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Jun YK, Choi Y, Shin CM, Park YS, Kim N, Lee DH, Ahn S, Yoon H. Impact of early aggressive treatment on long-term biochemical marker patterns in inflammatory bowel disease. J Gastroenterol 2025:10.1007/s00535-025-02244-w. [PMID: 40314771 DOI: 10.1007/s00535-025-02244-w] [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: 01/06/2025] [Accepted: 03/16/2025] [Indexed: 05/03/2025]
Abstract
BACKGROUNDS The disease course of inflammatory bowel disease (IBD) is highly variable; early and precise identification of patients with poor outcomes is crucial. We aimed to classify the long-term disease course of IBD using biochemical markers and evaluate the clinical factors associated with different disease courses. METHODS A latent class mixed model was employed to identify distinct trajectories of C-reactive protein (CRP) and fecal calprotectin (FCP) levels in 256 and 635 patients with Crohn's disease (CD) and ulcerative colitis (UC), respectively, from a tertiary hospital cohort. Multinomial logistic regression was used to evaluate the relationships between various trajectories and clinical variables. RESULTS Three trajectories were identified for CD and UC: class 1, early and sustained biochemical remission; class 2, delayed remission; and class 3, prolonged difficulty in achieving remission for > 5 years. For patients with CD, early immunomodulator initiation was associated with a high likelihood of belonging to class 1 in the CRP trajectory analysis, whereas early advanced therapy increased the probability of belonging to class 1 in the FCP trajectory analysis. CRP trajectory analysis showed no significant associations in patients with UC. Younger age at diagnosis and early immunomodulator initiation were associated with higher odds of being in class 2 or 3, whereas current smoking was associated with a high likelihood of being in class 1 in the FCP trajectory analysis. CONCLUSIONS Early aggressive medical treatment for CD may lead to long-term biochemical remission, whereas no similar association was observed in UC.
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Affiliation(s)
- Yu Kyung Jun
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Yonghoon Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Young Soo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Soyeon Ahn
- Division of Statistics, Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam, South Korea.
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
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Fansiwala K, Spartz EJ, Roney AR, Kwaan MR, Sauk JS, Chen PH, Limketkai BN. Increasing Rates of Bowel Resection Surgery for Stricturing Crohn's Disease in the Biologic Era. Inflamm Bowel Dis 2025; 31:935-943. [PMID: 38795051 PMCID: PMC11985397 DOI: 10.1093/ibd/izae113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Indexed: 05/27/2024]
Abstract
BACKGROUND The era of biologics is associated with declining rates of surgery for Crohn's disease (CD), but the impact on surgery for stricturing CD is unknown. Our study aimed to assess nationwide trends in bowel resection surgery for obstruction in CD since the introduction of infliximab for CD in 1998. METHODS Using the Nationwide Inpatient Sample, we performed a nationwide analysis, identifying patients hospitalized for CD who underwent bowel resection for an indication of obstruction between 1998 and 2020 (era of biologics). Longitudinal trends in all CD-related resections and resection for obstruction were evaluated. Multivariable logistic regression identified patient and hospital characteristics associated with bowel resection surgery for obstruction. RESULTS Hospitalizations for all CD-related resections decreased from 12.0% of all hospitalizations in 1998 to 6.9% in 2020, while hospitalizations for CD-related resection for obstructive indication increased from 1.3% to 2.0%. The proportion of resections for obstructive indication amongst all CD-related bowel resections increased from 10.8% in 1998 to 29.1% in 2020. In the multivariable models stratified by elective admission, the increasing year was associated with risk of resection for obstructive indication regardless of urgency (nonelective model: odds ratio, 1.01; 95% CI, 1.00-1.02; elective model: odds ratio, 1.06; 95% CI, 1.04-1.08). CONCLUSIONS In the era of biologics, our findings demonstrate a decreasing annual rate of CD-related bowel resections but an increase in resection for obstructive indication. Our findings highlight the effect of medical therapy on surgical rates overall but suggest limited impact of current medical therapy on need of resection for stricturing disease.
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Affiliation(s)
- Kush Fansiwala
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Ellen J Spartz
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Andrew R Roney
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Mary R Kwaan
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Jenny S Sauk
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Po-Hung Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Berkeley N Limketkai
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
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Kruis W, Bokemeyer B, Jessen P, Hoesl M, Mroß M, Morgenstern J, Reimers B, Müller-Grage N, Leifeld L. Prospective Evaluation of the Prediction Score for a Mild Course of Crohn's Disease (PreMiCC) in Newly Diagnosed Patients With Crohn's Disease: The PROGNOS Study. Inflamm Bowel Dis 2025; 31:677-685. [PMID: 38648264 PMCID: PMC11879216 DOI: 10.1093/ibd/izae086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Indexed: 04/25/2024]
Abstract
BACKGROUND AND AIMS The course of Crohn's disease (CD) is highly variable. The Prospektive Evaluation eines Score zur Vorhersage eines milden Verlaufsbei neu diagnostizierten Morbus Crohn-Patienten in gastroenterologischen Fachpraxen (PROGNOS) study aimed to determine the frequency of a mild disease course and validate a proposed prediction score. METHODS The PROGNOS study is a prospective study of CD patients who were newly diagnosed and, except for 1 course of 5-aminosalicylic acid or steroids for ≤10 days, therapy-naïve. Among other predefined inclusion criteria, the initial diagnosis had to be made ≤6 weeks before enrollment. All inception cohort patients were diagnosed and screened consecutively in participating gastroenterology practices in Germany specialized in inflammatory bowel disease. All screened CD patients were scored and, if possible, included in the study for up to 5 years (NCT02193048). RESULTS A total of 201 CD patients were included in the study (43.3% male; mean age 33 years, mean follow-up 38 months). Altogether, 29.5% of the patients had a mild course at 36 months. Among those with a score ≤2, therapy escalation at 36 months was necessary for only 24.2%, whereas in the group with a score >2, therapy escalation was necessary for 70.2% of patients. In the Kaplan-Meier curve showing time to therapy escalation in the 2 groups, there was a pronounced and statistically significant divergence of the curves starting at 3 months and extending to 48 months (P < .001). CONCLUSIONS In this prospective study, about 30% of incident CD patients had a mild disease course. Our suggested PreMiCC (prediction score for a mild course of Crohn's disease) successfully predicted this.
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Affiliation(s)
- Wolfgang Kruis
- Internal Medicine, Protestant Hospital, Cologne, Germany
| | - Bernd Bokemeyer
- Department of Internal Medicine, Interdisciplinary Crohn Colitis Centre, Minden, Germany
- Clinic of General Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Petra Jessen
- Gastroenterology Practice, Kiel-Altenholz, Germany
| | - Mark Hoesl
- Gastroenterology Practice Clinic, Nuremberg, Germany
| | | | | | - Birgitta Reimers
- Department of Internal Medicine, Ferring Arzneimittel GmbH, Kiel, Germany
| | - Nike Müller-Grage
- Department of Internal Medicine, Ferring Arzneimittel GmbH, Kiel, Germany
| | - Ludger Leifeld
- Department of Internal Medicine, St. Bernward Hospital, Hildesheim, Germany
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Chen YJ, Tai CS, Chang KC, Chen HL, Ni YH, Wu JF. Early predictors of intestinal complications in pediatric-onset Crohn's disease: A long-term cohort study in Taiwan. J Formos Med Assoc 2024:S0929-6646(24)00297-3. [PMID: 38937194 DOI: 10.1016/j.jfma.2024.06.021] [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: 05/07/2024] [Revised: 06/18/2024] [Accepted: 06/20/2024] [Indexed: 06/29/2024] Open
Abstract
PURPOSE Identifying reliable prognostic factors for pediatric-onset Crohn's disease (CD) is important for guiding early treatment. This study aimed to evaluate the validity of various clinical parameters for predicting long-term intestinal complications in pediatric-onset CD patients with CD in Taiwan. METHODS This was a single-center, retrospective study. Patients diagnosed with CD under 18 years of age at our hospital between January 1999 and December 2021 were enrolled. The baseline clinical variables and the Pediatric Crohn's Disease Activity Index (PCDAI) were obtained. Patients were categorized into low-, medium-, or high-risk groups based on the 2020 European Crohn's and Colitis Organization and European Society for Pediatric Gastroenterology Hepatology and Nutrition (ECCO-ESPGHAN) guidelines. The primary endpoint was the occurrence of new intestinal complications. RESULTS Among 53 enrolled patients (33 males and 20 females), 8 patients (33.96%) developed intestinal complications during the follow-up period (median 6.42 years, 3.17-9.75 years). Patients in the initial ECCO-ESPGHAN medium- or high-risk group had a 4.71-fold higher risk of intestinal complications than those in the low-risk group [hazard ratio = 4.71, p = 0.023] after adjusting for PCDAI in the multivariate Cox proportional hazard analysis. The other clinical variables did not reach statistical significance in predicting intestinal complications. The positive and negative predictive values of the ECCO-ESPGHAN stratification method for intestinal complications were 48.15% and 80.77%, respectively. CONCLUSIONS ECCO-ESPGHAN risk stratification is an effective early predictor of long-term intestinal complications in the Taiwanese population and may be used in clinical practice to guide early advanced therapy.
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Affiliation(s)
- Yuh-Jue Chen
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Department of Pediatrics, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
| | - Chi-Shan Tai
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Kai-Chi Chang
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Huey-Ling Chen
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yen-Hsuan Ni
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Jia-Feng Wu
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; College of Medicine, National Taiwan University, Taipei, Taiwan.
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Lujan R, Buchuk R, Focht G, Yogev D, Greenfeld S, Ben-Tov A, Weisband YL, Lederman N, Matz E, Ben Horin S, Dotan I, Nevo D, Turner D. Early Initiation of Biologics and Disease Outcomes in Adults and Children With Inflammatory Bowel Diseases: Results From the Epidemiology Group of the Nationwide Israeli Inflammatory Bowel Disease Research Nucleus Cohort. Gastroenterology 2024; 166:815-825.e22. [PMID: 38331205 DOI: 10.1053/j.gastro.2024.01.041] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 01/16/2024] [Accepted: 01/26/2024] [Indexed: 02/10/2024]
Abstract
BACKGROUND & AIMS In this nationwide study, we explored whether early initiation of biologics is associated with improved outcomes in children and adults with Crohn's disease (CD) and ulcerative colitis (UC). METHODS All patients diagnosed with CD or UC in Israel (2005-2020) were included in the Epidemiology Group of the Israeli Inflammatory Bowel Disease Research Nucleus cohort, encompassing 98% of the population. We compared disease duration at biologics initiation (ie, 0-3 months, >3-12 months, >1-2 years, and >2-3 years) using the cloning, censoring, and weighting by inverse probabilities method to emulate a target trial, adjusting for time-varying confounders and selection bias. RESULTS Of the 34,375 included patients (of whom 5240 [15%] were children), 7452 of 19,264 (39%) with CD and 2235 of 15,111 (15%) with UC received biologics. In CD, by 10 years postdiagnosis, the probability of CD-related surgery decreased gradually but modestly with earlier initiation of biologics; a significant difference was noted between >2-3 years (31%) and 0-3 months (18%; P = .02; number needed to treat, 7.7), whereas there was no difference between the 0-3-month and >3-12-month periods. The 10-year probability of steroid dependency for the 0-3-month period (19%) differed both from the >2-3-year (31%; P < .001) and 1-2-year periods (37%; P < .001). In UC, no significant differences in colectomy or steroid dependency rates were observed between the treatment initiation periods. Similar trends were noted in the pediatric population. CONCLUSIONS Very early initiation of biologics was not associated with some outcomes except for a modest risk reduction of surgery and steroid dependency for CD, which requires confirmation in future studies. In UC, early introduction of biologics was not associated with reduced risk of colectomy or steroid dependency.
