patients living with Crohn's disease (Crohn's disease n = 20) or ulcerative colitis (UC, n = 19). PROMIS-29 validity, reliability, and responsiveness were assessed using data from phase II clinical trials of Crohn's disease (N = 360) and UC (N = 518). RESULTS Common (≥74%) symptoms reported in qualitative interviews were increased stool frequency, fatigue, abdominal pain/cramping, blood/mucus in stool, bowel urgency, and diarrhea. Disease impact aligned with PROMIS-29 content (depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, and ability to participate in social roles/activities). Cognitive debriefing indicated that PROMIS-29 instructions were easily understood, items were relevant, and the recall period was appropriate. Psychometric evaluations demonstrated that PROMIS-29 scores indicating worse symptoms/functioning were associated with lower health-related quality of life and greater disease activity and severity. PROMIS-29 domain scores correlated (rs ≥ 0.40) with IBD Questionnaire domains and EuroQol-5-Dimension-5-Level dimensions measuring similar concepts. Test-retest reliability among patients with stable disease was moderate-to-excellent (0.64-0.94) for nearly all domains in all studies. PROMIS-29 was responsive to change in disease status from baseline to week 12. Thresholds for clinically meaningful improvement ranged from ≥3 to ≥8, depending on domain. CONCLUSIONS PROMIS-29 is valid, reliable, and responsive for assessing general health-related quality of life and treatment response in IBD clinical trials.
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Affiliation(s)
- Bruce E Sands
- Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Julian Panés
- Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
| | - Brian G Feagan
- Western University and Alimentiv Inc, London, ON, Canada
| | - Hongyan Zhang
- Janssen Research and Development, LLC, Spring House, PA, USA
| | - Marion L Vetter
- Janssen Research and Development, LLC, Spring House, PA, USA
| | | | | | - Jewel Johanns
- Janssen Research and Development, LLC, Spring House, PA, USA
| | | | - Aparna Sahoo
- Janssen Research and Development, LLC, Spring House, PA, USA
| | - Natalie A Terry
- Janssen Research and Development, LLC, Spring House, PA, USA
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Peyrin-Biroulet L, Chapman JC, Colombel JF, Caprioli F, D'Haens G, Ferrante M, Schreiber S, Atreya R, Danese S, Lindsay JO, Bossuyt P, Siegmund B, Irving PM, Panaccione R, Cao Q, Neimark E, Wallace K, Anschutz T, Kligys K, Duan WR, Pivorunas V, Huang X, Berg S, Shu L, Dubinsky M. Risankizumab versus Ustekinumab for Moderate-to-Severe Crohn's Disease. N Engl J Med 2024; 391:213-223. [PMID: 39018531 DOI: 10.1056/nejmoa2314585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/19/2024]
Abstract
BACKGROUND The efficacy and safety of risankizumab as compared with ustekinumab in patients with Crohn's disease are unknown. METHODS In this phase 3b, multicenter, open-label, randomized, controlled trial with blinded assessment of end points, patients with moderate-to-severe Crohn's disease who had had an inadequate response to anti-tumor necrosis factor (TNF) therapy or unacceptable side effects with such therapy were randomly assigned to receive risankizumab or ustekinumab at standard doses for 48 weeks. The two primary end points, which were tested sequentially, were clinical remission at week 24 (defined as a Crohn's Disease Activity Index score of <150 [range, 0 to 600, with higher scores indicating more severe disease activity]), which was analyzed in the first 50% of patients to complete the week 24 visit, with a noninferiority margin of 10 percentage points; and endoscopic remission at week 48 (defined as a score of ≤4, a decrease of ≥2 points from baseline, and no subscore >1 in any individual variable on the Simple Endoscopic Score for Crohn's Disease [range, 0 to 56, with higher scores indicating more severe disease]), which was analyzed for superiority in 100% of the patients. Safety was assessed in all patients who received at least one dose of risankizumab or ustekinumab. RESULTS In the full intention-to-treat population for the efficacy analysis, 230 of 255 patients (90.2%) who received risankizumab and 193 of 265 patients (72.8%) who received ustekinumab completed all the assigned treatments. Both primary end points were met; risankizumab was noninferior to ustekinumab with respect to clinical remission at week 24 (58.6% vs. 39.5%; adjusted difference, 18.4 percentage points; 95% confidence interval [CI], 6.6 to 30.3) and superior to ustekinumab with respect to endoscopic remission at week 48 (31.8% vs. 16.2%; adjusted difference, 15.6 percentage points; 95% CI, 8.4 to 22.9; P<0.001). The incidence of adverse events appeared to be similar in the two groups. CONCLUSIONS In this head-to-head clinical trial of risankizumab and ustekinumab involving patients with moderate-to-severe Crohn's disease who had had unacceptable side effects with anti-TNF therapy or an inadequate response to such therapy, risankizumab was noninferior to ustekinumab with respect to clinical remission at week 24 and superior with respect to endoscopic remission at week 48. (Funded by AbbVie; ClinicalTrials.gov number, NCT04524611.).
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Affiliation(s)
- Laurent Peyrin-Biroulet
- From the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal (L.P.-B.), and the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB (R.P.) - both in Canada; the Crohn's and Colitis Center at the Baton Rouge General and the GI Alliance, Baton Rouge, LA (J.C.C.); the Henry D. Janowitz Division of Gastroenterology, Department of Medicine (J.-F.C.), and the Susan and Leonard Feinstein IBD Center (M.D.), Icahn School of Medicine at Mount Sinai, New York; the Department of Pathophysiology and Transplantation, Università degli Studi di Milano and the Unit of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano (F.C.), and Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele (S.D.) - both in Milan; the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven (M.F.), and the Imelda GI Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden (P.B.) - both in Belgium; the Department of Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel (S.S.), the Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (R.A.), and the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin (B.S.) - all in Germany; the Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (J.O.L.), the Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust (P.M.I.), and the School of Immunology and Microbial Sciences, King's College London (P.M.I.) - all in London; the Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Q.C.); and AbbVie, North Chicago, IL (E.N., K.W., T.A., K.K., W.R.D., V.P., X.H., S.B., L.S.)
| | - J Casey Chapman
- From the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal (L.P.-B.), and the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB (R.P.) - both in Canada; the Crohn's and Colitis Center at the Baton Rouge General and the GI Alliance, Baton Rouge, LA (J.C.C.); the Henry D. Janowitz Division of Gastroenterology, Department of Medicine (J.-F.C.), and the Susan and Leonard Feinstein IBD Center (M.D.), Icahn School of Medicine at Mount Sinai, New York; the Department of Pathophysiology and Transplantation, Università degli Studi di Milano and the Unit of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano (F.C.), and Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele (S.D.) - both in Milan; the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven (M.F.), and the Imelda GI Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden (P.B.) - both in Belgium; the Department of Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel (S.S.), the Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (R.A.), and the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin (B.S.) - all in Germany; the Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (J.O.L.), the Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust (P.M.I.), and the School of Immunology and Microbial Sciences, King's College London (P.M.I.) - all in London; the Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Q.C.); and AbbVie, North Chicago, IL (E.N., K.W., T.A., K.K., W.R.D., V.P., X.H., S.B., L.S.)
| | - Jean-Frederic Colombel
- From the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal (L.P.-B.), and the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB (R.P.) - both in Canada; the Crohn's and Colitis Center at the Baton Rouge General and the GI Alliance, Baton Rouge, LA (J.C.C.); the Henry D. Janowitz Division of Gastroenterology, Department of Medicine (J.-F.C.), and the Susan and Leonard Feinstein IBD Center (M.D.), Icahn School of Medicine at Mount Sinai, New York; the Department of Pathophysiology and Transplantation, Università degli Studi di Milano and the Unit of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano (F.C.), and Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele (S.D.) - both in Milan; the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven (M.F.), and the Imelda GI Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden (P.B.) - both in Belgium; the Department of Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel (S.S.), the Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (R.A.), and the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin (B.S.) - all in Germany; the Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (J.O.L.), the Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust (P.M.I.), and the School of Immunology and Microbial Sciences, King's College London (P.M.I.) - all in London; the Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Q.C.); and AbbVie, North Chicago, IL (E.N., K.W., T.A., K.K., W.R.D., V.P., X.H., S.B., L.S.)
| | - Flavio Caprioli
- From the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal (L.P.-B.), and the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB (R.P.) - both in Canada; the Crohn's and Colitis Center at the Baton Rouge General and the GI Alliance, Baton Rouge, LA (J.C.C.); the Henry D. Janowitz Division of Gastroenterology, Department of Medicine (J.-F.C.), and the Susan and Leonard Feinstein IBD Center (M.D.), Icahn School of Medicine at Mount Sinai, New York; the Department of Pathophysiology and Transplantation, Università degli Studi di Milano and the Unit of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano (F.C.), and Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele (S.D.) - both in Milan; the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven (M.F.), and the Imelda GI Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden (P.B.) - both in Belgium; the Department of Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel (S.S.), the Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (R.A.), and the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin (B.S.) - all in Germany; the Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (J.O.L.), the Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust (P.M.I.), and the School of Immunology and Microbial Sciences, King's College London (P.M.I.) - all in London; the Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Q.C.); and AbbVie, North Chicago, IL (E.N., K.W., T.A., K.K., W.R.D., V.P., X.H., S.B., L.S.)
| | - Geert D'Haens
- From the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal (L.P.-B.), and the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB (R.P.) - both in Canada; the Crohn's and Colitis Center at the Baton Rouge General and the GI Alliance, Baton Rouge, LA (J.C.C.); the Henry D. Janowitz Division of Gastroenterology, Department of Medicine (J.-F.C.), and the Susan and Leonard Feinstein IBD Center (M.D.), Icahn School of Medicine at Mount Sinai, New York; the Department of Pathophysiology and Transplantation, Università degli Studi di Milano and the Unit of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano (F.C.), and Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele (S.D.) - both in Milan; the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven (M.F.), and the Imelda GI Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden (P.B.) - both in Belgium; the Department of Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel (S.S.), the Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (R.A.), and the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin (B.S.) - all in Germany; the Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (J.O.L.), the Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust (P.M.I.), and the School of Immunology and Microbial Sciences, King's College London (P.M.I.) - all in London; the Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Q.C.); and AbbVie, North Chicago, IL (E.N., K.W., T.A., K.K., W.R.D., V.P., X.H., S.B., L.S.)
| | - Marc Ferrante
- From the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal (L.P.-B.), and the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB (R.P.) - both in Canada; the Crohn's and Colitis Center at the Baton Rouge General and the GI Alliance, Baton Rouge, LA (J.C.C.); the Henry D. Janowitz Division of Gastroenterology, Department of Medicine (J.-F.C.), and the Susan and Leonard Feinstein IBD Center (M.D.), Icahn School of Medicine at Mount Sinai, New York; the Department of Pathophysiology and Transplantation, Università degli Studi di Milano and the Unit of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano (F.C.), and Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele (S.D.) - both in Milan; the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven (M.F.), and the Imelda GI Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden (P.B.) - both in Belgium; the Department of Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel (S.S.), the Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (R.A.), and the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin (B.S.) - all in Germany; the Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (J.O.L.), the Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust (P.M.I.), and the School of Immunology and Microbial Sciences, King's College London (P.M.I.) - all in London; the Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Q.C.); and AbbVie, North Chicago, IL (E.N., K.W., T.A., K.K., W.R.D., V.P., X.H., S.B., L.S.)
| | - Stefan Schreiber
- From the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal (L.P.-B.), and the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB (R.P.) - both in Canada; the Crohn's and Colitis Center at the Baton Rouge General and the GI Alliance, Baton Rouge, LA (J.C.C.); the Henry D. Janowitz Division of Gastroenterology, Department of Medicine (J.-F.C.), and the Susan and Leonard Feinstein IBD Center (M.D.), Icahn School of Medicine at Mount Sinai, New York; the Department of Pathophysiology and Transplantation, Università degli Studi di Milano and the Unit of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano (F.C.), and Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele (S.D.) - both in Milan; the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven (M.F.), and the Imelda GI Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden (P.B.) - both in Belgium; the Department of Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel (S.S.), the Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (R.A.), and the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin (B.S.) - all in Germany; the Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (J.O.L.), the Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust (P.M.I.), and the School of Immunology and Microbial Sciences, King's College London (P.M.I.) - all in London; the Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Q.C.); and AbbVie, North Chicago, IL (E.N., K.W., T.A., K.K., W.R.D., V.P., X.H., S.B., L.S.)
| | - Raja Atreya
- From the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal (L.P.-B.), and the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB (R.P.) - both in Canada; the Crohn's and Colitis Center at the Baton Rouge General and the GI Alliance, Baton Rouge, LA (J.C.C.); the Henry D. Janowitz Division of Gastroenterology, Department of Medicine (J.-F.C.), and the Susan and Leonard Feinstein IBD Center (M.D.), Icahn School of Medicine at Mount Sinai, New York; the Department of Pathophysiology and Transplantation, Università degli Studi di Milano and the Unit of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano (F.C.), and Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele (S.D.) - both in Milan; the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven (M.F.), and the Imelda GI Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden (P.B.) - both in Belgium; the Department of Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel (S.S.), the Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (R.A.), and the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin (B.S.) - all in Germany; the Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (J.O.L.), the Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust (P.M.I.), and the School of Immunology and Microbial Sciences, King's College London (P.M.I.) - all in London; the Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Q.C.); and AbbVie, North Chicago, IL (E.N., K.W., T.A., K.K., W.R.D., V.P., X.H., S.B., L.S.)
| | - Silvio Danese
- From the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal (L.P.-B.), and the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB (R.P.) - both in Canada; the Crohn's and Colitis Center at the Baton Rouge General and the GI Alliance, Baton Rouge, LA (J.C.C.); the Henry D. Janowitz Division of Gastroenterology, Department of Medicine (J.-F.C.), and the Susan and Leonard Feinstein IBD Center (M.D.), Icahn School of Medicine at Mount Sinai, New York; the Department of Pathophysiology and Transplantation, Università degli Studi di Milano and the Unit of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano (F.C.), and Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele (S.D.) - both in Milan; the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven (M.F.), and the Imelda GI Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden (P.B.) - both in Belgium; the Department of Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel (S.S.), the Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (R.A.), and the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin (B.S.) - all in Germany; the Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (J.O.L.), the Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust (P.M.I.), and the School of Immunology and Microbial Sciences, King's College London (P.M.I.) - all in London; the Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Q.C.); and AbbVie, North Chicago, IL (E.N., K.W., T.A., K.K., W.R.D., V.P., X.H., S.B., L.S.)
| | - James O Lindsay
- From the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal (L.P.-B.), and the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB (R.P.) - both in Canada; the Crohn's and Colitis Center at the Baton Rouge General and the GI Alliance, Baton Rouge, LA (J.C.C.); the Henry D. Janowitz Division of Gastroenterology, Department of Medicine (J.-F.C.), and the Susan and Leonard Feinstein IBD Center (M.D.), Icahn School of Medicine at Mount Sinai, New York; the Department of Pathophysiology and Transplantation, Università degli Studi di Milano and the Unit of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano (F.C.), and Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele (S.D.) - both in Milan; the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven (M.F.), and the Imelda GI Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden (P.B.) - both in Belgium; the Department of Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel (S.S.), the Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (R.A.), and the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin (B.S.) - all in Germany; the Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (J.O.L.), the Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust (P.M.I.), and the School of Immunology and Microbial Sciences, King's College London (P.M.I.) - all in London; the Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Q.C.); and AbbVie, North Chicago, IL (E.N., K.W., T.A., K.K., W.R.D., V.P., X.H., S.B., L.S.)