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Affiliation(s)
- Rona Lujan
- Juliet Keidan Institute of Pediatric Gastroenterology, Hepatology, and Nutrition, The Eisenberg R&D Authority, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Israel
| | - Rachel Buchuk
- Juliet Keidan Institute of Pediatric Gastroenterology, Hepatology, and Nutrition, The Eisenberg R&D Authority, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Israel
| | - Gili Focht
- Juliet Keidan Institute of Pediatric Gastroenterology, Hepatology, and Nutrition, The Eisenberg R&D Authority, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Israel
| | - Dotan Yogev
- Juliet Keidan Institute of Pediatric Gastroenterology, Hepatology, and Nutrition, The Eisenberg R&D Authority, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Israel
| | - Shira Greenfeld
- Kahn Sagol Maccabi Research and Innovation Center, Maccabi Health Services, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel
| | - Amir Ben-Tov
- Kahn Sagol Maccabi Research and Innovation Center, Maccabi Health Services, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel
| | | | - Natan Lederman
- Meuhedet Health Insurance Fund, Medical Division, Tel Aviv, Israel
| | - Eran Matz
- Leumit Health Services, Tel Aviv, Israel
| | - Shomron Ben Horin
- Department of Statistics and Operations Research, Tel Aviv University, Israel
| | - Iris Dotan
- Sackler Faculty of Medicine, Tel Aviv University, Israel; Sheba Medical Center, Ramat Gan, Israel
| | - Daniel Nevo
- Sackler Faculty of Medicine, Tel Aviv University, Israel; Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
| | - Dan Turner
- Juliet Keidan Institute of Pediatric Gastroenterology, Hepatology, and Nutrition, The Eisenberg R&D Authority, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Israel.
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Noor NM, Lee JC, Bond S, Dowling F, Brezina B, Patel KV, Ahmad T, Banim PJ, Berrill JW, Cooney R, De La Revilla Negro J, de Silva S, Din S, Durai D, Gordon JN, Irving PM, Johnson M, Kent AJ, Kok KB, Moran GW, Mowat C, Patel P, Probert CS, Raine T, Saich R, Seward A, Sharpstone D, Smith MA, Subramanian S, Upponi SS, Wiles A, Williams HRT, van den Brink GR, Vermeire S, Jairath V, D'Haens GR, McKinney EF, Lyons PA, Lindsay JO, Kennedy NA, Smith KGC, Parkes M. A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn's disease (PROFILE): a multicentre, open-label randomised controlled trial. Lancet Gastroenterol Hepatol 2024; 9:415-427. [PMID: 38402895 PMCID: PMC11001594 DOI: 10.1016/s2468-1253(24)00034-7] [Citation(s) in RCA: 80] [Impact Index Per Article: 80.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 01/31/2024] [Accepted: 01/31/2024] [Indexed: 02/27/2024]
Abstract
BACKGROUND Management strategies and clinical outcomes vary substantially in patients newly diagnosed with Crohn's disease. We evaluated the use of a putative prognostic biomarker to guide therapy by assessing outcomes in patients randomised to either top-down (ie, early combined immunosuppression with infliximab and immunomodulator) or accelerated step-up (conventional) treatment strategies. METHODS PROFILE (PRedicting Outcomes For Crohn's disease using a moLecular biomarker) was a multicentre, open-label, biomarker-stratified, randomised controlled trial that enrolled adults with newly diagnosed active Crohn's disease (Harvey-Bradshaw Index ≥7, either elevated C-reactive protein or faecal calprotectin or both, and endoscopic evidence of active inflammation). Potential participants had blood drawn to be tested for a prognostic biomarker derived from T-cell transcriptional signatures (PredictSURE-IBD assay). Following testing, patients were randomly assigned, via a secure online platform, to top-down or accelerated step-up treatment stratified by biomarker subgroup (IBDhi or IBDlo), endoscopic inflammation (mild, moderate, or severe), and extent (colonic or other). Blinding to biomarker status was maintained throughout the trial. The primary endpoint was sustained steroid-free and surgery-free remission to week 48. Remission was defined by a composite of symptoms and inflammatory markers at all visits. Flare required active symptoms (HBI ≥5) plus raised inflammatory markers (CRP >upper limit of normal or faecal calprotectin ≥200 μg/g, or both), while remission was the converse-ie, quiescent symptoms (HBI <5) or resolved inflammatory markers (both CRP ≤ the upper limit of normal and calprotectin <200 μg/g) or both. Analyses were done in the full analysis (intention-to-treat) population. The trial has completed and is registered (ISRCTN11808228). FINDINGS Between Dec 29, 2017, and Jan 5, 2022, 386 patients (mean age 33·6 years [SD 13·2]; 179 [46%] female, 207 [54%] male) were randomised: 193 to the top-down group and 193 to the accelerated step-up group. Median time from diagnosis to trial enrolment was 12 days (range 0-191). Primary outcome data were available for 379 participants (189 in the top-down group; 190 in the accelerated step-up group). There was no biomarker-treatment interaction effect (absolute difference 1 percentage points, 95% CI -15 to 15; p=0·944). Sustained steroid-free and surgery-free remission was significantly more frequent in the top-down group than in the accelerated step-up group (149 [79%] of 189 patients vs 29 [15%] of 190 patients, absolute difference 64 percentage points, 95% CI 57 to 72; p<0·0001). There were fewer adverse events (including disease flares) and serious adverse events in the top-down group than in the accelerated step-up group (adverse events: 168 vs 315; serious adverse events: 15 vs 42), with fewer complications requiring abdominal surgery (one vs ten) and no difference in serious infections (three vs eight). INTERPRETATION Top-down treatment with combination infliximab plus immunomodulator achieved substantially better outcomes at 1 year than accelerated step-up treatment. The biomarker did not show clinical utility. Top-down treatment should be considered standard of care for patients with newly diagnosed active Crohn's disease. FUNDING Wellcome and PredictImmune Ltd.
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Affiliation(s)
- Nurulamin M Noor
- Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, UK
| | - James C Lee
- Genetic Mechanisms of Disease Laboratory, The Francis Crick Institute, London, UK; Department of Gastroenterology, UCL Institute of Liver and Digestive Diseases, Royal Free Hospital, London, UK
| | - Simon Bond
- Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; Medical Research Council Biostatistics Unit, University of Cambridge, Cambridge, UK
| | - Francis Dowling
- Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Biljana Brezina
- Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Kamal V Patel
- Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK
| | - Tariq Ahmad
- Department of Gastroenterology, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK; Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK
| | - Paul J Banim
- Department of Gastroenterology, James Paget University Hospital, Great Yarmouth, UK
| | - James W Berrill
- Department of Gastroenterology, Royal Glamorgan Hospital, Llantrisant, UK
| | - Rachel Cooney
- GI Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Juan De La Revilla Negro
- Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Shanika de Silva
- Department of Gastroenterology, The Dudley Group NHS Foundation Trust, Dudley, UK
| | - Shahida Din
- Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK
| | - Dharmaraj Durai
- Department of Gastroenterology, Cardiff and Vale University Health Board, University Hospital of Wales, Cardiff, UK
| | - John N Gordon
- Department of Gastroenterology, Royal Hampshire County Hospital, Winchester, UK
| | - Peter M Irving
- Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Matthew Johnson
- Gastroenterology Department, Luton and Dunstable University Hospital, Luton, UK
| | - Alexandra J Kent
- Department of Gastroenterology, King's College Hospital NHS Foundation Trust, London, UK
| | - Klaartje B Kok
- Department of Gastroenterology, Royal London Hospital, Barts Health NHS Trust, London, UK
| | - Gordon W Moran
- National Institute of Health Research Nottingham Biomedical Research Centre, University of Nottingham and Nottingham University Hospitals, Nottingham, UK
| | - Craig Mowat
- Department of Gastroenterology, Ninewells Hospital, Dundee, Scotland, UK
| | - Pritash Patel
- Department of Gastroenterology, Epsom and St Helier University Hospitals, Carshalton, UK
| | - Chris S Probert
- Department of Gastroenterology, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK; Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Tim Raine
- Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Rebecca Saich
- Department of Gastroenterology, Basingstoke and North Hampshire Hospital, Basingstoke, UK
| | - Abigail Seward
- Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK
| | - Dan Sharpstone
- Department of Gastroenterology, West Suffolk NHS Foundation Trust, Bury St Edmunds, UK
| | - Melissa A Smith
- Department of Gastroenterology, University Hospitals Sussex NHS Foundation Trust, Brighton, UK
| | - Sreedhar Subramanian
- Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Sara S Upponi
- Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Alan Wiles
- Department of Gastroenterology, The Queen Elizabeth Hospital King's Lynn NHS Trust, King's Lynn, UK
| | - Horace R T Williams
- Department of Gastroenterology, Imperial College Healthcare NHS Trust, St Mary's Hospital, London, UK
| | | | - Séverine Vermeire
- Department of Gastroenterology and Hepatology, Department of Chronic Diseases and Metabolism, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - Vipul Jairath
- Division of Gastroenterology, Department of Medicine, Western University, London, Ontario, Canada
| | - Geert R D'Haens
- Department of Gastroenterology, Amsterdam University Medical Center, Amsterdam, Netherlands
| | - Eoin F McKinney
- Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, UK; PredictImmune Ltd, Babraham Research Campus, Cambridge, UK; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge, UK
| | - Paul A Lyons
- Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, UK; PredictImmune Ltd, Babraham Research Campus, Cambridge, UK; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge, UK
| | - James O Lindsay
- Department of Gastroenterology, Royal London Hospital, Barts Health NHS Trust, London, UK
| | - Nicholas A Kennedy
- Department of Gastroenterology, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK; Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK
| | - Kenneth G C Smith
- Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, UK; PredictImmune Ltd, Babraham Research Campus, Cambridge, UK; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge, UK
| | - Miles Parkes
- Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, UK.
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7
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Ranjan MK, Kumar P, Vuyyuru SK, Kante B, Mundhra SK, Golla R, Virmani S, Sharma R, Sahni P, Das P, Kalaivani M, Upadhyay AD, Makharia G, Kedia S, Ahuja V. Thiopurines Have Sustained Long-term Effectiveness in Patients with Inflammatory Bowel Disease, Which is Independent of Disease Duration at Initiation: A Propensity Score Matched Analysis. J Crohns Colitis 2024; 18:192-203. [PMID: 37584328 DOI: 10.1093/ecco-jcc/jjad135] [Citation(s) in RCA: 2] [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: 05/21/2023] [Indexed: 08/17/2023]
Abstract
BACKGROUND AND AIMS Thiopurines are viable option for the treatment of inflammatory bowel disease [IBD] in resource-limited countries. However, data on the effect of disease duration at thiopurines initiation on long-term effectiveness are limited. METHOD We performed a propensity matched analysis of a retrospective cohort of patients with ulcerative colitis [UC] and Crohn's disease [CD]. Patients initiated on thiopurines early in the disease course [≤2 years] were compared with those started late [>2 years]. Effectiveness was defined as no requirement for hospitalisation, anti-tumour necrosis factor [TNF] agents, or surgery, and minimum steroid requirement [≤1 steroid course in 2 years] during follow-up. RESULTS A total of 988 [UC: 720, CD: 268] patients were included (male: 665 [60.8%], median age: 40 [32-51] years, median follow-up: 40 [19-81] months). Overall effectiveness at 5 and 10 years was 79% and 72% in UC, and 69% and 63% in CD, respectively. After propensity score matching, there was no difference in 5- and 10-year effectiveness between early and late thiopurine initiation groups either for UC [81% and 80% vs 82% and 74%; p = 0.92] or CD [76% and 66% vs 72% and 51%, p = 0.32]. Male sex for UC (negative: hazard ratio [HR]: 0.67, 95% confidence interval [CI): 0.45-0.97; p = 0.03), and ileal involvement [positive: HR: 3.03, 95% CI: 1.32-6.71; p = 0.008], steroid-dependent disease [positive: HR: 2.70, 95% CI: 1.26-5.68; p = 0.01] and adverse events [negative: HR: 0.47, 95% CI:0.27-0.80; p = 0.005] for CD were predictors of thiopurine effectiveness. CONCLUSION Thiopurines have sustained long-term effectiveness in both UC and CD. However, early thiopurine initiation had no better effect on long-term disease outcome compared with late initiation.
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Affiliation(s)
- Mukesh Kumar Ranjan
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Peeyush Kumar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Sudheer Kumar Vuyyuru
- Department of Gastroenterology and Human Nutrition, 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
| | - Sandeep K Mundhra
- 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
| | - Raju Sharma
- Department of Radio Diagnosis, All India Institute of Medical Sciences, New Delhi, India
| | - Peush Sahni
- Department of Gastrointestinal Surgery, All India Institute of Medical Sciences, New Delhi, India
| | - Prasenjit Das
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Mani Kalaivani
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India
| | - Ashish Datt Upadhyay
- Department of Biostatistics, 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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8
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Tang WJ, Shi P, Xia HJ, Wu J, Wang YH, Huang Y. Efficacy of exclusive enteral nutrition on the mucosal healing of different gastrointestinal segments in children with Crohn's disease. J Dig Dis 2024; 25:123-132. [PMID: 38556364 DOI: 10.1111/1751-2980.13260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 02/23/2024] [Accepted: 02/26/2024] [Indexed: 04/02/2024]
Abstract
OBJECTIVE To investigate the association between disease location and segmental mucosal healing (SMH) following exclusive enteral nutrition (EEN) in children with Crohn's disease (CD). METHODS Treatment-naive pediatric patients with endoscopically active CD treated with EEN alone as induction therapy were retrospectively enrolled from January 1, 2017 to June 30, 2022. The simple endoscopic score for CD (SES-CD) was employed to score disease activity in the upper gastrointestinal (GI) tract (esophagus, stomach, duodenum), rectum, left colon, transverse colon, right colon, and terminal ileum. While the Lewis score assessed that of the small bowel from the jejunum to the proximal ileum (except the terminal ileum). The variation in the total scores for each segment and SES-CD subscores for each ileocolonic segment from baseline to 1 year after EEN therapy and the segmental endoscopic outcomes and potential predictors associated with SMH for the segments scored by SES-CD were evaluated. RESULTS Overall, 82 children with CD were enrolled. Except for the upper GI segment, scores in other segments declined significantly from baseline to EEN completion (all P < 0.001). We analyzed 486 segments (79, 80, 81, 82, 82 and 82 from upper GI tract, terminal ileum, right colon, transverse colon, left colon, and rectum) and found that the segmental SES-CD at baseline (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.55-0.70, P < 0.001) and upper GI location (OR 0.25, 95% CI 0.11-0.55, P = 0.001) were associated with SMH at EEN completion. CONCLUSION Disease location of the upper GI segment in pediatric CD was associated with SMH following EEN therapy.
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Affiliation(s)
- Wen Juan Tang
- Department of Gastroenterology, Pediatric Inflammatory Bowel Disease Research Center, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Peng Shi
- Department of Medical Statistics, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Hai Jiao Xia
- Department of Gastroenterology, Pediatric Inflammatory Bowel Disease Research Center, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Jie Wu
- Department of Gastroenterology, Pediatric Inflammatory Bowel Disease Research Center, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Yu Huan Wang
- Department of Gastroenterology, Pediatric Inflammatory Bowel Disease Research Center, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Ying Huang
- Department of Gastroenterology, Pediatric Inflammatory Bowel Disease Research Center, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
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9
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Burisch J, Safroneeva E, Laoun R, Ma C. Lack of Benefit for Early Escalation to Advanced Therapies in Ulcerative Colitis: Critical Appraisal of Current Evidence. J Crohns Colitis 2023; 17:2002-2011. [PMID: 37345930 PMCID: PMC10798867 DOI: 10.1093/ecco-jcc/jjad106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Indexed: 06/23/2023]
Abstract
Although ulcerative colitis [UC] shares many common pathways and therapeutic options with Crohn's disease [CD], CD patients are four times more likely to undergo surgery 10 years into their disease in the biological era and are more likely to have extraintestinal manifestations than UC patients. Early treatment in CD has been demonstrated to modify the natural history of the disease and potentially delay surgery. Previous reviews on this topic have borrowed their evidence from CD to make UC-specific recommendations. This review highlights the emergence of UC-specific data from larger cohort studies and a comprehensive individual patient data systemic review and meta-analysis to critically appraise evidence on the utility of early escalation to advanced therapies with respect to short-, medium-, and long-term outcomes. In UC, the utility of the early escalation concept for the purposes of changing the natural history, including reducing colectomy and hospitalizations, is not supported by the available data. Data on targeting clinical, biochemical, endoscopic, and histological outcomes are needed to demonstrate that they are meaningful with regard to achieving reductions in hospitalization and surgery, improving quality of life, and minimizing disability. Analyses of different populations of UC patients, such as those with 'relapsing & remitting' disease or with severe or complicated disease course, are urgently needed. The costs and risk/benefit profile of some of the newer advanced therapies should be carefully considered. In this clinical landscape, it appears premature to advocate an indiscriminate 'one size fits all' approach to escalating to advanced therapies early during the course of UC.
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Affiliation(s)
- Johan Burisch
- Gastro Unit, Medical Division, Copenhagen University Hospital – Amager and Hvidovre, Hvidovre, Denmark
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Copenhagen University Hospital – Amager and Hvidovre, Hvidovre, Denmark
| | - Ekaterina Safroneeva
- Tillotts Pharma AG, Rheinfelden, Switzerland
- Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
| | | | - Christopher Ma
- Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada
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10
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Meijer LL, Ayez N, van Kessel CS. Crohn's disease: preserve or resect the mesentery? Br J Surg 2023; 110:1415-1418. [PMID: 37178332 DOI: 10.1093/bjs/znad135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 04/11/2023] [Accepted: 04/20/2023] [Indexed: 05/15/2023]
Affiliation(s)
| | - Ninos Ayez
- Department of Surgery, Amphia, Breda, The Netherlands
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11
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Aghlara-Fotovat S, Musteata E, Doerfert MD, Baruch M, Levitan M, Tabor JJ, Veiseh O. Hydrogel-encapsulation to enhance bacterial diagnosis of colon inflammation. Biomaterials 2023; 301:122246. [PMID: 37481834 PMCID: PMC10792543 DOI: 10.1016/j.biomaterials.2023.122246] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Revised: 06/13/2023] [Accepted: 07/12/2023] [Indexed: 07/25/2023]
Abstract
Bacteria can be genetically programmed to sense and report the presence of disease biomarkers in the gastrointestinal (GI) tract. However, diagnostic bacteria are typically delivered via oral administration of liquid cultures, resulting in poor survival and high dispersal in vivo. These limitations confound recovery and analysis of engineered bacteria from GI or stool samples. Here, we demonstrate that encapsulating bacteria inside of alginate core-shell particles enables robust survival, containment, and diagnostic function in vivo. We demonstrate these benefits by encapsulating a strain engineered to report the presence of the biomarker thiosulfate via fluorescent protein expression in order to diagnose dextran sodium sulfate-induced colitis in rats. Hydrogel-encapsulated bacteria engineered to sense and respond to physiological stimuli should enable minimally invasive monitoring of a wide range of diseases and have applications as next-generation smart therapeutics.
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Affiliation(s)
| | - Elena Musteata
- Systems Synthetic and Physical Biology, Rice University, Houston, TX, USA
| | | | - Moshe Baruch
- Department of Bioengineering, Rice University, Houston, TX, USA
| | - Maya Levitan
- Department of Bioengineering, Rice University, Houston, TX, USA
| | - Jeffrey J Tabor
- Department of Bioengineering, Rice University, Houston, TX, USA; Systems Synthetic and Physical Biology, Rice University, Houston, TX, USA; Department of Biosciences, Rice University, Houston, TX, USA.
| | - Omid Veiseh
- Department of Bioengineering, Rice University, Houston, TX, USA.
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12
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Dignass A, Rath S, Kleindienst T, Stallmach A. Review article: Translating STRIDE-II into clinical reality - Opportunities and challenges. Aliment Pharmacol Ther 2023; 58:492-502. [PMID: 37382397 DOI: 10.1111/apt.17622] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 01/04/2023] [Accepted: 06/07/2023] [Indexed: 06/30/2023]
Abstract
BACKGROUND With the introduction of novel therapies for inflammatory bowel diseases (IBD), 'treat-to-target' strategies are increasingly discussed to improve short- and long-term outcomes in patients with IBD. AIM To discuss opportunities and challenges of a treat-to-target approach in light of the current 'Selecting Therapeutic Targets in Inflammatory Bowel Disease' (STRIDE-II) consensus METHODS: The 2021 update of STRIDE-II encompasses 13 evidence- and consensus-based recommendations for treat-to-target strategies in adults and children with IBD. We highlight the potential implications and limitations of these recommendations for clinical practice. RESULTS STRIDE-II provides valuable guidance for personalised IBD management. It reflects scientific progress as well as increased evidence of improved outcomes when more ambitious treatment goals such as mucosal healing are achieved. CONCLUSIONS Prospective studies, objective criteria for risk stratification, and better predictors of therapeutic response are needed to potentially render 'treating to target' more effective in the future.