| | - Peter Bossuyt
- From the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal (L.P.-B.), and the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB (R.P.) - both in Canada; the Crohn's and Colitis Center at the Baton Rouge General and the GI Alliance, Baton Rouge, LA (J.C.C.); the Henry D. Janowitz Division of Gastroenterology, Department of Medicine (J.-F.C.), and the Susan and Leonard Feinstein IBD Center (M.D.), Icahn School of Medicine at Mount Sinai, New York; the Department of Pathophysiology and Transplantation, Università degli Studi di Milano and the Unit of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano (F.C.), and Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele (S.D.) - both in Milan; the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven (M.F.), and the Imelda GI Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden (P.B.) - both in Belgium; the Department of Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel (S.S.), the Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (R.A.), and the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin (B.S.) - all in Germany; the Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (J.O.L.), the Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust (P.M.I.), and the School of Immunology and Microbial Sciences, King's College London (P.M.I.) - all in London; the Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Q.C.); and AbbVie, North Chicago, IL (E.N., K.W., T.A., K.K., W.R.D., V.P., X.H., S.B., L.S.)
| | - Britta Siegmund
- From the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal (L.P.-B.), and the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB (R.P.) - both in Canada; the Crohn's and Colitis Center at the Baton Rouge General and the GI Alliance, Baton Rouge, LA (J.C.C.); the Henry D. Janowitz Division of Gastroenterology, Department of Medicine (J.-F.C.), and the Susan and Leonard Feinstein IBD Center (M.D.), Icahn School of Medicine at Mount Sinai, New York; the Department of Pathophysiology and Transplantation, Università degli Studi di Milano and the Unit of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano (F.C.), and Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele (S.D.) - both in Milan; the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven (M.F.), and the Imelda GI Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden (P.B.) - both in Belgium; the Department of Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel (S.S.), the Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (R.A.), and the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin (B.S.) - all in Germany; the Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (J.O.L.), the Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust (P.M.I.), and the School of Immunology and Microbial Sciences, King's College London (P.M.I.) - all in London; the Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Q.C.); and AbbVie, North Chicago, IL (E.N., K.W., T.A., K.K., W.R.D., V.P., X.H., S.B., L.S.)
| | - Peter M Irving
- From the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal (L.P.-B.), and the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB (R.P.) - both in Canada; the Crohn's and Colitis Center at the Baton Rouge General and the GI Alliance, Baton Rouge, LA (J.C.C.); the Henry D. Janowitz Division of Gastroenterology, Department of Medicine (J.-F.C.), and the Susan and Leonard Feinstein IBD Center (M.D.), Icahn School of Medicine at Mount Sinai, New York; the Department of Pathophysiology and Transplantation, Università degli Studi di Milano and the Unit of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano (F.C.), and Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele (S.D.) - both in Milan; the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven (M.F.), and the Imelda GI Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden (P.B.) - both in Belgium; the Department of Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel (S.S.), the Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (R.A.), and the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin (B.S.) - all in Germany; the Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (J.O.L.), the Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust (P.M.I.), and the School of Immunology and Microbial Sciences, King's College London (P.M.I.) - all in London; the Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Q.C.); and AbbVie, North Chicago, IL (E.N., K.W., T.A., K.K., W.R.D., V.P., X.H., S.B., L.S.)
| | - Remo Panaccione
- From the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal (L.P.-B.), and the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB (R.P.) - both in Canada; the Crohn's and Colitis Center at the Baton Rouge General and the GI Alliance, Baton Rouge, LA (J.C.C.); the Henry D. Janowitz Division of Gastroenterology, Department of Medicine (J.-F.C.), and the Susan and Leonard Feinstein IBD Center (M.D.), Icahn School of Medicine at Mount Sinai, New York; the Department of Pathophysiology and Transplantation, Università degli Studi di Milano and the Unit of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano (F.C.), and Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele (S.D.) - both in Milan; the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven (M.F.), and the Imelda GI Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden (P.B.) - both in Belgium; the Department of Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel (S.S.), the Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (R.A.), and the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin (B.S.) - all in Germany; the Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (J.O.L.), the Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust (P.M.I.), and the School of Immunology and Microbial Sciences, King's College London (P.M.I.) - all in London; the Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Q.C.); and AbbVie, North Chicago, IL (E.N., K.W., T.A., K.K., W.R.D., V.P., X.H., S.B., L.S.)
| | - Qian Cao
- From the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal (L.P.-B.), and the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB (R.P.) - both in Canada; the Crohn's and Colitis Center at the Baton Rouge General and the GI Alliance, Baton Rouge, LA (J.C.C.); the Henry D. Janowitz Division of Gastroenterology, Department of Medicine (J.-F.C.), and the Susan and Leonard Feinstein IBD Center (M.D.), Icahn School of Medicine at Mount Sinai, New York; the Department of Pathophysiology and Transplantation, Università degli Studi di Milano and the Unit of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano (F.C.), and Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele (S.D.) - both in Milan; the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven (M.F.), and the Imelda GI Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden (P.B.) - both in Belgium; the Department of Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel (S.S.), the Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (R.A.), and the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin (B.S.) - all in Germany; the Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (J.O.L.), the Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust (P.M.I.), and the School of Immunology and Microbial Sciences, King's College London (P.M.I.) - all in London; the Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Q.C.); and AbbVie, North Chicago, IL (E.N., K.W., T.A., K.K., W.R.D., V.P., X.H., S.B., L.S.)
| | - Ezequiel Neimark
- From the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal (L.P.-B.), and the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB (R.P.) - both in Canada; the Crohn's and Colitis Center at the Baton Rouge General and the GI Alliance, Baton Rouge, LA (J.C.C.); the Henry D. Janowitz Division of Gastroenterology, Department of Medicine (J.-F.C.), and the Susan and Leonard Feinstein IBD Center (M.D.), Icahn School of Medicine at Mount Sinai, New York; the Department of Pathophysiology and Transplantation, Università degli Studi di Milano and the Unit of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano (F.C.), and Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele (S.D.) - both in Milan; the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven (M.F.), and the Imelda GI Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden (P.B.) - both in Belgium; the Department of Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel (S.S.), the Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (R.A.), and the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin (B.S.) - all in Germany; the Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (J.O.L.), the Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust (P.M.I.), and the School of Immunology and Microbial Sciences, King's College London (P.M.I.) - all in London; the Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Q.C.); and AbbVie, North Chicago, IL (E.N., K.W., T.A., K.K., W.R.D., V.P., X.H., S.B., L.S.)
| | - Kori Wallace
- From the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal (L.P.-B.), and the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB (R.P.) - both in Canada; the Crohn's and Colitis Center at the Baton Rouge General and the GI Alliance, Baton Rouge, LA (J.C.C.); the Henry D. Janowitz Division of Gastroenterology, Department of Medicine (J.-F.C.), and the Susan and Leonard Feinstein IBD Center (M.D.), Icahn School of Medicine at Mount Sinai, New York; the Department of Pathophysiology and Transplantation, Università degli Studi di Milano and the Unit of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano (F.C.), and Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele (S.D.) - both in Milan; the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven (M.F.), and the Imelda GI Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden (P.B.) - both in Belgium; the Department of Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel (S.S.), the Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (R.A.), and the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin (B.S.) - all in Germany; the Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (J.O.L.), the Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust (P.M.I.), and the School of Immunology and Microbial Sciences, King's College London (P.M.I.) - all in London; the Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Q.C.); and AbbVie, North Chicago, IL (E.N., K.W., T.A., K.K., W.R.D., V.P., X.H., S.B., L.S.)
| | - Toni Anschutz
- From the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal (L.P.-B.), and the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB (R.P.) - both in Canada; the Crohn's and Colitis Center at the Baton Rouge General and the GI Alliance, Baton Rouge, LA (J.C.C.); the Henry D. Janowitz Division of Gastroenterology, Department of Medicine (J.-F.C.), and the Susan and Leonard Feinstein IBD Center (M.D.), Icahn School of Medicine at Mount Sinai, New York; the Department of Pathophysiology and Transplantation, Università degli Studi di Milano and the Unit of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano (F.C.), and Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele (S.D.) - both in Milan; the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven (M.F.), and the Imelda GI Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden (P.B.) - both in Belgium; the Department of Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel (S.S.), the Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (R.A.), and the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin (B.S.) - all in Germany; the Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (J.O.L.), the Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust (P.M.I.), and the School of Immunology and Microbial Sciences, King's College London (P.M.I.) - all in London; the Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Q.C.); and AbbVie, North Chicago, IL (E.N., K.W., T.A., K.K., W.R.D., V.P., X.H., S.B., L.S.)
| | - Kristina Kligys
- From the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal (L.P.-B.), and the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB (R.P.) - both in Canada; the Crohn's and Colitis Center at the Baton Rouge General and the GI Alliance, Baton Rouge, LA (J.C.C.); the Henry D. Janowitz Division of Gastroenterology, Department of Medicine (J.-F.C.), and the Susan and Leonard Feinstein IBD Center (M.D.), Icahn School of Medicine at Mount Sinai, New York; the Department of Pathophysiology and Transplantation, Università degli Studi di Milano and the Unit of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano (F.C.), and Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele (S.D.) - both in Milan; the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven (M.F.), and the Imelda GI Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden (P.B.) - both in Belgium; the Department of Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel (S.S.), the Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (R.A.), and the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin (B.S.) - all in Germany; the Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (J.O.L.), the Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust (P.M.I.), and the School of Immunology and Microbial Sciences, King's College London (P.M.I.) - all in London; the Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Q.C.); and AbbVie, North Chicago, IL (E.N., K.W., T.A., K.K., W.R.D., V.P., X.H., S.B., L.S.)
| | - W Rachel Duan
- From the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal (L.P.-B.), and the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB (R.P.) - both in Canada; the Crohn's and Colitis Center at the Baton Rouge General and the GI Alliance, Baton Rouge, LA (J.C.C.); the Henry D. Janowitz Division of Gastroenterology, Department of Medicine (J.-F.C.), and the Susan and Leonard Feinstein IBD Center (M.D.), Icahn School of Medicine at Mount Sinai, New York; the Department of Pathophysiology and Transplantation, Università degli Studi di Milano and the Unit of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano (F.C.), and Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele (S.D.) - both in Milan; the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven (M.F.), and the Imelda GI Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden (P.B.) - both in Belgium; the Department of Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel (S.S.), the Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (R.A.), and the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin (B.S.) - all in Germany; the Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (J.O.L.), the Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust (P.M.I.), and the School of Immunology and Microbial Sciences, King's College London (P.M.I.) - all in London; the Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Q.C.); and AbbVie, North Chicago, IL (E.N., K.W., T.A., K.K., W.R.D., V.P., X.H., S.B., L.S.)
| | - Valerie Pivorunas
- From the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal (L.P.-B.), and the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB (R.P.) - both in Canada; the Crohn's and Colitis Center at the Baton Rouge General and the GI Alliance, Baton Rouge, LA (J.C.C.); the Henry D. Janowitz Division of Gastroenterology, Department of Medicine (J.-F.C.), and the Susan and Leonard Feinstein IBD Center (M.D.), Icahn School of Medicine at Mount Sinai, New York; the Department of Pathophysiology and Transplantation, Università degli Studi di Milano and the Unit of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano (F.C.), and Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele (S.D.) - both in Milan; the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven (M.F.), and the Imelda GI Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden (P.B.) - both in Belgium; the Department of Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel (S.S.), the Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (R.A.), and the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin (B.S.) - all in Germany; the Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (J.O.L.), the Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust (P.M.I.), and the School of Immunology and Microbial Sciences, King's College London (P.M.I.) - all in London; the Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Q.C.); and AbbVie, North Chicago, IL (E.N., K.W., T.A., K.K., W.R.D., V.P., X.H., S.B., L.S.)
| | - Xiu Huang
- From the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal (L.P.-B.), and the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB (R.P.) - both in Canada; the Crohn's and Colitis Center at the Baton Rouge General and the GI Alliance, Baton Rouge, LA (J.C.C.); the Henry D. Janowitz Division of Gastroenterology, Department of Medicine (J.-F.C.), and the Susan and Leonard Feinstein IBD Center (M.D.), Icahn School of Medicine at Mount Sinai, New York; the Department of Pathophysiology and Transplantation, Università degli Studi di Milano and the Unit of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano (F.C.), and Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele (S.D.) - both in Milan; the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven (M.F.), and the Imelda GI Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden (P.B.) - both in Belgium; the Department of Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel (S.S.), the Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (R.A.), and the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin (B.S.) - all in Germany; the Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (J.O.L.), the Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust (P.M.I.), and the School of Immunology and Microbial Sciences, King's College London (P.M.I.) - all in London; the Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Q.C.); and AbbVie, North Chicago, IL (E.N., K.W., T.A., K.K., W.R.D., V.P., X.H., S.B., L.S.)
| | - Sofie Berg
- From the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal (L.P.-B.), and the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB (R.P.) - both in Canada; the Crohn's and Colitis Center at the Baton Rouge General and the GI Alliance, Baton Rouge, LA (J.C.C.); the Henry D. Janowitz Division of Gastroenterology, Department of Medicine (J.-F.C.), and the Susan and Leonard Feinstein IBD Center (M.D.), Icahn School of Medicine at Mount Sinai, New York; the Department of Pathophysiology and Transplantation, Università degli Studi di Milano and the Unit of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano (F.C.), and Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele (S.D.) - both in Milan; the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven (M.F.), and the Imelda GI Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden (P.B.) - both in Belgium; the Department of Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel (S.S.), the Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (R.A.), and the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin (B.S.) - all in Germany; the Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (J.O.L.), the Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust (P.M.I.), and the School of Immunology and Microbial Sciences, King's College London (P.M.I.) - all in London; the Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Q.C.); and AbbVie, North Chicago, IL (E.N., K.W., T.A., K.K., W.R.D., V.P., X.H., S.B., L.S.)
| | - Lei Shu
- From the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal (L.P.-B.), and the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB (R.P.) - both in Canada; the Crohn's and Colitis Center at the Baton Rouge General and the GI Alliance, Baton Rouge, LA (J.C.C.); the Henry D. Janowitz Division of Gastroenterology, Department of Medicine (J.-F.C.), and the Susan and Leonard Feinstein IBD Center (M.D.), Icahn School of Medicine at Mount Sinai, New York; the Department of Pathophysiology and Transplantation, Università degli Studi di Milano and the Unit of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano (F.C.), and Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele (S.D.) - both in Milan; the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven (M.F.), and the Imelda GI Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden (P.B.) - both in Belgium; the Department of Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel (S.S.), the Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (R.A.), and the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin (B.S.) - all in Germany; the Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (J.O.L.), the Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust (P.M.I.), and the School of Immunology and Microbial Sciences, King's College London (P.M.I.) - all in London; the Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Q.C.); and AbbVie, North Chicago, IL (E.N., K.W., T.A., K.K., W.R.D., V.P., X.H., S.B., L.S.)
| | - Marla Dubinsky
- From the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal (L.P.-B.), and the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB (R.P.) - both in Canada; the Crohn's and Colitis Center at the Baton Rouge General and the GI Alliance, Baton Rouge, LA (J.C.C.); the Henry D. Janowitz Division of Gastroenterology, Department of Medicine (J.-F.C.), and the Susan and Leonard Feinstein IBD Center (M.D.), Icahn School of Medicine at Mount Sinai, New York; the Department of Pathophysiology and Transplantation, Università degli Studi di Milano and the Unit of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano (F.C.), and Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele (S.D.) - both in Milan; the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven (M.F.), and the Imelda GI Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden (P.B.) - both in Belgium; the Department of Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel (S.S.), the Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (R.A.), and the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin (B.S.) - all in Germany; the Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (J.O.L.), the Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust (P.M.I.), and the School of Immunology and Microbial Sciences, King's College London (P.M.I.) - all in London; the Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Q.C.); and AbbVie, North Chicago, IL (E.N., K.W., T.A., K.K., W.R.D., V.P., X.H., S.B., L.S.)