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Affiliation(s)
- Axel Dignass
- Department of Medicine I, Agaplesion Markus Hospital, Frankfurt/Main, Germany
| | - Stefan Rath
- Department of Medical Immunology, AbbVie Deutschland GmbH & Co. KG, Wiesbaden, Germany
| | - Thomas Kleindienst
- Department of Medical Immunology, AbbVie Deutschland GmbH & Co. KG, Wiesbaden, Germany
| | - Andreas Stallmach
- Department of Internal Medicine IV, University Hospital Jena, Jena, Germany
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13
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Tavares de Sousa H, Magro F. How to Evaluate Fibrosis in IBD? Diagnostics (Basel) 2023; 13:2188. [PMID: 37443582 DOI: 10.3390/diagnostics13132188] [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: 05/25/2023] [Revised: 06/21/2023] [Accepted: 06/25/2023] [Indexed: 07/15/2023] Open
Abstract
In this review, we will describe the importance of fibrosis in inflammatory bowel disease (IBD) by discussing its distinct impact on Crohn's disease (CD) and ulcerative colitis (UC) through their translation to histopathology. We will address the existing knowledge on the correlation between inflammation and fibrosis and the still not fully explained inflammation-independent fibrogenesis. Finally, we will compile and discuss the recent advances in the noninvasive assessment of intestinal fibrosis, including imaging and biomarkers. Based on the available data, none of the available cross-sectional imaging (CSI) techniques has proved to be capable of measuring CD fibrosis accurately, with MRE showing the most promising performance along with elastography. Very recent research with radiomics showed encouraging results, but further validation with reliable radiomic biomarkers is warranted. Despite the interesting results with micro-RNAs, further advances on the topic of fibrosis biomarkers depend on the development of robust clinical trials based on solid and validated endpoints. We conclude that it seems very likely that radiomics and AI will participate in the future non-invasive fibrosis assessment by CSI techniques in IBD. However, as of today, surgical pathology remains the gold standard for the diagnosis and quantification of intestinal fibrosis in IBD.
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Affiliation(s)
- Helena Tavares de Sousa
- Gastroenterology Department, Algarve University Hospital Center, 8500-338 Portimão, Portugal
- ABC-Algarve Biomedical Center, University of Algarve, 8005-139 Faro, Portugal
| | - Fernando Magro
- Unit of Pharmacology and Therapeutics, Department of Biomedicine, Faculty of Medicine, University of Porto, 4200-450 Porto, Portugal
- Department of Gastroenterology, São João University Hospital Center, 4200-319 Porto, Portugal
- CINTESIS@RISE, Faculty of Medicine, University of Porto, 4200-450 Porto, Portugal
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14
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Rodríguez-Lago I, Blackwell J, Mateos B, Marigorta UM, Barreiro-de Acosta M, Pollok R. Recent Advances and Potential Multi-Omics Approaches in the Early Phases of Inflammatory Bowel Disease. J Clin Med 2023; 12:jcm12103418. [PMID: 37240524 DOI: 10.3390/jcm12103418] [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: 03/20/2023] [Revised: 05/01/2023] [Accepted: 05/09/2023] [Indexed: 05/28/2023] Open
Abstract
Inflammatory bowel disease leads to debilitating gastrointestinal symptoms and reduced quality of life, resulting in a significant burden on healthcare utilization and costs. Despite substantial advancements in diagnosis and treatment, there may still be considerable delays in diagnosing some patients. To reduce disease progression before the full disease spectrum appears and improve prognostic outcomes, several strategies have concentrated on early intervention and prevention. Recent evidence shows that initial immune response changes and endoscopic lesions may exist for years before diagnosis, implying the existence of a preclinical phase of inflammatory bowel disease comparable to findings in other immune-mediated disorders. In this review, we highlight the most relevant findings regarding preclinical inflammatory bowel disease and the prospective role of novel omics techniques in this field.
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Affiliation(s)
- Iago Rodríguez-Lago
- Gastroenterology Department, Hospital Universitario de Galdakao, 48960 Galdakao, Spain
- Biocruces Bizkaia Health Research Institute, 48960 Galdakao, Spain
- Deusto University, 48007 Bilbao, Spain
| | | | - Beatriz Mateos
- Integrative Genomics Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain
| | - Urko M Marigorta
- Integrative Genomics Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain
- IKERBASQUE, Basque Foundation for Sciences, 48009 Bilbao, Spain
| | - Manuel Barreiro-de Acosta
- Gastroenterology Department, Hospital Clínico Universitario de Santiago, 15706 Santiago de Compostela, Spain
| | - Richard Pollok
- Gastroenterology Department, St George's University of London, London SW17 0RE, UK
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15
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Le Berre C, Danese S, Peyrin-Biroulet L. Can we change the natural course of inflammatory bowel disease? Therap Adv Gastroenterol 2023; 16:17562848231163118. [PMID: 37153497 PMCID: PMC10159495 DOI: 10.1177/17562848231163118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Accepted: 02/01/2023] [Indexed: 05/09/2023] Open
Abstract
Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are lifelong diseases characterized by chronic inflammation of the gastrointestinal tract leading to its progressive and irreversible destruction. Whether early initiation of IBD-specific therapy impacts the long-term course of the disease remains unclear and has to be further explored in prospective disease-modification trials. Historically, surgery and hospitalization rates have been the surrogate markers to measure disease progression in IBD, providing an overview of the effectiveness of medical therapies. However, neither surgery nor hospitalization necessarily reflects a fail in therapeutic medical management, and many confounding factors make them biased outcomes. The Selecting Endpoints for Disease-Modification Trials consensus has defined the disease-modification endpoints required for these trials, including the impact of the disease on patient's life (health-related quality of life, disability, and fecal incontinence), the mid-term disease complications (bowel damage in CD, IBD-related surgery and hospitalizations, disease extension in UC, extra-intestinal manifestations, permanent stoma, short bowel syndrome), and the development of dysplasia/cancer and mortality in the long term. Most available data in the literature regarding the impact of current therapies on disease progression focused on anti-tumor necrosis factor agents and are based on retrospective or post-hoc studies. Thus, prospective disease-modification trials are pressingly required to explore the effectiveness of early intensified treatment in patients with severe disease or at risk for disease progression.
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Affiliation(s)
| | - Silvio Danese
- Department of Gastroenterology and Digestive
Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele
University, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE
U1256, University Hospital of Nancy, University of Lorraine,
Vandoeuvre-lès-Nancy, France
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16
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Estevinho MM, Leão Moreira P, Silva I, Laranjeira Correia J, Santiago M, Magro F. A scoping review on early inflammatory bowel disease: definitions, pathogenesis, and impact on clinical outcomes. Therap Adv Gastroenterol 2022; 15:17562848221142673. [PMID: 36569381 PMCID: PMC9772959 DOI: 10.1177/17562848221142673] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Accepted: 11/15/2022] [Indexed: 12/23/2022] Open
Abstract
Background Crohn's disease (CD) and ulcerative colitis (UC) arise from a dysregulation of the balance between commensal microbiota and mucosal-associated immune system, in patients with genetic and environmental predisposition. Different pathophysiological mechanisms have been reported to influence disease history, with impact on disease phenotype and risk of complications. Objectives This review aims to summarize the definitions of early CD and UC, analyze the underlying immunological mechanisms, and evaluate the impact of recognizing and treating early inflammatory bowel disease (IBD) on patients' prognosis (short- and long-term outcomes). Design To address this issue, we have performed a scoping review. Data sources and methods Three online databases (MEDLINE, Web of Science, and ScienceDirect) were searched and the results were independently screened by two reviewers. Results From 683 records identified, 42 manuscripts evaluating early IBD in adult patients were included. The 'early CD' concept was first described in 2008. Four years later, an international consensus proposed the definition of diagnosis up to 18 months, in patients without previous or current need for disease-modifying therapies. Several other definitions have been proposed; the '2 years since diagnosis' is the most used, regardless of disease characteristics or medication. The amount of evidence on early UC is lower and more recent. Regarding early disease pathogenesis, most theories emphasize the prominent role of innate immunity, followed by early-Th1 adaptive response. Conclusion The treatment of early CD seems to be crucial for the management of CD patients, impacting short-, medium-, and long-term outcomes. On the other hand, the early treatment of UC appears to be less advantageous, yet evidence comes from only a few retrospective studies.
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Affiliation(s)
- Maria Manuela Estevinho
- Department of Gastroenterology, Vila Nova de Gaia Espinho Hospital Center, Vila Nova de Gaia, Portugal
- Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Paula Leão Moreira
- Unidade de Farmacologia Clínica, São João Hospital University Centre, Porto, Portugal
| | - Isabel Silva
- Unidade de Farmacologia Clínica, São João Hospital University Centre, Porto, Portugal
| | - João Laranjeira Correia
- Department of Gastroenterology, Vila Nova de Gaia Espinho Hospital Center, Vila Nova de Gaia, Portugal
| | - Mafalda Santiago
- Portuguese Group of Studies in Inflammatory Bowel Disease (Grupo de Estudos da Doença Inflamatória Intestinal - GEDII), Porto, Portugal
- Center for Health Technology and Services Research (CINTESIS), Porto, Portugal
| | - Fernando Magro
- Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Rua Dr. Plácido Costa, 3, Porto 4200-450, Portugal
- Unidade de Farmacologia Clínica, São João Hospital University Centre, Porto, Portugal
- Center for Health Technology and Services Research (CINTESIS), Porto, Portugal
- Department of Gastroenterology, São João Hospital University Centre, Porto, Portugal
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17
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Targownik LE, Bernstein CN, Benchimol EI, Kaplan GG, Singh H, Tennakoon A, Nugent Z, Coward SB, Kuenzig ME, Murthy SK. Earlier Anti-TNF Initiation Leads to Long-term Lower Health Care Utilization in Crohn's Disease but Not in Ulcerative Colitis. Clin Gastroenterol Hepatol 2022; 20:2607-2618.e14. [PMID: 35247552 DOI: 10.1016/j.cgh.2022.02.021] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 02/02/2022] [Accepted: 02/03/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The timing of initiating biologic therapy in persons with Crohn's disease (CD) and ulcerative colitis (UC) is an area of ongoing controversy. In particular, there is concern that delaying the initiation of biologic therapy may lead to more treatment-resistant disease, which can result in more complications and hospitalizations. METHODS We used health administrative data from Manitoba, Canada to identify all persons with a new diagnosis of inflammatory bowel disease (IBD) between 2001 and 2018 who received tumor necrosis factor antagonists (anti-TNF) therapy and had at least 1 year of post anti-TNF initiation follow-up. We measured the rates of hospitalization, surgery, and outpatient visits, prior to and for up to 5 years following anti-TNF initiation. We compared the rates of these health care utilization outcomes between persons receiving anti-TNFs within 2 years following diagnosis and those receiving anti-TNFs more than 2 years following IBD diagnosis. We used inverse probability treatment weighting to adjust for baseline differences in risk between the 2 groups. RESULTS Among 742 persons with CD, early anti-TNF initiators had fewer IBD-specific and overall hospitalizations over the 5 years following the start of therapy. Incidence of resective surgery was also lower in earlier anti-TNF initiators with CD if the first year following initiation was excluded from the analysis. In 318 cases of UC, there was no impact of the timing of anti-TNF therapy on the rates of hospitalization and surgery. CONCLUSIONS Earlier administration of anti-TNF therapy is associated with reduced downstream health care resource utilization in CD, though these impacts are not evident in UC.
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Affiliation(s)
- Laura E Targownik
- Division of Gastroenterology and Hepatology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
| | - Charles N Bernstein
- Section of Gastroenterology, Department of Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, and University of Manitoba IBD Clinical and Research Centre, Winnipeg, Manitoba, Canada
| | - Eric I Benchimol
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children and Child Health Evaluative Sciences, SickKids Research Institute, Toronto, Ontario Canada; Department of Paediatrics and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; ICES, Toronto, Ontario, Canada
| | - Gilaad G Kaplan
- Department of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Harminder Singh
- Section of Gastroenterology, Department of Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, and University of Manitoba IBD Clinical and Research Centre, Winnipeg, Manitoba, Canada; Department of Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Aruni Tennakoon
- Section of Gastroenterology, Department of Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, and University of Manitoba IBD Clinical and Research Centre, Winnipeg, Manitoba, Canada
| | - Zoann Nugent
- Section of Gastroenterology, Department of Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, and University of Manitoba IBD Clinical and Research Centre, Winnipeg, Manitoba, Canada
| | - Stephanie B Coward
- Department of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - M Ellen Kuenzig
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children and Child Health Evaluative Sciences, SickKids Research Institute, Toronto, Ontario Canada
| | - Sanjay K Murthy
- ICES, Toronto, Ontario, Canada; The Ottawa Hospital IBD Centre, University of Ottawa and Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
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18
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Zhao M, Lirhus S, Lördal M, Langholz E, Knudsen T, Voutilainen M, Høivik ML, Moum B, Anisdahl K, Saebø B, Haiko P, Malmgren C, Coskun M, Melberg HO, Burisch J. Therapeutic management and outcomes in inflammatory bowel diseases, 2010 to 2017 in cohorts from Denmark, Sweden and Norway. Aliment Pharmacol Ther 2022; 56:989-1006. [PMID: 35902223 DOI: 10.1111/apt.17145] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 07/05/2021] [Accepted: 07/01/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND Despite the increasing use of biologics in patients with inflammatory bowel disease (IBD), real-world data about outcomes in the era of biologics remain inconclusive. AIMS To investigate trends in surgeries, hospitalisations and medication use in patients with IBD in a multinational, population-based cohort METHODS: We included 42,894 patients with ulcerative colitis (UC) and 24,864 with Crohn's disease (CD) who were diagnosed between 2010 and 2017 in Denmark, Norway and Sweden. We extracted data about surgeries, hospitalisations and medications from national registries and compared across countries and diagnosis years. RESULTS Between 2010 and 2017, 2-year surgery rates were 4-7% in UC and 10-15% in CD and were stable over time. Two-year hospitalisation rates increased in Denmark (UC: 20% to 35%; CD: 27% to 32%) but were stable in Norway and Sweden (fluctuating between 33% and 37% in UC, and 46% and 52% in CD). Two-year rates of biologic use increased in both UC (7% to 16% in Denmark, 8% to 18% in Norway) and CD (22% to 26% in Denmark; 21% to 35% in Norway). Two-year rates of immunomodulator use increased in Norway (from 14% to 23% in UC; 37% to 45% in CD) and Sweden (from 41% to 52% in CD), but were stable in Denmark (between 17% and 21% in UC; 39% to 46% in CD). CONCLUSION Between 2010 and 2017, surgery rates among Scandinavian patients with IBD remained stable, with no clear changes in hospitalisation rates despite the increasing use of immunomodulators and biologics.
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Affiliation(s)
- Mirabella Zhao
- Gastrounit, Medical Division, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark.,Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
| | - Sandre Lirhus
- Department of Health Management and Health Economics, Institute of Health and Society, University of Oslo, Oslo, Norway
| | - Mikael Lördal
- Division of Gastroenterology and Hepatology, Department of Medicine, Danderyds Hospital, Stockholm, Sweden
| | - Ebbe Langholz
- Gastro Unit, Medical Division, Herlev University Hospital, Herlev, Denmark.,Institute for Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Torben Knudsen
- Department of Medicine, Hospital of South West Denmark, Esbjerg, Denmark.,Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
| | - Markku Voutilainen
- Department of Gastroenterology, University of Turku and Turku University Hospital, Turku, Finland
| | - Marte Lie Høivik
- Department of Gastroenterology, Oslo University Hospital, Oslo, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Bjorn Moum
- Department of Gastroenterology, Oslo University Hospital, Oslo, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Karoline Anisdahl
- Department of Gastroenterology, Oslo University Hospital, Oslo, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | | | - Paula Haiko
- Takeda Oy, Medical Affairs, Helsinki, Finland
| | | | - Mehmet Coskun
- Takeda Pharma A/S, Medical Affairs, Vallensbaek Strand, Denmark
| | - Hans Olav Melberg
- Department of Health Management and Health Economics, Institute of Health and Society, University of Oslo, Oslo, Norway
| | - Johan Burisch
- Gastrounit, Medical Division, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark.,Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
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19
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Wong ECL, Dulai PS, Marshall JK, Jairath V, Reinisch W, Narula N. Comparative Efficacy of Infliximab vs Ustekinumab for Maintenance of Clinical Response in Biologic Naïve Crohn's Disease. Inflamm Bowel Dis 2022:6654444. [PMID: 35920382 DOI: 10.1093/ibd/izac168] [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: 05/17/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND There is a need to better understand the positioning of biologic therapies for long-term outcomes in biologic-naïve Crohn's disease (CD). We assessed the comparative effectiveness of infliximab and ustekinumab among induction responders for 1-year outcomes. METHODS This post hoc analysis included data from 220 biologic-naïve CD participants with response to induction therapy from 2 clinical trial programs. Participants achieving 1-year clinical remission (CR) (Crohn's disease activity index <150), corticosteroid-free CR, normalization of fecal calprotectin (FC), endoscopic response (Simple Endoscopic Score for CD decrease ≥50% from baseline), and endoscopic remission (ER) (Simple Endoscopic Score for CD <3) were compared. Multivariate logistic regression evaluated the likelihood of achieving the outcomes adjusted for confounders. Propensity score matching created a cohort with similar distribution of baseline covariates. RESULTS One-year CR and corticosteroid-free CR rates were similar between infliximab-treated and ustekinumab-treated patients (CR, 66 of 110 [60.0%] vs 63 of 110 [57.3%]; adjusted odds ratio [aOR], 1.15; 95% CI, 0.67-1.98; P = .681; corticosteroid-free CR, 11 of 28 (39.3%) vs 27 of 51 [52.9%]; aOR, 0.58; 95% CI, 0.23-1.47; P = .251). Compared with ustekinumab-treated patients, infliximab-treated participants were more likely to achieve 1-year endoscopic response (43 of 92 [46.7%] vs 6 of 30 [20.0%], aOR, 3.59; 95% CI, 1.34-9.66; P = .011) and ER (31 of 92 [33.7%] vs 4 of 30 [13.3%]; aOR, 3.35; 95% CI, 1.07-10.49; P = .038). Among patients with FC ≥250 mg/kg at baseline, normalization (<250 mg/kg) at 1-year was similar between groups. Similar results were observed within the propensity matched population for all analyses. CONCLUSIONS Treatment with infliximab and ustekinumab among induction responders achieved 1-year CR with similar efficacy, but infliximab may confer greater benefit for endoscopic outcomes. Findings should be interpreted with caution as our analyses were unpowered.
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Affiliation(s)
- Emily C L Wong
- 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
| | - Vipul Jairath
- Department of Medicine, Division of Gastroenterology, Western University, London, 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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20
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Narula N, Wong ECL, Dulai PS, Sengupta NK, Marshall JK, Colombel JF, Reinisch W. Comparative Efficacy and Rapidity of Action for Infliximab vs Ustekinumab in Biologic Naïve Crohn's Disease. Clin Gastroenterol Hepatol 2022; 20:1579-1587.e2. [PMID: 33838348 DOI: 10.1016/j.cgh.2021.04.006] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 03/30/2021] [Accepted: 04/03/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Comparative effectiveness has become increasingly important to help position therapies for inflammatory bowel disease. We compared the efficacy and rapidity of onset of action of infliximab vs ustekinumab induction therapy for moderate to severe biologic-naïve Crohn's disease (CD) using patient-level data from randomized controlled trials. METHODS This was a post hoc analysis of 2 large CD clinical trial programs that included data on 420 biologic-naïve CD patients. Differences in proportions of patients achieving week 6 clinical remission, clinical response, and normalization of calprotectin were compared. Multivariate logistic regression was used to adjust for confounders. Sensitivity analysis was conducted using propensity scores to create a cohort of matched participants with similar distribution of baseline covariates. RESULTS At week 6, a comparable number of patients achieved clinical remission with infliximab compared with patients treated with ustekinumab (44.9% vs 37.9%; adjusted odds ratio [aOR], 1.22; 95% CI, 0.79-1.89). Similarly, at week 6 the clinical response rates were not significantly different (58.4% infliximab vs 54.9% ustekinumab; aOR, 1.25; 95% CI, 0.82-1.90). No significant difference was observed between treatment groups for achieving a week 6 fecal calprotectin level less than 250 mcg/L in those with increased values at baseline (42.3% infliximab vs 34.7% ustekinumab; aOR, 1.34; 95% CI, 0.79-2.28). Similar results were seen for all analyses performed within the propensity matched cohort. CONCLUSIONS Based on this post hoc analysis, infliximab and ustekinumab appear to have similar efficacy and speed of onset in patients with CD who are biologic-naïve.