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17
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Wu JF, Yen HH, Wang HY, Chang TA, Chang CH, Chang CW, Chao TH, Chou JW, Chou YH, Chuang CH, Hsu WH, Hsu TC, Huang TY, Hung TI, Le PH, Lin CC, Lin CC, Lin CP, Lin JK, Lin WC, Ni YH, Shieh MJ, Shih IL, Shun CT, Tsai TJ, Wang CY, Weng MT, Wong JM, Wu DC, Wei SC. Management of Crohn's disease in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease updated in 2023. Intest Res 2024; 22:250-285. [PMID: 39099218 PMCID: PMC11309825 DOI: 10.5217/ir.2024.00060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 06/06/2024] [Accepted: 06/13/2024] [Indexed: 08/06/2024] Open
Abstract
Crohn's disease (CD) is a chronic, fluctuating inflammatory condition that primarily affects the gastrointestinal tract. Although the incidence of CD in Taiwan is lower than that in Western countries, the severity of CD presentation appears to be similar between Asia and the West. This observation indicates the urgency for devising revised guidelines tailored to the unique reimbursement system, and patient requirements in Taiwan. The core objectives of these updated guidelines include the updated treatment choices and the integration of the treat-to-target strategy into CD management, promoting the achievement of deep remission to mitigate complications and enhance the overall quality of life. Given the diversity in disease prevalence, severity, insurance policies, and access to medical treatments in Taiwan, a customized approach is imperative for formulating these guidelines. Such tailored strategies ensure that international standards are not only adapted but also optimized to local contexts. Since the inception of its initial guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease (TSIBD) has acknowledged the importance of continuous revisions for incorporating new therapeutic options and evolving disease management practices. The latest update leverages international standards and recent research findings focused on practical implementation within the Taiwanese healthcare system.
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Affiliation(s)
- Jia-Feng Wu
- Department of Pediatrics, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Hsu-Heng Yen
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan
- Department of Post-Baccalaureate Medicine, National Chung Hsing University College of Medicine, Taichung, Taiwan
| | - Horng-Yuan Wang
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
- MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan
- MacKay Medical College, Taipei, Taiwan
| | - Ting-An Chang
- Department of Pathology, Taipei City Hospital, Renai-Branch, Taipei, Taiwan
| | - Chung-Hsin Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Chen-Wang Chang
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
- MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan
- MacKay Medical College, Taipei, Taiwan
| | - Te-Hsin Chao
- Division of Colon and Rectal Surgery, Department of Surgery, Chiayi and Wangiao Branch, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Jen-Wei Chou
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Chinese Medicine, China Medical University, Taichung, Taiwan
| | - Yenn-Hwei Chou
- Division of General Surgery, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
| | - Chiao-Hsiung Chuang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Wen-Hung Hsu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan
| | - Tzu-Chi Hsu
- Division of Colon and Rectal Surgery, Department of Surgery, MacKay Memorial Hospital, MacKay Medical College, Taipei, Taiwan
| | - Tien-Yu Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Tsung-I Hung
- Division of General Surgery, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
| | - Puo-Hsien Le
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
- Chang Gung Microbiota Therapy Center, Linkou Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
- Inflammatory Bowel Disease Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
| | - Chun-Che Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taipei, Taiwan
| | - Chun-Chi Lin
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Surgery, Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ching-Pin Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taipei, Taiwan
| | - Jen-Kou Lin
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Surgery, Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Wei-Chen Lin
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
| | - Yen-Hsuan Ni
- Department of Pediatrics, National Taiwan University Children’s Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ming-Jium Shieh
- Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - I-Lun Shih
- Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Tung Shun
- Department of Forensic Medicine and Pathology, National Taiwan University Hospital, Taipei, Taiwan
- Department of Pathology, Good Liver Clinic, Taipei, Taiwan
| | - Tzung-Jiun Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Cheng-Yi Wang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Meng-Tzu Weng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan
| | - Jau-Min Wong
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Deng-Chyang Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Gangshan Hospital, Kaohsiung, Taiwan
- Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shu-Chen Wei
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
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Ylisaukko-oja T, af Björkesten CG, Eberl A, Nuutinen H, Jussila A, Molander P, Koskela R, Blomster T, Pajala M, Ilus T, Haiko P, Kovac B, Silvola S, Smith S, Jokelainen J, Sipponen T. Real-life treatment persistence and treatment outcomes of Finnish patients with inflammatory bowel disease receiving vedolizumab as first-line biological treatment. Heliyon 2024; 10:e32432. [PMID: 38975101 PMCID: PMC11225725 DOI: 10.1016/j.heliyon.2024.e32432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 06/03/2024] [Accepted: 06/04/2024] [Indexed: 07/09/2024] Open
Abstract
Purpose To analyze treatment persistence and treatment outcomes of vedolizumab as first-line biological treatment in Crohn's disease (CD) and ulcerative colitis (UC) patients in a Finnish real-world setting. Methods Observational, retrospective, multi-center chart review study that included adult CD and UC patients initiating vedolizumab as first-line biological treatment between 2014 and 2020. Results The cohort consisted of 54 CD and 69 UC patients. At month 12, treatment persistence was 84.9 % in CD and 64.7 % in UC. Most vedolizumab discontinuations (CD, n = 11; UC, n = 26) were due to inefficacy. Discontinuations due to adverse events were rare (n < 5). Efficacy improvements were observed in treatment persistent patients at 12 months vs. baseline in the Harvey-Bradshaw Index (CD, 1.8 vs. 3.9, p = 0.001), Partial Mayo Score (UC, 1.0 vs. 4.9, p < 0.001), Physician's Global Assessment (CD, 0.9 vs. 1.8, p < 0.001; UC, 0.4 vs. 2.1, p < 0.001), along with positive endoscopic and biochemical outcomes. Clinical remission was 90.9 % vs. 63.0 % for CD, and 81.6 % vs. 12.3 % for UC, while corticosteroid use was 15.9 % vs. 53.7 % for CD, and 14.6 % vs. 92.8 % for UC at 12 months and baseline, respectively. Conclusion Vedolizumab was associated with improvements in efficacy, endoscopic activity, biochemical parameters, and decreased corticosteroid burden when used as a first-line biological treatment.
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Affiliation(s)
| | - Clas-Göran af Björkesten
- Abdominal Center, Gastroenterology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Anja Eberl
- Abdominal Center, Gastroenterology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Heikki Nuutinen
- Division of Gastroenterology, Department of Medicine, Turku University Hospital, Turku, Finland
| | - Airi Jussila
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland
| | - Pauliina Molander
- Abdominal Center, Gastroenterology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Ritva Koskela
- Department of Medicine, Division of Gastroenterology, Oulu University Hospital, Oulu, Finland
| | - Timo Blomster
- Department of Medicine, Division of Gastroenterology, Oulu University Hospital, Oulu, Finland
| | - Markku Pajala
- Department of Internal Medicine, Kuopio University Hospital, Kuopio, Finland
| | - Tuire Ilus
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland
| | | | | | | | | | | | - Taina Sipponen
- Abdominal Center, Gastroenterology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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Alkhaldi W, Elsharkawy MS, Bashaib AH, Alsakkaf H, Alali MA, Alfheed BR, Alahaideb BA, Alharbi MM, Alzahrani SM. Comparative Assessment of Crohn's Disease Activity Using Magnetic Resonance Enterography and Endoscopy. Cureus 2024; 16:e61247. [PMID: 38939292 PMCID: PMC11210573 DOI: 10.7759/cureus.61247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Accepted: 05/17/2024] [Indexed: 06/29/2024] Open
Abstract
Introduction Magnetic resonance enterography (MRE) has emerged as a promising technique for evaluating the extent and severity of Crohn's disease activity. To compare how we measure Crohn's disease activity with MRE and endoscopy. Material and methods We retrospectively reviewed MRE studies of 60 patients with suspicious Crohn's disease who underwent 1.5-T MRI examinations (T1-weighted images pre- and post-IV contrast medium administration and T2-weighted images) and endoscopy within one month, and they were evaluated by one radiology consultant with experience of 17 years. Endoscopy was used as the reference standard for diagnosing active Crohn's disease cases. Data analysis was performed using the websites (www.graphpad.com and www.medcalc.org) and Microsoft Excel (Microsoft® Corp., Redmond, USA). Results A total of 35 patients were included in the study. The remaining 25 patients were excluded either due to non-available data in the endoscopy report or cases of non-Crohn's disease. The MRI examinations were reviewed by one radiology consultant and revealed 27 active and eight non-active Crohn's disease cases compared to 30 active and five non-active Crohn's disease cases in endoscopy. The sensitivity of MRI in detecting active cases of Crohn's disease compared to endoscopy was 83.3% and the specificity of 60%. The strength of agreement between both methods was fair to good (Kappa = 0.347, p-value = 0.4497, Chi-squared = 0.571 with one degree of freedom). Conclusion MRE statistically has a good impact on the assessment of Crohn's disease as well as endoscopy with the parameters used in this study. Non-invasiveness and the changes of activity seen in the bowel proximal to the ileocecal junction undetectable by endoscopy make MRE more practically applicable in this aspect.
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Affiliation(s)
| | | | - Ali H Bashaib
- Gastroenterology and Hepatology, Prince Mohammad Bin Abdulaziz Hospital, Riyadh, SAU
| | - Hussein Alsakkaf
- Radiology and Medical Imaging, King Saud University Medical City, Riyadh, SAU
| | | | | | | | | | - Saud M Alzahrani
- General Physician, Prince Meshari Bin Saud General Baljarshi Hospital, Al Bahah, SAU
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Lee YJ, Kwak SG, Kim ES, Kim SK, Lee HS, Chung YJ, Jang BI, Kim KO, Kim J, Jo HH, Kim EY. Mobile monitoring system detects the disease activity pattern and shows the association with clinical outcomes in patients with newly diagnosed Crohn's disease. Sci Rep 2024; 14:9405. [PMID: 38658648 PMCID: PMC11043071 DOI: 10.1038/s41598-024-59914-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Accepted: 04/16/2024] [Indexed: 04/26/2024] Open
Abstract
We aimed to determine whether Crohn's disease (CD) activity patterns assessed via a web-based symptom diary can help predict clinical outcomes in patients with newly diagnosed CD. Patients diagnosed with CD within the preceding 3 months were prospectively enrolled at four tertiary centers. All patients recorded their symptoms on a website using a smartphone at least once a week. The index outcomes were disease-related admission and surgery during follow-up. The disease activity from enrollment to outcome or last follow-up was reviewed for pattern analysis. Cox regression analysis was used to identify the predictors of disease outcomes. A total of 102 patients were enrolled. During a median follow-up period of 42 months, 25 (24.5%) and 6 (5.9%) patients required admission and surgery, respectively. Poor activity pattern was an independent predictor of disease-related hospitalization (adjusted hazard ratio [aHR], 3.96; 95% confidence interval [CI] 1.5-10.45; p = 0.005). A poor activity pattern (aHR, 19.48; 95% CI 1.86-203.95; p = 0.013) and female sex (aHR, 11.28; 95% CI 1.49-85.01; p = 0.018) were found to be independent predictors of bowel resection. CD disease activity patterns monitored through the mobile monitoring system may help predict clinical outcomes, such as disease-related hospitalization and surgery, in patients with newly diagnosed CD.
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Affiliation(s)
- Yoo Jin Lee
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea
| | - Sang Gyu Kwak
- Department of Medical Statistics, Catholic University of Daegu School of Medicine, Daegu, South Korea
| | - Eun Soo Kim
- Department of Internal Medicine, School of Medicine, Kyungpook National University, 130 Dongdeuk-ro, Jung-gu, Daegu, South Korea.
| | - Sung Kook Kim
- Department of Internal Medicine, School of Medicine, Kyungpook National University, 130 Dongdeuk-ro, Jung-gu, Daegu, South Korea
| | - Hyun Seok Lee
- Department of Internal Medicine, School of Medicine, Kyungpook National University, 130 Dongdeuk-ro, Jung-gu, Daegu, South Korea
| | - Yun Jin Chung
- Department of Internal Medicine, School of Medicine, Kyungpook National University, 130 Dongdeuk-ro, Jung-gu, Daegu, South Korea
| | - Byung Ik Jang
- Department of Internal Medicine, Yeungnam University College of Medicine, 317‑1 Daemyung 5 Dong, Daegu, 705-703, South Korea.
| | - Kyeong Ok Kim
- Department of Internal Medicine, Yeungnam University College of Medicine, 317‑1 Daemyung 5 Dong, Daegu, 705-703, South Korea
| | - Jeongseok Kim
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea
| | - Hyeong Ho Jo
- Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, South Korea
| | - Eun Young Kim
- Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, South Korea
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Leoncini G, Reggiani-Bonetti L, Simoncelli G, Villanacci V. Histology of IBD and related colitides in the elderly. Minerva Gastroenterol (Torino) 2024; 70:68-78. [PMID: 34278750 DOI: 10.23736/s2724-5985.21.02888-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Inflammatory bowel disease (IBD) are chronic relapsing diseases, affecting both children and adults with a life-long duration. An increased co-morbidity gives raise to fragility in the elderly. In this regard it should consider that several non-IBD colitides may mimic both ulcerative colitis and Crohn's disease. Moreover, chronic diseases represent a clinical challenge, mostly about treatment effectiveness. Finally, it is worth noting that patients with long-standing diseases - and elderly patients among them - have an increased malignancy risk when compared to general (non-IBD) population. Our paper aims to review the three main histological topics that play a role in the clinical management of IBD in the elderly, namely differential diagnosis, mucosal healing and IBD-associated dysplasia.
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Affiliation(s)
- Giuseppe Leoncini
- Unit of Pathology, ASST del Garda, Desenzano del Garda, Brescia, Italy -
| | - Luca Reggiani-Bonetti
- Unit of Pathology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy
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22
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Bak MT, ten Bokkel Huinink S, Erler NS, Bodelier AG, Dijkstra G, Romberg-Camps M, de Boer NK, Hoentjen F, Stassen LP, van der Meulen–de Jong AE, West RL, van Ruler O, van der Woude CJ, de Vries AC. Prognostic Value of the Modified Rutgeerts Score for Long-Term Outcomes After Primary Ileocecal Resection in Crohn's Disease. Am J Gastroenterol 2024; 119:306-312. [PMID: 37737675 PMCID: PMC10833187 DOI: 10.14309/ajg.0000000000002509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Accepted: 08/29/2023] [Indexed: 09/23/2023]
Abstract
INTRODUCTION The prognostic value of the modified Rutgeerts score (mRS) in patients with Crohn's disease (CD) needs to be further elucidated. This study assessed the prognostic value of the mRS for long-term outcomes after primary ileocecal resection in patients with CD. METHODS Patients with CD after primary ileocecal resection with an available mRS at first postoperative ileocolonoscopy (index mRS) were retrospectively included. The primary outcome was surgical recurrence. Secondary outcomes were clinical recurrence and progression to severe endoscopic recurrence (≥i3). Cox proportional hazard models were used to assess the association between index mRS and outcomes. RESULTS Six hundred fifty-two patients were included (mean follow-up: 6.4 years, SD: 4.6). Surgical recurrence rates were 7.7%, 5.3%, 12.9%, 19.1%, 28.8%, 47.8% for index mRS i0, i1, i2a, i2b, i3, and i4, respectively. Clinical recurrence occurred in 42.2% (i0), 53.7% (i1), 58.5% (i2a), 80.2% (i2b), 79.4% (i3), and 95.3% (i4) of patients. Progression to severe endoscopic recurrence occurred in 21.1% (i0), 33.9% (i1), 26.8% (i2a), and 33.3% (i2b) of patients. An index mRS of i2b (adjusted hazard ratio [aHR] 3.0; 1.5-5.6), i3 (aHR 4.0; 2.0-7.9) and i4 (aHR 8.0; 4.0-16.0) were associated with surgical recurrence. An index mRS of i1 (aHR 1.7; 1.2-2.4), i2a (aHR 1.7; 1.2-2.4), i2b (aHR 4.4; 3.2-6.0), i3 (aHR 3.6; 2.5-5.2), and i4 (aHR 7.3; 4.8-10.9) were associated with clinical recurrence. An index mRS of i1 (aHR 2.0; 1.1-3.7) or i2b (aHR 2.5; 1.4-4.6) was associated with progression to severe endoscopic recurrence. DISCUSSION The increasing mRS corresponds closely with the risk of surgical and clinical recurrence. An index mRS ≥ i2b is associated with surgical recurrence, an index mRS ≥ i1 is associated with clinical recurrence, and i1 or i2b with progression to severe endoscopic recurrence. These results support tight monitoring of disease activity and treatment optimization in patients with ileal lesions and a more conservative management in patients with anastomotic lesions.
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Affiliation(s)
- Michiel T.J. Bak
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Sebastiaan ten Bokkel Huinink
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Nicole S. Erler
- Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
- Department of Biostatistics, Erasmus MC University Medical Center, Rotterdam, the Netherlands
| | | | - Gerard Dijkstra
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, the Netherlands
| | - Mariëlle Romberg-Camps
- Department of Gastroenterology, Geriatrics, Internal and Intensive Care Medicine (Co-MIK), Zuyderland Medical Centre, Heerlen-Sittard-Geleen, the Netherlands
| | - Nanne K.H. de Boer
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Amsterdam, the Netherlands
| | - Frank Hoentjen
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands
- Division of Gastroenterology, University of Alberta, Edmonton, Canada;
| | - Laurents P.S. Stassen
- Department of Surgery, Maastricht University Medical Center, Maastricht, the Netherlands
| | | | - Rachel L. West
- Department of Gastroenterology and Hepatology, Franciscus Gasthuis & Vlietland, Rotterdam, the Netherlands
| | - Oddeke van Ruler
- Department of Surgery, IJsselland Ziekenhuis, Cappelle aan den IJssel, the Netherlands
- Department of Surgery, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - C. Janneke van der Woude
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Annemarie C. de Vries
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands
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23
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Wang C, Ishizuka T, Tanaka M, Matsuo K, Knight H, Harvey N, Gillespie-Akar L, Gibble TH. Bowel Urgency in Patients with Ulcerative Colitis and Crohn's Disease: A Cross-Sectional Real-World Survey in Japan. Adv Ther 2024; 41:431-450. [PMID: 37999831 PMCID: PMC10796472 DOI: 10.1007/s12325-023-02726-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 10/31/2023] [Indexed: 11/25/2023]
Abstract
INTRODUCTION Bowel urgency (BU) is among the most disruptive of inflammatory bowel disease (IBD) symptoms. However, data on its prevalence and association with disease activity are limited. This real-world study of Japanese patients with IBD evaluated BU prevalence and compared clinical outcomes and health-related quality of life (HRQoL) between patients with and without BU. METHODS Data were drawn from the Adelphi IBD Disease Specific Programme™, a cross-sectional survey of physicians and their patients with ulcerative colitis (UC) and Crohn's disease (CD). Physicians reported demographic and clinical data, including disease activity measures (Mayo score and CD Activity Index [CDAI]), for consulting patients, who voluntarily completed a patient-reported questionnaire, including HRQoL measures (Short IBD Questionnaire [SIBDQ] and EQ-5D-5L). Outcomes were compared between patients with and without BU using t-, Fisher exact and Mann-Whitney U tests as appropriate. RESULTS Of 120 UC patients, 27.5% (n = 33) self-reported BU; physicians were unaware of BU in 54.5% (n = 18) of these patients. Patients with BU had higher mean Mayo scores (p < 0.01) and lower mean SIBDQ scores (47.9 vs 56.6, p < 0.01) than patients without BU, with mean EQ-5D-5L scores 0.83 and 0.87, respectively (p = 0.06). Physicians were satisfied with treatment but believed better control could be achieved for 39.4% of patients with BU and 35.6% without. Of 114 CD patients, 17.5% (n = 20) self-reported BU; physicians were unaware of BU in 75.0% (n = 15) of these patients. Patients with BU had higher mean CDAI scores (p < 0.01) and lower mean SIBDQ (48.7 vs 56.2, p < 0.01) and EQ-5D-5L scores (0.81 vs 0.88, p < 0.01) than patients without BU. Physicians were satisfied but believed better control could be achieved for 40.0% of patients with BU vs 19.1% without. CONCLUSIONS Patients with BU have worse clinical outcomes and HRQoL than patients without, underlining the need for improved physician-patient communication regarding BU and new IBD therapeutic options.
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Balestrieri P, Ribolsi M, Cimini P, Alvaro G, Zobel BB, Tullio A, Cicala M. Wall Thickness Ratio-A New Magnetic Resonance Parameter-Is Associated With the Outcome of Biological Therapy in Patients With Ileal and Ileocolonic Crohn's Disease. J Clin Gastroenterol 2024; 58:64-70. [PMID: 36730458 DOI: 10.1097/mcg.0000000000001809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Accepted: 10/20/2022] [Indexed: 02/04/2023]
Abstract
GOALS The present study was aimed at identifying a new magnetic resonance enterography (MRE) parameter assessing the clinical outcome of biological therapy in patients with active ileal/ileocolonic Crohn's disease (CD). BACKGROUND Transmural healing (TH) has been associated with improved outcomes in CD. However, some patients with clinical remission and inactive disease at endoscopy do not achieve TH. MATERIALS AND METHODS Ileal/ileocolonic CD patients scheduled for biological therapy were prospectively evaluated, at baseline (T0) and after 1 year of treatment (T1), with Harvey Bradshaw Index score, blood tests, ileocolonscopy, and MRE. Clinical activity was assessed after 2 years of treatment (T2). Wall thickness ratio (WTR) was calculated in the same affected ileal segment, as the ratio between the ileum wall thickness value at T1 and the ileum wall thickness value at T0. RESULTS A total of 103 patients were included. Mean WTR at T1 in nonresponders was significantly higher than in responders. At receiver operating characteristic analysis, WTR values were significantly associated to biological therapy responsiveness. A WTR cutoff value of 0.77 mm was identified to discriminate responders from nonresponders (sensitivity: 79%; specificity: 67%). In responders, the proportion of patients with a WTR<0.77 was significantly higher than the proportion of patients achieving TH at T1. Among patients achieving endoscopic remission, 11/29 (37.9%) presented TH, while 20/29 (68.9%) presented WTR<0.77 ( P : 0.035). At multivariate logistic regression analysis, WTR<0.77 was significantly associated to biological therapy response. CONCLUSION WTR index represents an easy-to-calculate MRE parameter and seems to be a promising tool for monitoring therapeutic response in CD patients during biological therapy.
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Affiliation(s)
| | | | - Paola Cimini
- Diagnostic Imaging, Campus Bio Medico University of Rome, Roma, Italy
| | - Giuseppe Alvaro
- Diagnostic Imaging, Campus Bio Medico University of Rome, Roma, Italy
| | - Bruno B Zobel
- Diagnostic Imaging, Campus Bio Medico University of Rome, Roma, Italy
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25
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Pu D, Yao Y, Zhou C, Liu R, Wang Z, Liu Y, Wang D, Wang B, Wang Y, Liu Z, Zhang Z, Feng B. FMT rescues mice from DSS-induced colitis in a STING-dependent manner. Gut Microbes 2024; 16:2397879. [PMID: 39324491 PMCID: PMC11441074 DOI: 10.1080/19490976.2024.2397879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 07/28/2024] [Accepted: 08/23/2024] [Indexed: 09/27/2024] Open
Abstract
Fecal microbiota transplantation (FMT) is currently a promising therapy for inflammatory bowel disease (IBD). However, clinical studies have shown that there is an obvious individual difference in the efficacy of FMT. Therefore, it is a pressing issue to identify the factors that influence the efficacy of FMT and find ways to screen the most suitable patients for this therapy. In this work, we targeted the stimulator of interferon genes (STING), a DNA-sensing protein that regulates host-defense. By comparing the differential efficacy of FMT in mice with different expression level of STING, it is revealed that FMT therapy provides treatment for DSS-induced colitis in a STING-dependent manner. Mechanistically, FMT exerts a regulatory effect on the differentiation of intestinal Th17 cells and macrophages, splenic Th1 and Th2 cells, as well as Th1 cells of the mesenteric lymph nodes via STING, down-regulating the colonic M1/M2 and splenic Th1/Th2 cell ratios, thereby improving the imbalanced immune homeostasis in the inflamed intestine. Meanwhile, based on the 16SrDNA sequencing of mice fecal samples, STING was found to facilitate the donor strain colonization in recipients' gut, mainly Lactobacillales, thereby reshaping the gut microbiota disturbed by colitis. Consequently, we proposed that STING, as a key target of FMT therapy, is potentially a biomarker for screening the most suitable individuals for FMT to optimize treatment regimens and enhance clinical benefit.
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Affiliation(s)
- Dan Pu
- Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yao Yao
- Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Chuan Zhou
- Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Ruixian Liu
- Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhihong Wang
- Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yan Liu
- Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Dandan Wang
- Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Binbin Wang
- Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yaohe Wang
- National Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
- Centre for Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, UK
| | - Zhanju Liu
- Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Gastroenterology, the Shanghai Tenth People's Hospital of Tongji University, Shanghai, China
| | - Zhe Zhang
- Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Baisui Feng
- Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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26
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Herrlinger KR, Stange EF. To STRIDE or not to STRIDE: a critique of "treat to target" in Crohn´s disease. Expert Rev Gastroenterol Hepatol 2023; 17:1205-1219. [PMID: 38131269 DOI: 10.1080/17474124.2023.2296564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Accepted: 12/14/2023] [Indexed: 12/23/2023]
Abstract
INTRODUCTION The STRIDE consensus suggested to focus on mucosal healing, based on biomarkers and endoscopy, in addition to clinical endpoints as treatment target. This narrative review provides a critique of this concept in Crohn´s disease. AREAS COVERED We analyze and discuss the limitations of endpoints as targets, their currently limited achievability, and the controversial evidence relating to 'treat to target.' The relevant publications in Pubmed were identified in a literature review with the key word 'Crohn´s disease.' EXPERT OPINION All targets and endpoints have their limitations, and, even if reached, not all have unequivocally been shown to improve prognosis. The major deficiency of STRIDE is not only the lack of validation and agreement upon endpoints but little evidence of their achievability in a sizable proportion of patients by dose or timing adjustments or switching the medication. Above all, the concept should be based on clear evidence that patients indeed benefit from appropriate escalation of treatment and relevant controlled studies in this regard have been controversial. Until the STRIDE approach is proven to be superior to standard treatment focusing on clinical well-being, the field should remain reluctant and expect more convincing evidence before new targets are approved.
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Affiliation(s)
| | - Eduard F Stange
- Innere Medizin I, UniversitätsklinikTübingen, Tübingen, Germany
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27
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Al-jabri R, Wetwittayakhlang P, Lakatos PL. Monitoring of Inflammatory Bowel Disease in Pregnancy: A Review of the Different Modalities. J Clin Med 2023; 12:7343. [PMID: 38068395 PMCID: PMC10707304 DOI: 10.3390/jcm12237343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 11/23/2023] [Accepted: 11/23/2023] [Indexed: 09/14/2024] Open
Abstract
Inflammatory Bowel Disease (IBD) significantly affects women in their reproductive years. Understanding the relationship between IBD and pregnancy is crucial, given its impact across pre-gestational, gestational, and postpartum phases. Monitoring IBD activity during pregnancy involves various modalities. This review discusses these modalities, focusing on the efficacy and safety of Small Intestine Ultrasound (IUS) as a noninvasive and reliable option. While IUS has gained popularity, its technique-sensitive nature necessitates trained staff for optimal usage.
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Affiliation(s)
- Reem Al-jabri
- Division of Gastroenterology and Hepatology, McGill University Health Center, Montreal, QC H3G 1Y6, Canada;
| | - Panu Wetwittayakhlang
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand
| | - Peter L. Lakatos
- Division of Gastroenterology and Hepatology, McGill University Health Center, Montreal, QC H3G 1Y6, Canada;
- Department of Oncology and Medicine, Semmelweis University, 1085 Budapest, Hungary
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28
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Sabino J, Tarassishin L, Eisele C, Hawkins K, Barré A, Nair N, Rendon A, Debebe A, Picker M, Agrawal M, Stone J, George J, Legnani P, Maser E, Chen CL, Thjømøe A, Mørk E, Dubinsky M, Hu J, Colombel JF, Peter I, Torres J. Influence of Early Life Factors, including breast milk Composition, on the Microbiome of Infants Born to Mothers with and without Inflammatory Bowel Disease. J Crohns Colitis 2023; 17:1723-1732. [PMID: 37279927 PMCID: PMC10673817 DOI: 10.1093/ecco-jcc/jjad096] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 03/29/2023] [Accepted: 06/05/2023] [Indexed: 06/08/2023]
Abstract
BACKGROUND AND AIMS Herein we analysed the influence of early life factors, including breast milk composition, on the development of the intestinal microbiota of infants born to mothers with and without IBD. METHODS The MECONIUM [Exploring MEChanisms Of disease traNsmission In Utero through the Microbiome] study is a prospective cohort study consisting of pregnant women with or without IBD and their infants. Longitudinal stool samples were collected from babies and analysed using 16s rRNA sequencing and faecal calprotectin. Breast milk proteomics was profiled using Olink inflammation panel. RESULTS We analysed gut microbiota of 1034 faecal samples from 294 infants [80 born to mothers with and 214 to mothers without IBD]. Alpha diversity was driven by maternal IBD status and time point. The major influencers of the overall composition of the microbiota were mode of delivery, feeding, and maternal IBD status. Specific taxa were associated with these exposures, and maternal IBD was associated with a reduction in Bifidobacterium. In 312 breast milk samples [91 from mothers with IBD], mothers with IBD displayed lower abundance of proteins involved in immune regulation, such as thymic stromal lymphopoietin, interleukin-12 subunit beta, tumour necrosis factor-beta, and C-C motif chemokine 20, as compared with control mothers [adjusted p = 0.0016, 0.049, 0.049, and 0.049, respectively], with negative correlations with baby´s calprotectin, and microbiome at different time points. CONCLUSION Maternal IBD diagnosis influences microbiota in their offspring during early life. The proteomic profile of breast milk of women with IBD differs from that of women without IBD, with distinct time-dependent associations with baby's gut microbiome and feacal calprotectin.