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Affiliation(s)
- Neeraj Narula
- Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
| | - Emily C L Wong
- Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Parambir S Dulai
- Division of Gastroenterology, University of California San Diego, La Jolla, California
| | - Neil K Sengupta
- Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - John K Marshall
- Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Jean-Frederic Colombel
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Walter Reinisch
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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21
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Liu F, Tang J, Ye L, Tan J, Qiu Y, Hu F, He J, Chen B, He Y, Zeng Z, Mao R, Cao Q, Gao X, Chen M. Prophylactic Antitubercular Therapy Is Associated With Accelerated Disease Progression in Patients With Crohn's Disease Receiving Anti-TNF Therapy: A Retrospective Multicenter Study. Clin Transl Gastroenterol 2022; 13:e00493. [PMID: 35758823 PMCID: PMC9236600 DOI: 10.14309/ctg.0000000000000493] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 04/05/2022] [Indexed: 11/23/2022] Open
Abstract
INTRODUCTION Prophylactic antitubercular therapy (ATT) is widely prescribed in patients with Crohn's disease (CD) receiving antitumor necrosis factor (anti-TNF) treatment. However, antitubercular agents have been demonstrated to possess profibrotic effects. We aimed to evaluate whether ATT accelerated disease progression in patients with CD receiving anti-TNF treatment. METHODS A retrospective, multicenter study was performed in CD patients presented with inflammatory behavior (B1) and treated with anti-TNF agents. Disease progression was defined as the development of a stricturing (B2) or penetrating (B3) phenotype. ATT users were propensity score-matched with non-ATT users. Survival and multivariable Cox analyses were used to identify factors associated with disease progression. RESULTS We enrolled 441 patients, including 295 ATT users and 146 non-ATT users, with a median follow-up of 3.15 years (interquartile range: 1.6-4.7). The cumulative rates of disease progression in the ATT group were constantly higher than those in the non-ATT group after 1-, 3-, 5-, and 10-year follow-ups, respectively (P = 0.031). Multivariable Cox analysis identified ATT as an independent risk factor for disease progression using both the whole (hazard ratio = 2.22; 95% confidence interval: 1.11-4.48; P = 0.025) and propensity score-matched cohorts (hazard ratio = 2.35; 95% confidence interval: 1.07-5.14; P = 0.033). In subgroup analysis, patients receiving ATT ≥4.5 months had a significantly higher rate of disease progression compared with patients receiving ATT <4.5 months (P = 0.005) and non-ATT treatment (P = 0.036). DISCUSSION Prophylactic ATT with duration over 4.5 months was associated with disease progression in patients with CD receiving anti-TNF treatment.
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Affiliation(s)
- Fen Liu
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jian Tang
- Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Lingna Ye
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jinyu Tan
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yun Qiu
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Fan Hu
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jinshen He
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Baili Chen
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yao He
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhirong Zeng
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Ren Mao
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Qian Cao
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiang Gao
- Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Minhu Chen
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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22
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Rakowsky S, Papamichael K, Cheifetz AS. Choosing the right biologic for complications of inflammatory bowel disease. Expert Rev Gastroenterol Hepatol 2022; 16:235-249. [PMID: 35094628 DOI: 10.1080/17474124.2022.2036122] [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: 03/25/2021] [Accepted: 01/27/2022] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Inflammatory bowel disease (IBD) is a chronic, inflammatory condition that involves the intestinal tract, and can also present with extra-intestinal manifestations (EIM). Choosing the right treatment for IBD is often nuanced and decisions can become even more complicated when a patient presents with or develops a complication of the disease. AREAS COVERED We aimed to provide an overview of the most common complications of IBD, specifically intestinal and EIM, and summarize the data regarding biologic therapy for treatment of these conditions. A comprehensive literature review was performed using PubMed and Medline databases to identify studies published in the English language relevant to the broad scope of this review. EXPERT OPINION There are still significant gaps in our understanding of the pathophysiology of IBD and its treatment, especially in regards to complications of the disease. As novel therapies continue to emerge for treatment of IBD, we feel concurrent examination of their impact on intestinal complications and EIM of IBD is important and should be a priority of future research.
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Affiliation(s)
- Shana Rakowsky
- Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA USA
| | - Konstantinos Papamichael
- Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA USA
| | - Adam S Cheifetz
- Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA USA
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23
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Zhao M, Sall Jensen M, Knudsen T, Kelsen J, Coskun M, Kjellberg J, Burisch J. Trends in the use of biologicals and their treatment outcomes among patients with inflammatory bowel diseases - a Danish nationwide cohort study. Aliment Pharmacol Ther 2022; 55:541-557. [PMID: 34881439 DOI: 10.1111/apt.16723] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 06/21/2021] [Accepted: 11/19/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND Therapeutic management of inflammatory bowel diseases (IBD) is rapidly evolving, with an expanding armoury of biological drugs at our disposal. However, real-world findings about treatment persistence and the impact of biologicals on surgery remain inconsistent. AIMS This study aimed to investigate trends in biological use and surgery rates in a nationwide cohort of biological-naïve IBD patients. METHODS Patients with IBD who initiated biological treatment between 2011 and 2018 were identified in the Danish National Patient Registry. Data on use of biologicals, surgeries and healthcare costs were retrieved and analysed for time trends. RESULTS Between 2011 and 2018, a total of 6,036 IBD (51% ulcerative colitis (UC), 49% Crohn's disease (CD)) patients received biological treatment for the first time. Cumulative use of biologicals increased from 5.0% to 10.8% among UC and 8.9%-14.5% among CD patients. Infliximab remained the most-prescribed first-line biological for UC and CD. Treatment persistence was 44.3% and 16.9% after 1 and 3 years in UC, compared to 59.9% and 33.6% in CD patients. Overall, 32.8% of patients switched to a second biological. Surgery rates decreased in both UC (P = 0.015) and CD (P = 0.008) patients and remained significant for UC in the Cox regression model (P = 0.002). Outpatient and surgical costs also fell among both UC and CD patients. CONCLUSIONS Persistence rates for first-line biologicals among IBD patients were low and one-third switched treatment. Surgery rates and direct costs decreased over time, but whether this is related to the use of biologicals has yet to be determined.
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Affiliation(s)
- Mirabella Zhao
- Gastro Unit, Medical Division, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.,Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidvore Hospital, University of Copenhagen, Hvidovre, Denmark
| | - Morten Sall Jensen
- VIVE - The Danish Centre for Social Science Research, Copenhagen, Denmark
| | - Torben Knudsen
- Department of Gastroenterology, Hospital of South West Denmark, Esbjerg, Denmark
| | - Jens Kelsen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N, Denmark
| | - Mehmet Coskun
- Takeda Pharma A/S, Medical Affairs, Vallensbaek Strand, Denmark
| | - Jakob Kjellberg
- VIVE - The Danish Centre for Social Science Research, Copenhagen, Denmark
| | - Johan Burisch
- Gastro Unit, Medical Division, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.,Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidvore Hospital, University of Copenhagen, Hvidovre, Denmark
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24
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Pollok RCG, Jayasooriya N. Editorial: early and persistent biological treatment and its impact on long term surgical outcomes in inflammatory bowel disease. Aliment Pharmacol Ther 2022; 55:370-371. [PMID: 35040166 DOI: 10.1111/apt.16747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Richard C G Pollok
- Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK.,Institute for Infection and Immunity, St George's University of London, London, UK
| | - Nishani Jayasooriya
- Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK.,Institute for Infection and Immunity, St George's University of London, London, UK
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25
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Bakkaloglu OK, Eskazan T, Celik S, Kurt EA, Hatemi I, Erzin Y, Celik AF. Can we predict mucosal remission in ulcerative colitis more precisely with a redefined cutoff level of C-reactive protein? Colorectal Dis 2022; 24:77-84. [PMID: 34610199 DOI: 10.1111/codi.15940] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Revised: 09/20/2021] [Accepted: 09/22/2021] [Indexed: 02/08/2023]
Abstract
AIM Most patients with ulcerative colitis (UC) with active mucosal disease have a lower C-reactive protein (CRP) level than the classic accepted cutoff level (≤5 mg/l). We aimed to predict the mucosal remission in UC with an optimal cutoff level of CRP when mucosal activity and extensiveness of UC were both considered. METHOD In this retrospective study, we evaluated CRP values and their relation to mucosal extension and UC activity in 331 colonoscopic examinations performed between December 2016 and March 2019. Endoscopic activity and disease extension were assessed using Mayo scores and the Montreal classification. RESULTS The Mayo 2 and 3 groups' CRP values were significantly higher when compared with Mayo 0-1 between values of E1 and both E2 and E3 with an increasing trend. The standard CRP cutoff level ≤5 mg/l only yielded 55% specificity in predicting mucosal remission. In the ROC analysis, a CRP cutoff level ≤2.9 mg/l predicted an overall mucosal remission (Mayo 0-1) with 77% sensitivity and 80% specificity, and ≤1.9 mg/l predicted Mayo-0 with 70% sensitivity and specificity. In the clinical remission subgroup, the overall CRP cutoff level was even lower, at ≤1.58 mg/l. CONCLUSION An overall CRP cutoff level ≤2.9 mg/l predicts mucosal remission in UC better than the standard cutoff ≤5 mg/l. Mucosal remission in stable clinical remission may present with an even lower CRP level. An increasing trend in the CRP level from E1 through E3 even in mucosal remission suggests that both histological inflammation and extensiveness may have some influence on a CRP-based prediction of endoscopic remission.
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Affiliation(s)
- Oguz Kagan Bakkaloglu
- Section of Gastroenterology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University - Cerrahpasa, Istanbul, Turkey
| | - Tugce Eskazan
- Section of Gastroenterology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University - Cerrahpasa, Istanbul, Turkey
| | - Sinem Celik
- Atasehir Acibadem Hospital, Acibadem University, Istanbul, Turkey
| | - Enes Ali Kurt
- Section of Gastroenterology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University - Cerrahpasa, Istanbul, Turkey
| | - Ibrahim Hatemi
- Section of Gastroenterology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University - Cerrahpasa, Istanbul, Turkey
| | - Yusuf Erzin
- Section of Gastroenterology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University - Cerrahpasa, Istanbul, Turkey
| | - Aykut Ferhat Celik
- Section of Gastroenterology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University - Cerrahpasa, Istanbul, Turkey
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26
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Yamamoto-Furusho JK, Parra-Holguín NN. Diagnostic Delay of Inflammatory Bowel Disease Is Significantly Higher in Public versus Private Health Care System in Mexican Patients. Inflamm Intest Dis 2021; 7:72-80. [PMID: 35979192 PMCID: PMC9294956 DOI: 10.1159/000520522] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 10/27/2021] [Indexed: 12/04/2022] Open
Abstract
Introduction Inflammatory bowel disease (IBD) includes ulcerative colitis (UC) and Crohn's disease (CD) characterized by a fluctuating course with periods of clinical activity and remission. No previous studies have demonstrated the frequency of delay at diagnosis and its associated factors in Mexico and Latin America. The aim of this study was to evaluate diagnostic delay of IBD in the last 4 decades in 2 different health care systems (public vs. private) and its associated factors. Methods This is a cohort study that included 1,056 patients with a confirmed diagnosis of IBD from public and private health care systems. The diagnostic delay was defined as time >1 year from the onset of symptoms to the confirmed diagnosis for patients with UC and 2 years for patients with CD. Statistical analysis was performed with the SPSS v.24 program. A value of p ≤ 0.05 was taken as significant. Results The delay at diagnosis decreased significantly by 24.9% in the last 4 decades. The factors associated with the diagnostic delay were proctitis in UC, clinical course >2 relapses per year and IBD surgeries for CD. We found a delay at diagnosis in 35.2% of IBD patients in the public versus 16.9% in the private health care system (p = 0.00001). Conclusions We found a significant diagnosis delay of IBD in 35.2% from the public health care system versus 16.9% in the private health care system.