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Affiliation(s)
- João Sabino
- Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences, New York, NY, USA
- Icahn School of Medicine at Mount Sinai, Division of Gastroenterology, Department of Medicine, New York, NY, USA
- Department of Gastroenterology, University Hospitals of Leuven, Leuven, Belgium
| | - Leonid Tarassishin
- Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences, New York, NY, USA
| | - Caroline Eisele
- Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences, New York, NY, USA
- College of Medicine, Pennsylvania State University College of Medicine, Hershey, PA, USA
| | - Kelly Hawkins
- Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences, New York, NY, USA
| | - Amelie Barré
- Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences, New York, NY, USA
| | - Nile Nair
- Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences, New York, NY, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Alexa Rendon
- Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences, New York, NY, USA
| | - Anketse Debebe
- Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences, New York, NY, USA
| | - Mellissa Picker
- Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences, New York, NY, USA
| | - Manasi Agrawal
- Icahn School of Medicine at Mount Sinai, Division of Gastroenterology, Department of Medicine, New York, NY, USA
- Center for Molecular Prediction of IBD [PREDICT], Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Joanne Stone
- Gastroenterology Division, Icahn School of Medicine at Mount Sinai, Department of Obstetrics, Gynecology and Reproductive Sciences, New York, NY, USA
| | - James George
- Icahn School of Medicine at Mount Sinai, Division of Gastroenterology, Department of Medicine, New York, NY, USA
| | - Peter Legnani
- Icahn School of Medicine at Mount Sinai, Division of Gastroenterology, Department of Medicine, New York, NY, USA
| | - Elana Maser
- Icahn School of Medicine at Mount Sinai, Division of Gastroenterology, Department of Medicine, New York, NY, USA
| | - Ching-Lynn Chen
- Gastroenterology Division, Icahn School of Medicine at Mount Sinai, Department of Obstetrics, Gynecology and Reproductive Sciences, New York, NY, USA
| | | | | | - Marla Dubinsky
- Icahn School of Medicine at Mount Sinai, Division of Pediatric Gastroenterology and Hepatology, New York, NY, USA
| | - Jianzhong Hu
- Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences, New York, NY, USA
| | - Jean-Frederic Colombel
- Icahn School of Medicine at Mount Sinai, Division of Gastroenterology, Department of Medicine, New York, NY, USA
| | - Inga Peter
- Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences, New York, NY, USA
| | - Joanna Torres
- Icahn School of Medicine at Mount Sinai, Division of Gastroenterology, Department of Medicine, New York, NY, USA
- Gastroenterology Division, Hospital Beatriz Ângelo, Loures, Portugal
- Gastroenterology Division, Hospital da Luz, Lisbon, Portugal
- Faculdade de Medicina, Universidade de Lisboa, Portugal
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29
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Evaristo G, Szczepanski J, Farag MS, Rubin DT, Campbell LK, Marcus VA, Lamps LW, Hart J. Crohn's Disease Features in Anastomotic Biopsies from Patients With and Without Crohn's Disease: Diagnostic and Prognostic Value. Mod Pathol 2023; 36:100325. [PMID: 37660927 DOI: 10.1016/j.modpat.2023.100325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Revised: 08/14/2023] [Accepted: 08/29/2023] [Indexed: 09/05/2023]
Abstract
Endoscopic evidence of disease activity is a critical predictor of clinical relapse in patients with Crohn's disease (CD), and histologic disease activity is evolving as a similarly important end point for patient management. However, classical morphologic features of CD may overlap with postoperative inflammatory changes, confounding the evaluation of anastomotic biopsies. There is a clear unmet need for better characterization of diagnostic and clinically significant histologic features of CD in these surgically altered sites. We evaluated ileocolonic and colocolonic/rectal anastomotic biopsies performed at 3 academic institutions in patients with and without CD. The biopsies were blindly assessed for CD histologic features and correlated to clinical and endoscopic characteristics. In CD patients, the presence of each feature was correlated with the subsequent clinical exacerbation or relapse. We obtained anastomotic biopsies from 208 patients, of which 109 were operated on for CD and 99 for another indication (neoplasia [80%], diverticular disease (11%), and other [9%]). Mean time since surgery was 10 years (0-59; 14 years for CD [1-59], 6 years for non-CD [0-33]). Endoscopic inflammation was noted in 52% of cases (68% for CD and 35% for non-CD). Microscopic inflammation was present in 74% of cases (82% for CD and 67% for non-CD). Only discontinuous lymphoplasmacytosis (P < .001) and pyloric gland metaplasia (P = .04) occurred significantly more often in CD patients. However, none of the histologic features predicted clinical disease progression. In subset analysis, the presence of histologic features of CD in nonanastomotic biopsies obtained concurrently in CD patients was significantly associated with relapse (P = .03). Due to extensive morphologic overlap between CD and postoperative changes and the lack of specific histologic features of relapse, biopsies from anastomotic sites are of no value in predicting clinical CD progression. Instead, CD activity in biopsies obtained away from anastomotic sites should be used for guiding endoscopic sampling and clinical management.
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Affiliation(s)
| | | | - Mina S Farag
- Department of Pathology, McGill University, Montreal, Quebec, Canada
| | - David T Rubin
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, Ilinois
| | | | - Victoria A Marcus
- Department of Pathology, McGill University, Montreal, Quebec, Canada
| | - Laura W Lamps
- Department of Pathology, University of Michigan, Ann Arbor, Michigan
| | - John Hart
- Department of Pathology, University of Chicago, Chicago, Illinois.
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30
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Kumar P, Vuyyuru SK, Das P, Kante B, Ranjan MK, Thomas DM, Mundhra S, Sahu P, Venigalla PM, Jain S, Goyal S, Golla R, Virmani S, Singh MK, Sachdeva K, Sharma R, Dash NR, Makharia G, Kedia S, Ahuja V. Serum albumin is the strongest predictor of anti-tumor necrosis factor nonresponse in inflammatory bowel disease in resource-constrained regions lacking therapeutic drug monitoring. Intest Res 2023; 21:460-470. [PMID: 36926698 PMCID: PMC10626021 DOI: 10.5217/ir.2022.00128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 01/03/2023] [Accepted: 01/09/2023] [Indexed: 03/18/2023] Open
Abstract
BACKGROUND/AIMS Evidence on predictors of primary nonresponse (PNR), and secondary loss of response (SLR) to anti-tumor necrosis factor (anti-TNF) agents in inflammatory bowel disease is scarce from Asia. We evaluated clinical/biochemical/molecular markers of PNR/SLR in ulcerative colitis (UC) and Crohn's disease (CD). METHODS Inflammatory bowel disease patients treated with anti-TNF agents (January 2005-October 2020) were ambispectively included. Data concerning clinical and biochemical predictors was retrieved from a prospectively maintained database. Immunohistochemistry for expression of oncostatin M (OSM), OSM receptor (OSM-R), and interleukin-7 receptor (IL-7R) were done on pre anti-TNF initiation mucosal biopsies. RESULTS One-hundred eighty-six patients (118 CD, 68 UC: mean age, 34.1±13.7 years; median disease duration at anti-TNF initiation, 60 months; interquartile range, 28-100.5 months) were included. PNR was seen in 17% and 26.5% and SLR in 47% and 28% CD and UC patients, respectively. In CD, predictors of PNR were low albumin (P<0.001), postoperative recurrence (P=0.001) and high IL-7R expression (P<0.027) on univariate; and low albumin alone (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.03-0.28; P<0.001) on multivariate analysis respectively. Low albumin (HR, 0.31; 95% CI, 0.15-0.62; P=0.001) also predicted SLR. In UC, predictors of PNR were low albumin (P<0.001), and high C-reactive protein (P<0.001), OSM (P<0.04) and OSM-R (P=0.07) stromal expression on univariate; and low albumin alone (HR, 0.11; 95% CI, 0.03-0.39; P=0.001) on multivariate analysis respectively. CONCLUSIONS Low serum albumin at baseline significantly predicted PNR in UC and PNR/SLR in CD patients. Mucosal markers of PNR were high stromal OSM/OSM-R in UC and high IL-7R in CD patients.
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Affiliation(s)
- Peeyush Kumar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Sudheer K. Vuyyuru
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Prasenjit Das
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Bhaskar Kante
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Mukesh Kumar Ranjan
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - David Mathew Thomas
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Sandeep Mundhra
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Pabitra Sahu
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Pratap Mouli Venigalla
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Saransh Jain
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Sandeep Goyal
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Rithvik Golla
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Shubi Virmani
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Mukesh K. Singh
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Karan Sachdeva
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Raju Sharma
- Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India
| | - Nihar Ranjan Dash
- Department of Gastrointestinal Surgery, All India Institute of Medical Sciences, New Delhi, India
| | - Govind Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Saurabh Kedia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
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Narula N, Wong ECL, Aruljothy A, Dulai PS, Colombel JF, Marshall JK, Ferrante M, Reinisch W. Baseline Patient-reported Symptoms Less Predictive Than MM-SES-CD for Endoscopic Remission in Crohn's Disease. J Clin Gastroenterol 2023; 57:913-919. [PMID: 36227009 DOI: 10.1097/mcg.0000000000001774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 09/04/2022] [Indexed: 12/10/2022]
Abstract
BACKGROUND This analysis evaluates the association between baseline patient-reported symptom (PRS) severity in Crohn's disease (CD), including abdominal pain, stool frequency, general well-being, and achievement of clinical and endoscopic outcomes. We compared baseline PRS to baseline endoscopic scores for the prediction of endoscopic remission (ER). METHODS This post hoc analysis of 2 clinical trials of infliximab in CD included 601 patients and evaluated baseline PRS variables (abdominal pain, stool frequency, and general well-being) as measured by the Crohn's disease activity index and their association with 6-month clinical remission (CR) (Crohn's Disease Activity Index<150), corticosteroid-free CR, and week 26/54 ER (absence of mucosal ulceration). Logistic regression models assessed the relationships between PRS and outcomes of interest. Receiver operating characteristic curve analyses compared the sensitivity and specificity of the different baseline PRS compared with baseline endoscopic scores for achievement of ER at weeks 26 and 54. RESULTS No difference was found comparing patients with higher baseline PRS to those with lower PRS in achieving 6-month CR, 6-month corticosteroid-free CR, or week 26/54 ER. Modified multiplier of the SES-CD (MM-SES-CD) at baseline demonstrated a significant ability to predict week 54 ER (area under the curve, 0.71; 95% CI 0.65-0.78; P =0.017). CONCLUSIONS Baseline PRS in CD is not prognostic of clinical or endoscopic response. In contrast, active endoscopic disease as measured by the MM-SES-CD, more accurately predicts endoscopic outcomes. Endoscopic scores such as the MM-SES-CD may be considered for selection criteria and as a primary outcome of interest in CD trials, with PRS as a co-primary or secondary endpoint.
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Affiliation(s)
- Neeraj Narula
- Division of Gastroenterology, Department of Medicine and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Emily C L Wong
- Division of Gastroenterology, Department of Medicine and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Achuthan Aruljothy
- Division of Gastroenterology, Department of Medicine and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Parambir S Dulai
- Division of Gastroenterology, Northwestern University, Chicago, IL
| | | | - John K Marshall
- Division of Gastroenterology, Department of Medicine and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Marc Ferrante
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - Walter Reinisch
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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Caballero-Mateos AM, Quesada-Caballero M, Cañadas-De la Fuente GA, Caballero-Vázquez A, Contreras-Chova F. IBD and Motherhood: A Journey through Conception, Pregnancy and Beyond. J Clin Med 2023; 12:6192. [PMID: 37834837 PMCID: PMC10573266 DOI: 10.3390/jcm12196192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 09/14/2023] [Accepted: 09/19/2023] [Indexed: 10/15/2023] Open
Abstract
Inflammatory Bowel Disease (IBD) presents distinct challenges during pregnancy due to its influence on maternal health and pregnancy outcomes. This literature review aims to dissect the existing scientific evidence on pregnancy in women with IBD and provide evidence-based recommendations for clinical management. A comprehensive search was conducted across scientific databases, selecting clinical studies, systematic reviews, and other pertinent resources. Numerous studies have underscored an increased risk of complications during pregnancy for women with IBD, including preterm birth, low birth weight, neonates small for gestational age, and congenital malformations. Nevertheless, it's evident that proactive disease management before and throughout pregnancy can mitigate these risks. Continuation of IBD treatment during pregnancy and breastfeeding is deemed safe with agents like thiopurines, anti-TNF, vedolizumab, or ustekinumab. However, there's a call for caution when combining treatments due to the heightened risk of severe infections in the first year of life. For small molecules, their use is advised against in both scenarios. Effective disease management, minimizing disease activity, and interdisciplinary care are pivotal in attending to women with IBD. The emphasis is placed on the continual assessment of maternal and infant outcomes and an expressed need for further research to enhance the understanding of the ties between IBD and adverse pregnancy outcomes.
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Shelygin YA, Ivashkin VT, Achkasov SI, Reshetov IV, Maev IV, Belousova EA, Vardanyan AV, Nanaeva BA, Adamyan LV, Drapkina OM, Namazova-Baranova LS, Razumovsky AY, Revishvili AS, Khatkov IE, Shabunin AV, Livzan MA, Sazhin AV, Timerbulatov VM, Khlynova OV, Abdulganieva DI, Abdulkhakov RA, Aleksandrov TL, Alekseeva OP, Alekseenko SA, Anosov IS, Bakulin IG, Barysheva OY, Bolikhov KV, Veselov VV, Golovenko OV, Gubonina IV, Dolgushina AI, Zhigalova TN, Kagramanova AV, Kashnikov VN, Knyazev OV, Kostenko NV, Likutov AA, Lomakina EY, Loranskaya ID, Mingazov AF, Moskalev AI, Nazarov IV, Nikitina NV, Odintsova AH, Omelyanovsky VV, Osipenko MF, Оshchepkov АV, Pavlenko VV, Poluektova EA, Rodoman GV, Segal AM, Sitkin SI, Skalinskaya MI, Surkov AN, Sushkov OI, Tarasova LV, Uspenskaya YB, Frolov SA, Chashkova EY, Shifrin OS, Shcherbakova OV, Shchukina OB, Shkurko TV, Makarchuk PA. Clinical guidelines. Crohn’s disease (К50), adults. KOLOPROKTOLOGIA 2023; 22:10-49. [DOI: 10.33878/2073-7556-2023-22-3-10-49] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/17/2024]
Affiliation(s)
- Yury A. Shelygin
- Ryzhikh National Medical Research Center of Coloproctology; Russian Medical Academy of Continuous Professional Education
| | | | - Sergey I. Achkasov
- Ryzhikh National Medical Research Center of Coloproctology; Russian Medical Academy of Continuous Professional Education
| | - Igor V. Reshetov
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - Igor V. Maev
- Moscow State University of Medicine and Dentistry named after A.I. Evdokimov
| | | | | | | | - Leila V. Adamyan
- Moscow State University of Medicine and Dentistry named after A.I. Evdokimov; Mational Medical Research Center of Obstetrics and Gynecology named after V.I. Kulakov
| | - Oksana M. Drapkina
- Moscow State University of Medicine and Dentistry named after A.I. Evdokimov; National Medical Research Center for Therapy and Preventive Medicine
| | - Leila S. Namazova-Baranova
- Reseach Instinute of Pediatrics and Child Health Protection of the Central Clinical Hospital of the Russian Academy of Sciences
| | | | - Amiran Sh. Revishvili
- A.V. Vishnevsky National Medical Research Center of Surgery; Russian Medical Academy of Continuous Professional Education
| | - Igor E. Khatkov
- Moscow Clinical/research Center named after A.S. Loginov" of the Moscow Department of Health
| | | | | | | | | | - Olga V. Khlynova
- Perm State Medical University named after Academician E.A. Wagner" of the Ministry of Health of Russia
| | | | | | | | - Olga P. Alekseeva
- Nizhny Novgorod Regional Clinical Hospital named after N.A. Semashko
| | | | - Ivan S. Anosov
- Ryzhikh National Medical Research Center of Coloproctology
| | - Igor G. Bakulin
- I.I. Mechnikov Northwestern State Medical University of the Ministry of Health of Russia
| | - Olga Yu. Barysheva
- Petrozavodsk State University of the Ministry of Education and Science of Russia
| | | | - Viktor V. Veselov
- Ryzhikh National Medical Research Center of Coloproctology; Russian Medical Academy of Continuous Professional Education
| | | | | | | | | | - Anna V. Kagramanova
- Moscow Clinical/research Center named after A.S. Loginov" of the Moscow Department of Health
| | | | - Oleg V. Knyazev
- Moscow Clinical/research Center named after A.S. Loginov" of the Moscow Department of Health
| | | | | | | | | | | | | | | | | | - Alfia H. Odintsova
- Clinical Hospital of the Ministry of Health of the Republic of Tatarstan
| | | | | | | | | | | | | | | | - Stanislav I. Sitkin
- I.I. Mechnikov Northwestern State Medical University of the Ministry of Health of Russia
| | - Maria I. Skalinskaya
- I.I. Mechnikov Northwestern State Medical University of the Ministry of Health of Russia
| | - Andrey N. Surkov
- Reseach Instinute of Pediatrics and Child Health Protection of the Central Clinical Hospital of the Russian Academy of Sciences
| | | | | | | | | | | | - Oleg S. Shifrin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | | | - Oksana B. Shchukina
- First St. Petersburg State Medical University named after Academician I.P. Pavlov
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Dubinsky M, Ma C, Griffith J, Crowell M, Neimark E, Kligys K, O'Connell T. Matching-Adjusted Indirect Comparison Between Risankizumab and Ustekinumab for Induction and Maintenance Treatment of Moderately to Severely Active Crohn's Disease. Adv Ther 2023; 40:3896-3911. [PMID: 37368103 PMCID: PMC10427520 DOI: 10.1007/s12325-023-02546-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 05/09/2023] [Indexed: 06/28/2023]
Abstract
INTRODUCTION Risankizumab (RZB) and ustekinumab (UST), interleukin (IL)-23 and IL-12/23 inhibitors, respectively, are approved treatments for moderately to severely active Crohn's disease (CD); direct comparison between the two is ongoing. We indirectly compared efficacy of RZB versus UST using data from phase 3 trials (RZB: NCT03104413; NCT03105128; NCT03105102; UST: NCT01369329; NCT01369342; NCT01369355). METHODS Matching-adjusted indirect comparison was conducted using individual patient-level data from RZB trials and published aggregated data from UST trials. During induction, patients received RZB 600 mg intravenous (IV) at weeks 0, 4, and 8 or a single dose of UST 6 mg/kg IV at week 0. During maintenance, patients received RZB 180 or 360 mg subcutaneous (SC) or UST 90 mg SC every 8 or 12 weeks to 52 weeks. Outcomes included proportion of patients achieving Crohn's Disease Activity Index (CDAI) response (decrease of ≥ 100 points or total score < 150) or remission (CDAI ≤ 150) and endoscopic improvement (measured by the Simple Endoscopic Score in CD [SES-CD]; response, ≥ 50% reduction from baseline; remission, SES-CD ≤ 2) following induction/baseline. RESULTS Higher proportions of patients achieved clinical and endoscopic outcomes with RZB vs. UST induction treatment, resulting in significantly (p ≤ 0.05) greater percent differences (95% confidence intervals) between groups for CDAI remission (15% [5%, 25%]) and endoscopic response (26% [13%, 40%]) and remission (9% [0%, 19%]). Following maintenance, rates of CDAI remission were similar (range - 0.3% to - 5.0%) for RZB vs. UST. Differences for endoscopic response and remission ranged from 9.3% to 27.7% and 11.6% to 12.5%, respectively; differences were significant (p < 0.05) for endoscopic response for both doses of RZB compared to UST 12-week dosing. CONCLUSIONS This indirect comparison demonstrated higher rates of clinical and endoscopic outcomes during induction for RZB compared to UST; CDAI remission following maintenance was comparable. Direct comparisons of RZB and UST are warranted to validate these findings.
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Affiliation(s)
- Marla Dubinsky
- Department of Pediatrics, Susan and Leonard Feinstein IBD Center, Icahn School of Medicine, Mount Sinai, New York, NY, USA
| | - Christopher Ma
- Division of Gastroenterology & Hepatology, Departments of Medicine & Community Health Sciences, University of Calgary, Calgary, AB, Canada
| | | | | | | | | | - Tom O'Connell
- Medicus Economics LLC, 2 Stonehill Lane, Milton, MA, 02186, USA.
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Saleh A, Abraham BP. Utility of Intestinal Ultrasound in Clinical Decision-Making for Inflammatory Bowel Disease. CROHN'S & COLITIS 360 2023; 5:otad027. [PMID: 37292105 PMCID: PMC10246583 DOI: 10.1093/crocol/otad027] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Indexed: 06/10/2023] Open
Abstract
Background There is a clinical need to improve the monitoring of inflammatory bowel disease (IBD) activity. Despite being used regularly in European countries, intestinal ultrasound (IUS) has been implemented less in the United States for unclear reasons. Aims The aim of this study is to illustrate how IUS can be used as a clinical decision-making tool in an American IBD cohort. Methods This retrospective cohort analysis evaluated patients with IBD seen at our institution who underwent IUS as part of routine evaluation of their IBD from July 2020 to March 2022. To evaluate the clinical utility of IUS for different patient populations and against more frequently used measures of inflammation, we compared patient demographics, inflammatory markers, clinical scores, and medications between patients in remission and those with active inflammation. Treatment plans between the 2 groups were compared and we analyzed patients with follow-up IUS visits to validate treatment plan decisions at initial evaluation. Results Out of 148 total patients with IUS, we found that 62.1% (N = 92) of our patients had active disease and 37.9% (N = 56) were in remission. Ulcerative colitis activity index and Mayo scores were both significantly correlated with IUS findings. The treatment plan was significantly correlated with IUS findings (P = .004). At follow-up, we observed an overall decrease in intestinal thickening, improvements in vascular flow, and mural stratification. Conclusions Clinical decisions incorporating IUS findings effectively reduced inflammation in our IBD patients. IUS should be strongly considered by IBD clinicians in the United States for monitoring disease activity in IBD.
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Affiliation(s)
- Adam Saleh
- Address correspondence to: Adam Saleh, BS, Engineering Medicine, Texas A&M Health Science Center, 1020 Holcombe Boulevard, Houston, TX 77030, USA ()
| | - Bincy P Abraham
- Division of Gastroenterology and Hepatology, Department of Medicine, Lynda K and David M Underwood Center for Digestive Disorders, Houston Methodist Hospital, Houston, Texas, USA
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Santos HO, Martins CEC, Forbes SC, Delpino FM. A Scoping Review of Vitamin D for Nonskeletal Health: A Framework for Evidence-based Clinical Practice. Clin Ther 2023; 45:e127-e150. [PMID: 37080887 DOI: 10.1016/j.clinthera.2023.03.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 03/21/2023] [Accepted: 03/24/2023] [Indexed: 04/22/2023]
Abstract
BACKGROUND Low serum 25-hydroxy-vitamin D [25(OH)D] levels are prevalent worldwide. Although the benefits of vitamin D supplementation have focused on skeletal disorders (eg, rickets, osteomalacia, osteoporosis), emerging evidence for nonskeletal health merits further discussion. PURPOSE The purpose of this review was to critically examine the vitamin D supplementation literature pertaining to nonskeletal health to help guide clinicians. METHODS A scoping review that included observational studies and randomized clinical trials (RCTs) was performed. Evidence from meta-analyses and individual RCTs are discussed, and controversies and future directions are considered. FINDINGS 25(OH)D deficiency is a ubiquitous condition associated with multiple nonskeletal diseases, including cardiometabolic (heart disease, diabetes, and kidney disease), immune (HIV/AIDS and cancer), lung (from traditional chronic disorders to coronavirus disease 2019), and gut diseases. Vitamin D deficiency also affects health across the life span (children, pregnant, and elderly), mental illness, and reproduction in both men and women. In contrast, vitamin D supplementation does not necessarily improve major medical outcomes, even when low 25(OH)D levels are treated. Screening for 25(OH)D status remains an important practice, primarily for high-risk patients (eg, elderly, women with osteoporosis, people with low exposure to sunlight). It is reasonable to supplement with vitamin D to treat 25(OH)D deficiency, such that if beneficial nonskeletal health occurs, this may be considered as a coadjutant instead of the central tenet of the disease. Furthermore, optimizing dosing regimens is an important clinical consideration. IMPLICATIONS Although 25(OH)D deficiency is prevalent in nonskeletal diseases, there is no uniform evidence that vitamin D supplementation improves major medical outcomes, even when low 25(OH)D levels are corrected. Findings from RCTs warrant caution due to possible selection bias. Overall, vitamin D supplementation must be guided by circulating levels as a reasonable medical practice to correct 25(OH)D deficiency.
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Affiliation(s)
- Heitor O Santos
- School of Medicine, Federal University of Uberlandia (UFU), Uberlandia, Minas Gerais, Brazil.
| | | | - Scott C Forbes
- Department of Physical Education Studies, Brandon University, Brandon, Manitoba, Canada
| | - Felipe M Delpino
- Postgraduate in Nursing, Federal University of Pelotas (UFPel), Pelotas, Rio Grande do Sul, Brazil
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Wang G, Tandon P, Rodriguez N, Ambrosio L, Sutton RT, Dieleman LA, Kroeker KI, Huang V. Impact of Disease Activity and Inflammatory Bowel Disease Subtype on Quality of Life in Preconception and Pregnant Patients. Dig Dis Sci 2023; 68:1156-1166. [PMID: 35930124 DOI: 10.1007/s10620-022-07638-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Accepted: 07/19/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) and pregnancy both impact health-related quality of life (HRQoL). However, little is known about IBD-related HRQoL around pregnancy. AIMS To assess the trajectory and predictors of HRQoL in preconception and pregnant patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS Preconception and pregnant patients with IBD were followed prospectively from preconception to twelve months postpartum at a tertiary referral centre. Participants completed the Short IBD Questionnaire (SIBDQ) and were assessed for clinical disease activity (modified Harvey Bradshaw Index or partial Mayo score) and objective disease activity (C-reactive protein [CRP], fecal calprotectin [FCP]). RESULTS A total of 61 patients with IBD (25 CD, 36 UC) were included. During preconception, patients with UC had higher SIBDQ bowel and social sub-scores than those with CD, but this reversed during postpartum. Patients with CD but not UC developed a significant, sustained improvement in SIBDQ upon becoming pregnant, which persisted into 12 months postpartum. In a multivariable linear regression model, clinical disease activity negatively predicted SIBDQ at every pregnancy timepoint and up to 12 months postpartum. SIBDQ was significantly lower in patients with CRP ≥ 8.0 mg/L during trimester 1 (T1), but not later in pregnancy. SIBDQ bowel sub-scores were significantly lower in patients with FCP ≥ 250 mg/kg at T2, T3, and 6 months postpartum. CONCLUSIONS Clinical disease activity is a consistent negative predictor of HRQoL from conception to 12 months postpartum. Patients with UC experience better preconception HRQoL but suffer worse postpartum HRQoL than those with CD.
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Affiliation(s)
- Grace Wang
- Faculty of Medicine, University of Toronto, 1 King's College Cir, Toronto, M5S 1A8, Canada.
| | - Parul Tandon
- Faculty of Medicine, University of Toronto, 1 King's College Cir, Toronto, M5S 1A8, Canada
- Department of Gastroenterology, Mount Sinai Hospital, 600 University Ave, Toronto, M5G 1X5, Canada
| | - Nicole Rodriguez
- Faculty of Medicine, University of Alberta, 8440 112 St NW, Edmonton, T6G 2R7, Canada
| | - Lindsy Ambrosio
- Faculty of Medicine, University of Alberta, 8440 112 St NW, Edmonton, T6G 2R7, Canada
- Division of Gastroenterology, Zeidler Ledcor Centre, University of Alberta, 8540 112 St NW, Edmonton, T6G 2X8, Canada
| | - Reed T Sutton
- Faculty of Medicine, University of Alberta, 8440 112 St NW, Edmonton, T6G 2R7, Canada
- Division of Gastroenterology, Zeidler Ledcor Centre, University of Alberta, 8540 112 St NW, Edmonton, T6G 2X8, Canada
| | - Levinus A Dieleman
- Faculty of Medicine, University of Alberta, 8440 112 St NW, Edmonton, T6G 2R7, Canada
- Division of Gastroenterology, Zeidler Ledcor Centre, University of Alberta, 8540 112 St NW, Edmonton, T6G 2X8, Canada
| | - Karen I Kroeker
- Faculty of Medicine, University of Alberta, 8440 112 St NW, Edmonton, T6G 2R7, Canada
- Division of Gastroenterology, Zeidler Ledcor Centre, University of Alberta, 8540 112 St NW, Edmonton, T6G 2X8, Canada
| | - Vivian Huang
- Faculty of Medicine, University of Toronto, 1 King's College Cir, Toronto, M5S 1A8, Canada
- Department of Gastroenterology, Mount Sinai Hospital, 600 University Ave, Toronto, M5G 1X5, Canada
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Chirra P, Sharma A, Bera K, Cohn HM, Kurowski JA, Amann K, Rivero MJ, Madabhushi A, Lu C, Paspulati R, Stein SL, Katz JA, Viswanath SE, Dave M. Integrating Radiomics With Clinicoradiological Scoring Can Predict High-Risk Patients Who Need Surgery in Crohn's Disease: A Pilot Study. Inflamm Bowel Dis 2023; 29:349-358. [PMID: 36250776 PMCID: PMC9977224 DOI: 10.1093/ibd/izac211] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND Early identification of Crohn's disease (CD) patients at risk for complications could enable targeted surgical referral, but routine magnetic resonance enterography (MRE) has not been definitively correlated with need for surgery. Our objective was to identify computer-extracted image (radiomic) features from MRE associated with risk of surgery in CD and combine them with clinical and radiological assessments to predict time to intervention. METHODS This was a retrospective single-center pilot study of CD patients who had an MRE within 3 months prior to initiating medical therapy. Radiomic features were extracted from annotated terminal ileum regions on MRE and combined with clinical variables and radiological assessment (via Simplified Magnetic Resonance Index of Activity scoring for wall thickening, edema, fat stranding, ulcers) in a random forest classifier. The primary endpoint was high- and low-risk groups based on need for surgery within 1 year of MRE. The secondary endpoint was time to surgery after treatment. RESULTS Eight radiomic features capturing localized texture heterogeneity within the terminal ileum were significantly associated with risk of surgery within 1 year of treatment (P < .05); yielding a discovery cohort area under the receiver-operating characteristic curve of 0.67 (n = 50) and validation cohort area under the receiver-operating characteristic curve of 0.74 (n = 23). Kaplan-Meier analysis of radiomic features together with clinical variables and Simplified Magnetic Resonance Index of Activity scores yielded the best hazard ratio of 4.13 (P = (7.6 × 10-6) and concordance index of 0.71 in predicting time to surgery after MRE. CONCLUSIONS Radiomic features on MRE may be associated with risk of surgery in CD, and in combination with clinicoradiological scoring can yield an accurate prognostic model for time to surgery.
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Affiliation(s)
- Prathyush Chirra
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA
| | - Anamay Sharma
- Division of Gastroenterology, Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Kaustav Bera
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA
- Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - H Matthew Cohn
- Long Island Digestive Disease Consultants, Northwell Health Physician Partners, Setauket, NY, USA
| | - Jacob A Kurowski
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, OH, USA
| | - Katelin Amann
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA
| | - Marco-Jose Rivero
- Division of Gastroenterology, Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Anant Madabhushi
- Wallace H. Coulter Department of Biomedical Engineering, Radiology and Imaging Sciences, Biomedical Informatics (BMI) and Pathology, Georgia Institute of Technology and Emory University, Atlanta, GA, USA
- Research Health Scientist, Atlanta Veterans Administration Medical Center, Atlanta, GA, USA
| | - Cheng Lu
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA
| | - Rajmohan Paspulati
- Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Sharon L Stein
- Department of General Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH, USAand
| | - Jeffrey A Katz
- Division of Gastroenterology, Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Satish E Viswanath
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA
| | - Maneesh Dave
- Division of Gastroenterology, Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, UC Davis Medical Center, UC Davis School of Medicine, Sacramento, CA, USA
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Abstract
BACKGROUND Real-world data showed that ustekinumab is an effective treatment for Crohn's disease for up to 52 weeks. Yet, long-term effectiveness and safety outcomes beyond 52 weeks are limited. This study aimed to evaluate the corticosteroid-free clinical remission for up to 104 weeks. Secondary aims were focused on biochemical disease, dosing adjustments and safety outcomes. METHODS This multicentre prospective cohort study enrolled Crohn's disease patients who started ustekinumab between May 2016 and September 2019. Participants had scheduled outpatient visits at week 0, 13, 26, 52 and 104. Data on clinical disease [Harvey Bradshaw Index (HBI) = 4 points = remission], biochemical disease (faecal calprotectin = 200 µg/g or C-reactive protein = 10 mg/l = remission), dose adjustments and adverse drug reactions (ADRs) were recorded. RESULTS We included 101 Crohn's disease patients. In all patients, the proportion of patients in corticosteroid-free clinical remission was 35 and 36% at week 52 and 104. Of patients achieving corticosteroid-free remission at week 52, more than half maintained corticosteroid-free remission throughout week 104. Biochemical remission rates were 25 and 30% at week 52 and 104, respectively. In the first year of treatment, 33% required their first dose escalation, and 15% in the second year. Overall, 7% of patients discontinued ustekinumab due to ADRs. Ustekinumab persistency rates were 68% at week 52 and 59% at week 104. CONCLUSION Ustekinumab is an effective and well-tolerated treatment for Crohn's disease. More than half of all patients continued ustekinumab treatment after 104 weeks whereas one-third achieved corticosteroid-free remission.