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Affiliation(s)
- Jesús K. Yamamoto-Furusho
- Inflammatory Bowel Disease Clinic, Department of Gastroenterology, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Mexico City, Mexico
- Gastroenterology and Obesity Service, Médica Sur Hospital, Mexico City, Mexico
- *Jesús K. Yamamoto-Furusho,
| | - Norma N. Parra-Holguín
- Inflammatory Bowel Disease Clinic, Department of Gastroenterology, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Mexico City, Mexico
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27
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Yanai H, Levine A, Hirsch A, Boneh RS, Kopylov U, Eran HB, Cohen NA, Ron Y, Goren I, Leibovitzh H, Wardi J, Zittan E, Ziv-Baran T, Abramas L, Fliss-Isakov N, Raykhel B, Gik TP, Dotan I, Maharshak N. The Crohn's disease exclusion diet for induction and maintenance of remission in adults with mild-to-moderate Crohn's disease (CDED-AD): an open-label, pilot, randomised trial. Lancet Gastroenterol Hepatol 2021; 7:49-59. [PMID: 34739863 DOI: 10.1016/s2468-1253(21)00299-5] [Citation(s) in RCA: 118] [Impact Index Per Article: 29.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 08/05/2021] [Accepted: 08/06/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND The Crohn's disease exclusion diet (CDED) with partial enteral nutrition is effective for induction of remission in children with mild-to-moderate Crohn's disease. We aimed to assess the CDED in adults with Crohn's disease. METHODS We did an open-label, pilot randomised trial at three medical centres in Israel. Eligible patients were biologic naive adults aged 18-55 years with mild-to-moderate Crohn's disease (defined by a Harvey-Bradshaw Index score of 5-14 points), a maximal disease duration of 5 years, with active disease on colonoscopy, or imaging with elevated inflammatory markers (C-reactive protein >5 mg/L or faecal calprotectin concentration >200 μ/g). Patients were randomly assigned (1:1) to CDED plus partial enteral nutrition or CDED alone for 24 weeks. Randomisation was via block randomisation (block sizes of six) using sealed, numbered, and opaque envelopes. Patients and investigators were aware of which group patients were assigned to due to the nature of the different interventions. The primary endpoint was clinical remission, defined as a Harvey-Bradshaw Index score of less than 5 at week 6. The primary endpoint was assessed in the intention-to-treat (ITT) population, which included all patients who used the dietary therapy for at least 48 h. We report results of the final analysis. This trial is registered with ClinicalTrials.gov, NCT02231814. FINDINGS Between Jan 12, 2017, and May 11, 2020, 91 patients were screened, of whom 44 were randomly assigned to the CDED plus partial enteral nutrition group (n=20) or CDED alone group (n=24). 19 patients in the CDED plus partial enteral nutrition group and 21 patients in the CDED alone group received the allocated intervention for at least 48 h and thus were included in the ITT analysis. At week 6, 13 (68%) of 19 patients in the CDED plus partial enteral nutrition group and 12 (57%) of 21 patients in the CDED group had achieved clinical remission (p=0·4618). Among the 25 patients in remission at week 6, 20 (80%) were in sustained remission at week 24 (12 patients in the CDED plus partial enteral nutrition group and eight in the CDED alone group). 14 (35%) of 40 patients were in endoscopic remission at week 24 (eight patients in the CDED plus partial enteral nutrition group and six in the CDED alone group). No serious adverse events or treatment-related adverse events were reported in either group. INTERPRETATION CDED with or without partial enteral nutrition was effective for induction and maintenance of remission in adults with mild-to-moderate biologic naive Crohn's disease and might lead to endoscopic remission. These data suggest that CDED could be used for mild-to-moderate active Crohn's disease and should be assessed in a powered randomised controlled trial. FUNDING Azrieli Foundation and Nestle Health Science.
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Affiliation(s)
- Henit Yanai
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | - Arie Levine
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Paediatric Gastroenterology Unit, Wolfson Medical Center, Holon, Israel
| | - Ayal Hirsch
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Gastroenterology and Hepatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Rotem Sigall Boneh
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Israel PIBD Research Center, Wolfson Medical Center, Holon, Israel
| | - Uri Kopylov
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Gastroenterology, Sheba Medical Center, Ramat-Gan, Israel
| | - Hagar Banai Eran
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Nathaniel A Cohen
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Gastroenterology and Hepatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Yulia Ron
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Gastroenterology and Hepatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Idan Goren
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Haim Leibovitzh
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Joram Wardi
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Gastroenterology Institute, Wolfson Medical Center, Holon, Israel
| | - Eran Zittan
- The Abraham and Sonia Rochlin IBD Unit, Department of Gastroenterology, Emek Medical Center, Afula, Israel; Rappaport Faculty of Medicine Technion-Israel Institute of Technology, Haifa, Israel
| | - Tomer Ziv-Baran
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Lee Abramas
- Israel PIBD Research Center, Wolfson Medical Center, Holon, Israel
| | - Naomi Fliss-Isakov
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Gastroenterology and Hepatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Barbara Raykhel
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
| | - Tamar Pfeffer Gik
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Iris Dotan
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Nitsan Maharshak
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Gastroenterology and Hepatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
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Narula N, Wong ECL, Dulai PS, Marshall JK, Colombel JF, Reinisch W. Outcomes of Passable and Non-passable Strictures in Clinical Trials of Crohn's Disease: A Post-hoc Analysis. J Crohns Colitis 2021; 15:1649-1657. [PMID: 33693522 DOI: 10.1093/ecco-jcc/jjab045] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND AND AIMS There is paucity of evidence on the reversibility of Crohn's disease [CD]-related strictures treated with therapies. We aimed to describe the clinical and endoscopic outcomes of CD patients with non-passable strictures. METHODS This was a post-hoc analysis of three large CD clinical trial programmes examining outcomes with infliximab, ustekinumab, and azathioprine, which included data on 576 patients including 105 with non-passable strictures and 45 with passable strictures, as measured using the Simple Endoscopic Score for Crohn's Disease [SES-CD]. The impact of non-passable strictures on achieving clinical remission [CR] and endoscopic remission [ER] was assessed using multivariate logistic regression models. CR was defined as a Crohn's Disease Activity Index [CDAI] <150, clinical response as a CDAI reduction of ≥100 points, and ER as SES-CD score <3. RESULTS After 1 year of treatment, patients with non-passable strictures demonstrated the ability to achieve passable or no strictures in 62.5% of cases, with 52.4% and 37.5% attaining CR and ER, respectively. However, patients with non-passable strictures at baseline were less likely to demonstrate symptom improvement compared with those with passable or no strictures, with reduced odds of 1-year CR (adjusted odds ratio [aOR] 0.17, 95% CI 0.03-0.99, p = 0.048). No significant differences were observed between patients with non-passable strictures at baseline and those with passable or no strictures in rates of ER [aOR 0.82, 95% CI 0.23-2.85, p = 0.751] at 1 year. CONCLUSIONS Patients with non-passable strictures can achieve symptomatic and endoscopic remission when receiving therapies used to treat CD, although they are less likely to obtain CR compared with patients without non-passable strictures. These findings support the importance of balancing the presence of non-passable strictures in trial arms.
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Affiliation(s)
- Neeraj Narula
- Department of Medicine [Division of Gastroenterology] and Farncombe Family Digestive Health Research Institute, M cmaster University, Hamilton, ON, Canada
| | - Emily C L Wong
- Department of Medicine [Division of Gastroenterology] and Farncombe Family Digestive Health Research Institute, M cmaster University, Hamilton, ON, Canada
| | - Parambir S Dulai
- Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA
| | - John K Marshall
- Department of Medicine [Division of Gastroenterology] and Farncombe Family Digestive Health Research Institute, M cmaster University, Hamilton, ON, Canada
| | - Jean-Frederic Colombel
- Division of Gastroenterology; Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Walter Reinisch
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
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Abstract
Twenty-five years ago the field was revolutionized by the introduction of infliximab as the first hybrid anti-TNF-antibody. Subsequently, other humanized anti-TNFs were developed and marketed, followed by antibodies to new targets including integrins (vedolizumab) and interleukin 12/23 (ustekinumab). All these so-called biologicals were shown in registrational trials to induce remission superior to placebo but consistently were effective in only a minority of patients. Even though in most trials only the responders were selected to continue on the respective medication for maintenance, many experienced a secondary loss of response and only a minority of usually <25% of the initial cohort achieved long-term (1 year) remission. In 'real life studies', the outcome was somewhat better, probably due to proper selection of patients and open, mostly retrospective study designs. A clear benefit of biologicals is apparent in otherwise treatment refractory patients, in extraintestinal manifestations and in Crohn´s disease (CD) with fistulizing complications. Biologicals achieve mucosal healing (MH) more often than corticosteroids or thiopurines, and MH is associated with improved prognosis. However, this does not justify escalating treatment until MH is reached since controlled trials proving this point of 'treat to target' are lacking both in ulcerative colitis and CD. Surgical rates have decreased with increasing use of biologicals, but disease progression has not been proven to improve. With the exception of opportunistic infections, serious adverse events are rare. In conclusion, biologicals have changed the scene considerably and expanded our armamentarium, but there is also a marketing hype fostering expectations without evidence.