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Stallhofer J, Guse J, Kesselmeier M, Grunert PC, Lange K, Stalmann R, Eckardt V, Stallmach A. Immunomodulator comedication promotes the reversal of anti-drug antibody-mediated loss of response to anti-TNF therapy in inflammatory bowel disease. Int J Colorectal Dis 2023; 38:54. [PMID: 36840779 PMCID: PMC9968255 DOI: 10.1007/s00384-023-04349-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/13/2023] [Indexed: 02/26/2023]
Abstract
PURPOSE Loss of therapeutic response (LOR) due to anti-drug antibodies (ADA) against tumor necrosis factor (TNF) inhibitors is common in patients with inflammatory bowel disease (IBD). We aimed to investigate whether immunomodulator comedication can reverse the immunogenic LOR to TNF inhibitors in IBD. METHODS In this real-world retrospective cohort study, 123 IBD patients with neutralizing ADA to infliximab or adalimumab and concomitant subtherapeutic trough levels were screened for clinical LOR. Subsequent ADA and trough level measurements and clinical outcomes were analyzed for patients who received either immunomodulator comedication or dose intensification of infliximab or adalimumab to overcome LOR. RESULTS Following immunogenic LOR, the initial anti-TNF regimen was optimized in 33 patients. In univariable and multivariable logistic regression analyses, immunomodulator comedication was identified as the crucial factor for regaining clinical remission and ADA clearance. Detectable trough levels (≥ 0.98 or ≥ 1.00 mg/L, respectively) had optimal predictive performance for both endpoints in receiver operating characteristics curves [area under the curve 0.86 (95% confidence interval 0.68-1.00) for regaining clinical remission, 0.87 (0.71-1.00) for ADA clearance]. Furthermore, 11/20 patients (55%) on a comedication with azathioprine or methotrexate and 2/13 patients (15%) receiving anti-TNF dose intensification exclusively (P = 0.032) exhibited ADA elimination, regain of therapeutic trough levels, and clinical remission. Regain of clinical remission alone was achieved in 17/20 (85%) patients receiving comedication and 2/13 (15%) patients receiving anti-TNF dose intensification (P = 1.6 × 10-4). CONCLUSION Immunogenic LOR to infliximab or adalimumab in IBD can be successfully reversed using immunomodulator comedication.
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Affiliation(s)
- Johannes Stallhofer
- Department of Internal Medicine IV (Gastroenterology, Hepatology and Infectious Diseases), Jena University Hospital, Am Klinikum 1, Jena, 07747, Germany.
| | - Jan Guse
- Department of Internal Medicine IV (Gastroenterology, Hepatology and Infectious Diseases), Jena University Hospital, Am Klinikum 1, Jena, 07747, Germany
| | - Miriam Kesselmeier
- Institute of Medical Statistics, Computer and Data Sciences, Jena University Hospital, Jena, Germany
| | - Philip Christian Grunert
- Department of Internal Medicine IV (Gastroenterology, Hepatology and Infectious Diseases), Jena University Hospital, Am Klinikum 1, Jena, 07747, Germany
| | - Kathleen Lange
- Department of Internal Medicine IV (Gastroenterology, Hepatology and Infectious Diseases), Jena University Hospital, Am Klinikum 1, Jena, 07747, Germany
| | - Robert Stalmann
- Institute of Clinical Chemistry and Laboratory Diagnostics, Centralized Diagnostic Laboratory Services, Jena University Hospital, Jena, Germany
| | - Verena Eckardt
- Institute of Clinical Chemistry and Laboratory Diagnostics, Centralized Diagnostic Laboratory Services, Jena University Hospital, Jena, Germany
| | - Andreas Stallmach
- Department of Internal Medicine IV (Gastroenterology, Hepatology and Infectious Diseases), Jena University Hospital, Am Klinikum 1, Jena, 07747, Germany
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Nakase H, Esaki M, Hirai F, Kobayashi T, Matsuoka K, Matsuura M, Naganuma M, Saruta M, Tsuchiya K, Uchino M, Watanabe K, Hisamatsu T, the TRADE consensus group AndohAkiraBambaShigekiEsakiMotohiroFujiyaMikihiroFutamiKitaroHataKeisukeHiraiFumihitoHiraokaSakikohttp://orcid.org/0000-0002-1178-3536HisamatsuTadakazuHokariRyotaIshiharaShunjiIshiharaSoichiroItabashiMichioKakutaYoichiKatoJunKatoShingoKatsuradaTakehikoKitamuraKazuyaKobayashiKiyonoriKobayashiTakuKoganeiKazutakaMaemotoAtsuoMatsuiToshiyukiMatsumotoTakayukiMatsuokaKatsuyoshiMatsuuraMinoruMotoyaSatoshiNagahoriMasakazuNaganumaMakotoNaitoYujiNakamuraShiroNakaseHiroshiOgataHaruhikoOkazakiKazuichiSakurabaHirotakeSarutaMasayukiShinzakiShinichiroSugimotoKenSugitaAkiraSuzukiYasuoTakahashiKenichiTakagiTomohisaTakenakaKentoTakeuchiKenTsuchiyaKiichiroTsujikawaTomoyukiUchinoMotoiUenoFumiakiWatanabeKenjiWatanabeMamoruYamamotoTakayukiYokoyamaKaoruYoshidaAtsushiYoshimuraNaoki. Treatment escalation and de-escalation decisions in Crohn's disease: Delphi consensus recommendations from Japan, 2021. J Gastroenterol 2023; 58:313-345. [PMID: 36773075 PMCID: PMC10050046 DOI: 10.1007/s00535-023-01958-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 01/08/2023] [Indexed: 02/12/2023]
Abstract
BACKGROUND We aimed to develop criteria for treatment intensification in patients with (1) luminal Crohn's disease (CD), (2) CD with perianal disease and/or fistula, (3) CD with small bowel stenosis, (4) in the postoperative setting, and (5) for discontinuing or reducing the dose of treatment in patients with CD. METHODS PubMed and Embase were searched for studies published since 1998 which may be relevant to the five defined topics. Results were assessed for relevant studies, with preference given to data from randomized, controlled studies. For each question, a core panel of 12 gastroenterologists defined the treatment target and developed statements, based on the literature, current guidelines, and relevant additional studies. The evidence supporting each statement was graded using the Oxford Centre for Evidence-Based Medicine: Levels of Evidence (March 2009). A modified Delphi process was used to refine statements and gain agreement from 54 Japanese specialists at in-person and online meetings conducted between October 2020 and April 2021. RESULTS Seventeen statements were developed for treatment intensification in luminal CD (targeting endoscopic remission), six statements for treatment intensification in perianal/fistulizing CD (targeting healing of perianal lesions and complete closure of the fistula), six statements for treatment intensification in CD with small bowel stenosis (targeting resolution of obstructive symptoms), seven statements for treatment intensification after surgery (targeting endoscopic remission), and five statements for discontinuing or reducing the dose of treatment in patients with CD. CONCLUSIONS These statements provide guidance on how and when to intensify or de-intensify treatment for a broad spectrum of patients with CD.
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Affiliation(s)
- Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-Ku, Sapporo, Hokkaido 060-8543 Japan
| | - Motohiro Esaki
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan
| | - Fumihito Hirai
- Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
| | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University, Kitasato Institute Hospital, Tokyo, Japan
| | - Katsuyoshi Matsuoka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Sakura Medical Center, Sakura, Chiba Japan
| | - Minoru Matsuura
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-Shi, Tokyo, 181-8611 Japan
| | - Makoto Naganuma
- Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Masayuki Saruta
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Kiichiro Tsuchiya
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Motoi Uchino
- Division of Inflammatory Bowel Disease, Department of Gastroenterological Surgery, Hyogo Medical University, Nishinomiya, Hyogo Japan
| | - Kenji Watanabe
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo Medical University, Nishinomiya, Hyogo Japan
| | - Tadakazu Hisamatsu
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-Shi, Tokyo, 181-8611 Japan
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Grigorescu RR, Husar-Sburlan IA, Rosulescu G, Bobirca A, Cerban R, Bobirca F, Florescu MM. Pregnancy in Patients with Inflammatory Bowel Diseases-A Literature Review. Life (Basel) 2023; 13:475. [PMID: 36836832 PMCID: PMC9961380 DOI: 10.3390/life13020475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 02/03/2023] [Accepted: 02/04/2023] [Indexed: 02/11/2023] Open
Abstract
In recent years, we have faced an increasing incidence of inflammatory bowel disease (IBD), especially among young people, affecting them during their reproductive years. The paucity of data and reduced knowledge regarding the evolution of the disease during pregnancy and the adverse effects of the therapy on the mother and infant increase voluntary childlessness in this group of patients. Depending on the type of IBD, severity and surgical or medical management, this can negatively affect the pregnancy. C-sections and the risk of low-birth-weight babies are higher in women with IBD, independent of active/inactive disease, while preterm birth, stillbirth and miscarriage are associated with disease activity. In the last period, medicinal therapy has evolved, and new molecules have been developed for better control of the lesions, but the effect on pregnancy and breastfeeding is still controversial. We conducted this review by studying the literature and recent research in order to have a better image of the practical management of IBD during pregnancy.
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Affiliation(s)
| | | | - Georgiana Rosulescu
- Gastroenterology Department, “Sfanta Maria” Hospital, 011172 Bucharest, Romania
| | - Anca Bobirca
- Department of Internal Medicine and Rheumatology, Dr. I. Cantacuzino Clinical Hospital, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Razvan Cerban
- Center for Digestive Disease and Liver Transplantation, Fundeni Clinical Institute, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Florin Bobirca
- Surgery Department, Dr. Ion Cantacuzino Clinical Hospital, 011437 Bucharest, Romania
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Wu EH, Guo Z, Zhu WM. Postoperative diarrhea in Crohn's disease: Pathogenesis, diagnosis, and therapy. World J Clin Cases 2023; 11:7-16. [PMID: 36687182 PMCID: PMC9846968 DOI: 10.12998/wjcc.v11.i1.7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Revised: 12/08/2022] [Accepted: 12/23/2022] [Indexed: 01/04/2023] Open
Abstract
Diarrhea is a frequent symptom in postoperative patients with Crohn's diseases (CD), and several different mechanisms likely account for postoperative diarrhea in CD. A targeted strategy based on a comprehensive understanding of postoperative diarrhea is helpful for better postoperative recovery.
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Affiliation(s)
- En-Hao Wu
- Department of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu Province, China
| | - Zhen Guo
- Department of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu Province, China
| | - Wei-Ming Zhu
- Department of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu Province, China
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Chebli JMF, Parra RS, Flores C, Moraes AC, Nones RB, Gomes TNF, Perdomo AMB, Scapini G, Zaltman C. Effectiveness and Safety of Ustekinumab for Moderate to Severely Active Crohn's Disease: Results from an Early Access Program in Brazil. J Clin Med 2022; 11:6481. [PMID: 36362709 PMCID: PMC9654680 DOI: 10.3390/jcm11216481] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 10/04/2022] [Accepted: 10/06/2022] [Indexed: 11/06/2022] Open
Abstract
This prospective, observational, open-label study aimed to provide access to ustekinumab prior to market authorization and assess its safety and effectiveness in patients with Crohn's disease (CD) refractory to anti-tumor necrosis factor-α and conventional drugs in Brazil. Patients with a diagnosis of moderate-to-severe active CD for ≥3 months before screening received ustekinumab in a single intravenous induction dose (~6 mg/kg) at week 0, and a 90 mg maintenance dose, subcutaneously, every 8 or 12 weeks, from week 8 through to 80. Serious adverse events (SAE), adverse drug reactions (ADR), clinical response (per CD Activity Index and Harvey Bradshaw Index (HBI) scores), remission (per HBI scores), biomarkers (C-reactive protein (CRP) and fecal calprotectin (FC)) and endoscopic improvement rate over 80 weeks were assessed. Patients with a mean age of 39.9 years were assessed. Discontinuation rate was low (23%) and most adverse events were mild (68.7%). The SAE rate was 21% (mostly infections/infestations or gastrointestinal disorder), and ADR rate was 44%. The CD Activity Index and HBI scores decreased (by 74% and 81%, respectively) with 50% of patients showing normalized CRP and FC, and 63% achieved endoscopic improvement. Ustekinumab was fairly safe, well tolerated and effective in a Brazilian cohort of CD patients.
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Affiliation(s)
| | - Rogério Serafim Parra
- Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto 14049-900, Brazil
| | - Cristina Flores
- Reference Center in Crohn and Colitis, Digestive System Institute, Rio Grande do Sul 90560-002, Brazil
| | | | - Rodrigo Bremer Nones
- Gastroenterology Unit, Hospital of Nossa Senhora das Graças, Curitiba 80810-040, Brazil
| | | | | | - Gustavo Scapini
- Johnson-Johnson and Internal Former Janssen-Cilag Pharmaceutical, São Paulo 04543-011, Brazil
| | - Cyrla Zaltman
- Internal Medicine Department, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro 21941-617, Brazil
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Bamola VD, Dubey D, Samanta P, Kedia S, Ahuja V, Madempudi RS, Neelamraju J, Chaudhry R. Role of a probiotic strain in the modulation of gut microbiota and cytokines in inflammatory bowel disease. Anaerobe 2022; 78:102652. [PMID: 36198385 DOI: 10.1016/j.anaerobe.2022.102652] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 09/24/2022] [Accepted: 09/26/2022] [Indexed: 11/27/2022]
Abstract
OBJECTIVE To assess the effect of a probiotic strain Bacillus clausii UBBC-07 on gut microbiota and cytokines in IBD patients. METHOD Patients were randomly allocated to either placebo or probiotic Bacillus clausii UBBC-07 for four weeks along with the standard medical treatment (SMT). Enrolled patients were evaluated before and after intervention for presence of the given probiotic, change in gut microbiota, change in serum cytokines, serotonin and dopamine, symptoms of disease, physical, behavioral and psychological parameters. RESULTS Probiotic strain Bacillus clausii UBBC-07 showed good survival in IBD patients in the treatment group (p < 0.01) without any reported adverse event. Metagenomic analysis showed that the given probiotic strain was able to modulate the gut microbiota in treated group. Phylum Firmicutes was increased and phylum Bacteroidetes was decreased in the probiotic treated group. A significant increase was observed in the abundance of anaerobic bacterial genera Lactobacillus, Bifidobacterium and Faecalibacterium in the probiotic treated group (p < 0.01) as compared to placebo group. Significant increase was observed in IL-10 (p < 0.05) and variable decrease in the secretion of IL-1β, TNF- α, IL-6, IL -17 and IL -23 in probiotic treated group. In the treatment group a significant decrease in the symptoms of IBD and improvement in the psychological parameter to various degrees was noted. CONCLUSION These results indicated that probiotic strain B clausii UBBC-07 affected the gut microbiota and cytokine secretion and shown efficacy in IBD patients.
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Affiliation(s)
- V Deepak Bamola
- Department of Microbiology, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Divya Dubey
- Department of Microbiology, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Projoyita Samanta
- Department of Microbiology, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Saurabh Kedia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Vineet Ahuja
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Ratna Sudha Madempudi
- Centre for Research & Development, Unique Biotech Ltd., Plot No. 2, Phase-II, Alexandria Knowledge Park, Hyderabad, Telangana, 500078, India
| | - Jayanthi Neelamraju
- Centre for Research & Development, Unique Biotech Ltd., Plot No. 2, Phase-II, Alexandria Knowledge Park, Hyderabad, Telangana, 500078, India
| | - Rama Chaudhry
- Department of Microbiology, All India Institute of Medical Sciences, New Delhi, 110029, India.
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Castro PCSD, Magro DO, Nones RB, Furlan TK, Miranda EF, Kotze PG. USTEKINUMAB IN CROHN'S DISEASE MANAGEMENT: A BRAZILIAN OBSERVATIONAL STUDY. ARQUIVOS DE GASTROENTEROLOGIA 2022; 59:S0004-28032022005001206. [PMID: 36515346 DOI: 10.1590/s0004-2803.202204000-89] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 08/04/2022] [Indexed: 11/16/2022]
Abstract
BACKGROUND Real-world data on the use of Ustekinumab (UST) in Brazilian and Latin American patients with Crohn's disease (CD) are scarce. OBJECTIVE The primary endpoint was assessment of clinical remission at weeks 8 and 52, and secondary endpoints were: assessment of clinical response at weeks 8 and 52, endoscopic remission, adverse events, and rates of CD-related abdominal surgery during follow-up. METHODS observational and retrospective study, including patients with CD treated at two centers, who received UST at any time during their treatment. Remission and clinical response were defined as a Harvey-Bradshaw index ≤4 and ≥3 points reduction, respectively. RESULTS Seventy-four patients were included, 85.1% previously exposed to anti-TNFs. Clinical remission was observed in 45.8% and 59.4% of patients at weeks 8 and 52, respectively. The clinical response rates were 54.2% and 67.6% at weeks 8 and 52. Endoscopic remission was observed in 21.8% of patients. Seventeen patients had adverse events, mostly mild infections, with 22.9% of patients undergoing abdominal surgery (ileocolectomy being the most common procedure). CONCLUSION UST therapy resulted in significant rates of remission and clinical response, as described in other real-world studies. Few patients had adverse events during treatment, showing its adequate safety profile.
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Affiliation(s)
- Paula Cenira Senger de Castro
- Pontifícia Universidade Católica do Paraná, Faculdade de Medicina, Programa de Pós-Graduação em Ciências da Saúde, Curitiba, PR, Brasil
| | - Daniéla Oliveira Magro
- Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Departamento de Cirurgia, Campinas, PR, Brasil
| | - Rodrigo Bremer Nones
- Pontifícia Universidade Católica do Paraná, Faculdade de Medicina, Programa de Pós-Graduação em Ciências da Saúde, Curitiba, PR, Brasil
| | - Thaisa Kowalski Furlan
- Universidade Federal do Paraná, Hospital de Clínicas, Departamento de Gastroenterologia, Curitiba, PR, Brasil
| | - Eron Fábio Miranda
- Pontifícia Universidade Católica do Paraná, Faculdade de Medicina, Programa de Pós-Graduação em Ciências da Saúde, Curitiba, PR, Brasil
| | - Paulo Gustavo Kotze
- Pontifícia Universidade Católica do Paraná, Faculdade de Medicina, Programa de Pós-Graduação em Ciências da Saúde, Curitiba, PR, Brasil
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Kumar P, Vuyyuru SK, Kante B, Kedia S, Sahu P, Ranjan MK, Mundhra S, Golla R, Kumar M, Virmani S, Gupta A, Yadav N, Makharia G, Ahuja V. Efficacy and safety of biosimilar versus originator infliximab in patients with inflammatory bowel disease: A real-world cohort analysis. Indian J Gastroenterol 2022; 41:446-455. [PMID: 36378484 DOI: 10.1007/s12664-022-01252-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Accepted: 02/01/2022] [Indexed: 11/16/2022]
Abstract
BACKGROUND Anti-tumor necrosis factor (anti-TNF) monoclonal antibody, infliximab, is the primary therapeutic modality for patients with Crohn's disease (CD) and ulcerative colitis (UC), refractory to conventional therapy. Biosimilars of infliximab have been shown to have equivalent efficacy to originator infliximab. We compared the safety and efficacy of infliximab biosimilar with the originator in Indian patients with inflammatory bowel disease (IBD). METHODS Patients with IBD treated with either originator or biosimilar infliximab from January 2005 to October 2020 were included in this retrospective analysis. The safety and efficacy of originator or biosimilar infliximab in inducing and maintaining clinical remission at weeks 14 and 52 for CD and UC were evaluated. Disease activity was estimated at baseline, after induction therapy, after 1 year of treatment, and during 12 months of follow-up. RESULTS In all, 137 patients (82 CD; 55 UC) were included, of whom 102 were on originator, and 35 patients received biosimilar. In biosimilar group, clinical response and remission rates at weeks 14 and 52 were 84.2%, 58% and 68.4%, 52.6% in CD and 81.2%, 56.2% and 68.7%, 62.5% in UC patients, respectively. Among patients who were on originator, clinical response and remission rates at weeks 14 and 52 were 79.4%, 46% and 57.1%, 43% in CD and 72%, 64.1% and 66.7%, 56.4% in UC patients, respectively. Thirty-three (24.1%) patients experienced adverse events; eighteen developed tuberculosis (TB), of whom 17 received originator and one patient received biosimilar. CONCLUSIONS Infliximab biosimilar is comparable to originator infliximab in terms of safety profile and its efficacy in inducing and maintaining remission in patients with IBD.
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Affiliation(s)
- Peeyush Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Sudheer K Vuyyuru
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Bhaskar Kante
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Saurabh Kedia
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Pabitra Sahu
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Mukesh Kumar Ranjan
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Sandeep Mundhra
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Rithvik Golla
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Mukesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Shubi Virmani
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Anvita Gupta
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Nidhi Yadav
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Govind Makharia
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Vineet Ahuja
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India.
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Pray C, Wong ECL, Aruljothy A, Dulai PS, Marshall JK, Reinisch W, Narula N. Ulcer Size After Induction Therapy Performs Better Than Symptom Assessment for Prediction of One Year Endoscopic Remission in Crohn's Disease: A Post Hoc Analysis. Inflamm Bowel Dis 2022:6732190. [PMID: 36179118 DOI: 10.1093/ibd/izac210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND We evaluated whether postinduction ulcer size and patient-reported outcome (PRO) severity are associated with the achievement of 1-year endoscopic remission (ER) in patients with Crohn's disease (CD). METHODS This post hoc analysis combined data from several clinical trials including 283 patients with baseline ulcers ≥5 mm with repeat endoscopy after ustekinumab or adalimumab induction therapy. Patient-reported outcomes including stool frequency (SF) and abdominal pain (AP) were measured by the Crohn's Disease Activity Index. Thresholds of SF ≥4 and/or AP ≥2 indicated moderately to severely active CD. Endoscopic remission was defined as Simple Endoscopic Score for CD (SES-CD) <3. Multivariate logistic regression models adjusted for confounders (including disease duration and treatment allocation) evaluated the relationships between postinduction ulcer size, PRO symptoms, and achievement of 1-year ER. RESULTS Among the 131 CD patients who continued to have ulcers ≥5 mm after induction therapy, 48 (36.6%) achieved 1-year ER. Patients with postinduction ulcers ≥5 mm were approximately 5 times less likely to achieve 1-year ER than the 152 individuals who had small or no postinduction ulcers (odds ratio [OR], 0.20; 95% CI, 0.08-0.51, P = .001). In patients with ulcers ≥5 mm after induction, postinduction PRO scores (including PRO2 and PRO3) did not predict 1-year ER. CONCLUSIONS Crohn's disease patients with ulcers ≥5 mm after induction therapy are less likely to achieve 1-year ER. Postinduction PRO severity does not offer additional prognostic information. This may suggest that objective measures of disease such as endoscopic ulcer size should be considered over symptom assessments for determining clinical response to therapy and utilized in trials for maintenance therapy.
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Affiliation(s)
- Cara Pray
- Department of Medicine, Division of Gastroenterology, and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Emily C L Wong
- Department of Medicine, Division of Gastroenterology, and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Achuthan Aruljothy
- Department of Medicine, Division of Gastroenterology, and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Parambir S Dulai
- Division of Gastroenterology, Northwestern University, Chicago, IL, USA
| | - John K Marshall
- Department of Medicine, Division of Gastroenterology, and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Walter Reinisch
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria
| | - Neeraj Narula
- Department of Medicine, Division of Gastroenterology, and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
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Olaisen M, Richard ML, Beisvåg V, Granlund AVB, Røyset ES, Rué O, Martinsen TC, Sandvik AK, Sokol H, Fossmark R. The ileal fungal microbiota is altered in Crohn's disease and is associated with the disease course. Front Med (Lausanne) 2022; 9:868812. [PMID: 36237548 PMCID: PMC9551188 DOI: 10.3389/fmed.2022.868812] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 09/08/2022] [Indexed: 11/13/2022] Open
Abstract
Introduction Fungal microbiota's involvement in the pathogenesis of Crohn's disease (CD) is incompletely understood. The terminal ileum is a predilection site both for primary involvement and recurrences of CD. We, therefore, assessed the mucosa-associated mycobiota in the inflamed and non-inflamed ileum in patients with CD. Methods The mucosa-associated mycobiota was assessed by ITS2 sequencing in a total of 168 biopsies sampled 5 and 15 cm proximal of the ileocecal valve or ileocolic anastomosis in 44 CD patients and 40 healthy controls (HC). CD patients with terminal ileitis, with endoscopic inflammation at 5 cm and normal mucosa at 15 cm and no history of upper CD involvement, were analyzed separately. The need for additional CD treatment the year following biopsy collection was recorded. Results CD patients had reduced mycobiota evenness, increased Basidiomycota/Ascomycota ratio, and reduced abundance of Chytridiomycota compared to HC. The mycobiota of CD patients were characterized by an expansion of Malassezia and a depletion of Saccharomyces, along with increased abundances of Candida albicans and Malassezia restricta. Malassezia was associated with the need for treatment escalation during follow-up. Current anti-TNF treatment was associated with lower abundances of Basidiomycota. The alpha diversity of the inflamed and proximal non-inflamed mucosa within the same patients was similar. However, the inflamed mucosa had a more dysbiotic composition with increased abundances of Candida sake and reduced abundances of Exophiala equina and Debaryomyces hansenii. Conclusions The ileal mucosa-associated mycobiota in CD patients is altered compared to HC. The mycobiota in the inflamed and proximal non-inflamed ileum within the same patients harbor structural differences which may play a role in the CD pathogenesis. Increased abundance of Malassezia was associated with an unfavorable disease course.
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Affiliation(s)
- Maya Olaisen
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Gastroenterology and Hepatology, St. Olav's Hospital - Trondheim University Hospital, Trondheim, Norway
| | - Mathias L. Richard
- INRAE, AgroParisTech, Micalis Institute, Université Paris-Saclay, Jouy-en-Josas, France
- Paris Center for Microbiome Medicine, Fédération Hospitalo-Universitaire, Paris, France
| | - Vidar Beisvåg
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
- Central Administration, St. Olav's Hospital - Trondheim University Hospital, Trondheim, Norway
| | - Atle van Beelen Granlund
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
- Centre of Molecular Inflammation Research, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
| | - Elin S. Røyset
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
- Centre of Molecular Inflammation Research, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Pathology, St. Olav's Hospital - Trondheim University Hospital, Trondheim, Norway
| | - Olivier Rué
- INRAE, MaIAGE, Université Paris-Saclay, Jouy-en-Josas, France
- INRAE, BioinfOmics, MIGALE Bioinformatics Facility, Université Paris-Saclay, Jouy-en-Josas, France
| | - Tom Christian Martinsen
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Gastroenterology and Hepatology, St. Olav's Hospital - Trondheim University Hospital, Trondheim, Norway
| | - Arne Kristian Sandvik
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Gastroenterology and Hepatology, St. Olav's Hospital - Trondheim University Hospital, Trondheim, Norway
- Centre of Molecular Inflammation Research, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
| | - Harry Sokol
- INRAE, AgroParisTech, Micalis Institute, Université Paris-Saclay, Jouy-en-Josas, France
- Paris Center for Microbiome Medicine, Fédération Hospitalo-Universitaire, Paris, France
- Gastroenterology Department, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Sorbonne Université, Paris, France
| | - Reidar Fossmark
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Gastroenterology and Hepatology, St. Olav's Hospital - Trondheim University Hospital, Trondheim, Norway
- *Correspondence: Reidar Fossmark
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50
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Adedokun OJ, Xu Z, Gasink C, Kowalski K, Sandborn WJ, Feagan B. Population Pharmacokinetics and Exposure-Response Analyses of Ustekinumab in Patients With Moderately to Severely Active Crohn's Disease. Clin Ther 2022; 44:1336-1355. [PMID: 36150926 DOI: 10.1016/j.clinthera.2022.08.010] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 08/16/2022] [Accepted: 08/25/2022] [Indexed: 11/25/2022]
Abstract
PURPOSE Ustekinumab, a fully human immunoglobulin G1κ monoclonal antibody that antagonizes human interleukin-12/23p40, is an effective therapy for several immune-mediated inflammatory diseases, including Crohn's disease (CD). This work characterizes the population pharmacokinetic (PK) and exposure-response (E-R) relationships of ustekinumab in patients with CD using data from four Phase IIb/III clinical studies. METHODS Serum ustekinumab concentration-time data from 1673 patients after IV and/or SC administration of ustekinumab were fitted simultaneously using nonlinear mixed effects modeling to develop a population PK model, which was subsequently used to evaluate simulation scenarios. Logistic regression E-R models were used to assess relationships between serum ustekinumab concentrations and clinical remission after induction (n = 1910) and maintenance (n = 387) treatment. FINDINGS Ustekinumab PK properties are well described by a two-compartment model with first-order absorption and elimination. Typical values of PK parameters for a 70-kg patient were: clearance, 0.192 L/d; volume of distribution at steady state, 4.62 L; and intercompartmental clearance, 0.287 L/d. Ustekinumab terminal elimination t1/2 was 19 days, and bioavailability after SC administration was 78.3%. Ustekinumab clearance was not affected by coadministration of immunosuppressive agents or corticosteroids. Body weight, serum albumin, and C-reactive protein (CRP) concentrations, tumor necrosis factor (TNF) antagonist failure status, sex, race (Asian vs non-Asian), and anti-ustekinumab antibody status significantly affected ustekinumab disposition; however, the effects of these covariates on ustekinumab exposure were not clinically relevant. The population PK model predicts that a milligram/kilogram dosing approach will result in lower ustekinumab exposure in patients with lower body weight. A positive E-R relationship was established between ustekinumab concentration and efficacy outcomes. The treatment effect of ustekinumab after induction therapy was more pronounced among patients with higher baseline CRP concentrations relative to those with lower values. IMPLICATIONS In patients with CD, ustekinumab disposition after IV and SC administration was biexponential and consistent with those in patients with ulcerative colitis. Prior treatment with TNF antagonists or the concomitant use of immunosuppressive agents or corticosteroids had no effect on ustekinumab disposition. None of the covariates that affected ustekinumab clearance had a clinically meaningful impact on ustekinumab exposure. E-R models support recommended posology of ustekinumab in adults with CD; however, an ∼6 mg/kg IV induction dose in pediatric patients with lower body weights may not provide exposure that matches that in adult patients. CLINICALTRIALS gov identifiers: NCT00771667, NCT01369329, NCT01369342, and NCT01369355. (Clin Ther. 2022;44:XXX-XXX) © 2022 Elsevier HS Journals, Inc.
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Affiliation(s)
| | - Zhenhua Xu
- Janssen Research & Development, LLC, Spring House, Pennsylvania, USA
| | | | - Ken Kowalski
- A2PG-Ann Arbor Pharmacometrics Group, Ann Arbor, Michigan, USA
| | - William J Sandborn
- Division of Gastroenterology, University of California San Diego, La Jolla, California, USA
| | - Brian Feagan
- Alimentiv (formerly Robarts Clinical Trials) and Division of Gastroenterology, Department of Medicine, Western University, London, Ontario, Canada
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