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Mantzaris GJ, Zeglinas C, Theodoropoulou A, Koutroubakis I, Orfanoudaki E, Katsanos K, Christodoulou D, Michalopoulos G, Tzouvala M, Moschovis D, Michopoulos S, Zampeli E, Soufleris K, Ilias A, Chatzievangelinou C, Kyriakakis A, Antachopoulou K, Karmiris K. The Effect of Early vs Delayed Initiation of Adalimumab on Remission Rates in Patients With Crohn's Disease With Poor Prognostic Factors: The MODIFY Study. CROHN'S & COLITIS 360 2021; 3:otab064. [PMID: 36777275 PMCID: PMC9802300 DOI: 10.1093/crocol/otab064] [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: 06/09/2021] [Indexed: 12/07/2022] Open
Abstract
Background Data on the effectiveness of anti-tumor necrosis factor medications in patients with Crohn's disease (CD) with poor prognostic factors (PPFs) are scarce. This study aimed to generate real-world evidence on the effect of early (≤24 months after diagnosis) vs delayed (>24 months) initiation of adalimumab (ADL) on the 26-week remission rate (Harvey-Bradshaw Index ≤4) in these patients. Methods This multicentre, retrospective, chart review study performed in 10 Greek hospitals enrolled adult patients with moderate to severe CD (Harvey-Bradshaw Index ≥8) with ≥3 PPFs who were initiated on ADL ≥12 months before enrollment. A sample size of 164 patients (early:delayed cohort allocation ratio, 30:70) was required to address the primary endpoint. Results Eligible patients (n = 171) were consecutively enrolled. In the early vs delayed cohorts, the 26-week remission rates (off-steroids) using the last-observation-carried-forward imputation method were 60.7% (37/61) vs 47.2% (50/106), respectively (Δ = 13.5%, P = .044). The respective remission rates were 61.2% vs 42.4% among anti-tumor necrosis factor-naive patients (P = .023) and 58.3% vs 53.2% among anti-tumor necrosis factor-experienced patients (P = .374). The 52-week remission rates using as-observed data were 78.8% and 60.3%, and the intestinal resection rates were 6.5% and 11.9% in the early vs delayed ADL cohorts, respectively. Conclusions Patients with CD with PPFs who received early vs delayed treatment with ADL achieved higher clinical response and remission rates. This effect was more pronounced in those patients who were bio-naive and steroid-dependent/refractory with concurrent extraintestinal manifestations than those who were not.
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Affiliation(s)
- Gerassimos J Mantzaris
- Department of Gastroenterology, General Hospital of Athens “Evaggelismos”, Athens, Greece,Address correspondence to: Gerassimos J. Mantzaris, MD, PhD, Department of Gastroenterology, General Hospital of Athens “Evaggelismos”, 45-47 Ipsilantou St., 10676, Athens, Attiki, Greece ()
| | | | - Angeliki Theodoropoulou
- Department of Gastroenterology, General Hospital of Heraklion “Venizeleio-Pananeio”, Heraklion, Crete, Greece
| | | | - Eleni Orfanoudaki
- Department of Gastroenterology, University Hospital of Heraklion, Crete, Greece
| | - Konstantinos Katsanos
- Department of Gastroenterology, Pathology Unit, University General Hospital of Ioannina, Ioannina, Greece
| | - Dimitrios Christodoulou
- Department of Gastroenterology, Pathology Unit, University General Hospital of Ioannina, Ioannina, Greece
| | | | - Maria Tzouvala
- Department of Gastroenterology, General Hospital of Nikaia & Piraeus “Agios Panteleimon”-General Hospital Dytikis Attikis “Agia Varvara”, Nikaia, Greece
| | - Dimitrios Moschovis
- Department of Gastroenterology, General Hospital of Nikaia & Piraeus “Agios Panteleimon”-General Hospital Dytikis Attikis “Agia Varvara”, Nikaia, Greece
| | - Spyridon Michopoulos
- Department of Gastroenterology, Pathology Unit, General Hospital of Athens “Alexandra”, Athens, Greece
| | - Evanthia Zampeli
- Department of Gastroenterology, Pathology Unit, General Hospital of Athens “Alexandra”, Athens, Greece
| | - Konstantinos Soufleris
- Department of Gastroenterology-Oncology, Pathology Unit, Anticancer Hospital of Thessaloniki “Theageneio”, Thessaloniki, Greece
| | - Anastasios Ilias
- Department of Gastroenterology, Pathology Unit, General Hospital of Thessaloniki “G. Papanikolaou”, Thessaloniki, Greece
| | | | | | | | - Konstantinos Karmiris
- Department of Gastroenterology, General Hospital of Heraklion “Venizeleio-Pananeio”, Heraklion, Crete, Greece
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Schnitzler F, Seitz T, Tillack-Schreiber C, Lange S, Waggershauser C, Ochsenkühn T. Early Start of Infliximab in Crohn's Disease Increases Rates of Endoscopic Remission and Decreases Stenosis Formation: Experiences From a Single Center Cohort. CROHN'S & COLITIS 360 2021; 3:otab060. [PMID: 36776655 PMCID: PMC9802408 DOI: 10.1093/crocol/otab060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Indexed: 11/13/2022] Open
Abstract
Background Over 10 years ago, the step-up/top-down trial demonstrated favorable outcomes of Crohn's disease (CD) after early initiation of infliximab (IFX) in patients with CD. However, data on long-term effects of this treatment strategy in daily clinical practice are scarce. Methods This retrospective study investigated effects of early (<24 months after diagnosis) versus late intervention (>24 months) of IFX in CD on endoscopic remission (ER) rates, surgery rates, and course of CD, long term. Results Overall, 242 CD patients (94 early, 148 late intervention) were started on IFX and followed for 24 months. Sixty-one patients with early and 86 with late intervention underwent endoscopy after start of IFX. After IFX induction, 90.3% of patients with early versus 87.8% with late intervention were in clinical remission (P = .676), compared to 89.1% versus 85.8% after 24 months (P = .554). Almost half of patients with early IFX (45.9%, n = 28/61) achieved ER within 24 months compared to only one forth with late IFX intervention (25.6%, n = 22/86, P = .013). In addition, significantly less patients with early IFX intervention (9.8%, n = 6/61) developed intestinal stenosis during 24 months follow-up compared to late IFX start (29.1%, n = 25/86, P = .007). Logistic regression revealed early IFX intervention as only relevant factor achieving ER with an odds ratio of 2.386 (95% confidence interval [1.1180; 4.825], P = .016). Conclusions Our data on early IFX therapy in CD support early IFX intervention with more patients achieving ER, and less patients developing stricturing disease behavior. Early IFX intervention could therefore change the course of CD.
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Affiliation(s)
- Fabian Schnitzler
- Department of Medicine II—Grosshadern, Ludwig-Maximilians-University (LMU), Munich, Germany,Praxisklinik München-Pasing, Munich, Germany,Address correspondence to: Fabian Schnitzler, MD, Praxisklinik München-Pasing, D-81245 Munich, Germany ()
| | - Theresia Seitz
- Department of Medicine II—Grosshadern, Ludwig-Maximilians-University (LMU), Munich, Germany,IBD Center Munich, Munich, Germany,Helios Klinikum Pasing, Munich, Germany
| | | | | | - Constanze Waggershauser
- Department of Medicine II—Grosshadern, Ludwig-Maximilians-University (LMU), Munich, Germany,IBD Center Munich, Munich, Germany
| | - Thomas Ochsenkühn
- Department of Medicine II—Grosshadern, Ludwig-Maximilians-University (LMU), Munich, Germany,IBD Center Munich, Munich, Germany
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Hedin CRH, Sonkoly E, Eberhardson M, Ståhle M. Inflammatory bowel disease and psoriasis: modernizing the multidisciplinary approach. J Intern Med 2021; 290:257-278. [PMID: 33942408 DOI: 10.1111/joim.13282] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 01/11/2021] [Accepted: 01/18/2021] [Indexed: 12/11/2022]
Abstract
Psoriasis and inflammatory bowel disease (IBD) are immune-mediated diseases occurring in barrier organs whose main task is to protect the organism from attack. These disorders are highly prevalent especially in northern Europe where psoriasis has a prevalence of around 3-4% and IBD around 0.3%. The prevalence of IBD in North America has been estimated at around 0.4%. The total incidence rates in northern Europe have been estimated at around 6 for Crohn's disease and 11 for ulcerative colitis per 100 000 person-years, compared with an incidence rate of around 280 per 100 000 person-years for psoriasis. Both diseases are less common in countries with a lower index of development. The rise in IBD appears to occur as populations adopt a westernized lifestyle, whereas psoriasis seems more stable and prevalence differences may derive more from variation in genetic susceptibility. The gut microbiota is clearly an important driver of IBD pathogenesis; in psoriasis, changes in gut and skin microbiota have been reported, but it is less clear whether and how these changes contribute to the pathogenesis. Large studies show that most identified genes are involved in the immune system. However, psoriasis and IBD are highly heterogeneous diseases and there is a need for more precise and deeper phenotyping to identify specific subgroups and their genetic, epigenetic and molecular signatures. Epigenetic modifications of DNA such as histone modifications, noncoding RNA effects on transcription and translation and DNA methylation are increasingly recognized as the mechanism underpinning much of the gene-environment interaction in the pathogenesis of both IBD and psoriasis. Our understanding of underlying pathogenetic mechanisms has deepened fundamentally over the past decades developing hand in hand with novel therapies targeting pathways and proinflammatory cytokines incriminated in disease. There is not only substantial overlap between psoriasis and IBD, but also there are differences with implication for therapy. In psoriasis, drugs targeting interleukin-23 and interleukin-17 have shown superior efficacy compared with anti-TNFs, whilst in IBD, drugs targeting interleukin-17 may be less beneficial. The therapeutic toolbox for psoriasis is impressive and is enlarging also for IBD. Still, there are unmet needs reflecting the heterogeneity of both diseases and there is a need for closer molecular diagnostics to allow for the development of precise therapeutics.
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Affiliation(s)
- C R H Hedin
- From the, Department of Medicine, Karolinska Institutet, Solna, Stockholm, Sweden.,Division of Gastroenterology, Medical Unit Gastroenterology, Dermatovenereology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
| | - E Sonkoly
- From the, Department of Medicine, Karolinska Institutet, Solna, Stockholm, Sweden.,Division of Dermatology, Medical Unit Gastroenterology, Dermatovenereology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
| | - M Eberhardson
- From the, Department of Medicine, Karolinska Institutet, Solna, Stockholm, Sweden.,Department of Gastroenterology, University Hospital in Linkoping, Linkoping, Sweden
| | - M Ståhle
- From the, Department of Medicine, Karolinska Institutet, Solna, Stockholm, Sweden.,Division of Dermatology, Medical Unit Gastroenterology, Dermatovenereology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
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Yanai H, Goren I, Godny L, Maharshak N, Ron Y, Avni Biron I, Leibovitzh H, Banai Eran H, Aharoni Golan M, Rabinowitz K, Ziv Baran T, Lavie I, Yadgar K, Zonensain K, Kopylov U, Ben Horin S, Eliakim R, Waterman M, Chowers Y, Ben-Shachar S, Dotan I. Early Indolent Course of Crohn's Disease in Newly Diagnosed Patients Is Not Rare and Possibly Predictable. Clin Gastroenterol Hepatol 2021; 19:1564-1572.e5. [PMID: 32629126 DOI: 10.1016/j.cgh.2020.06.069] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Revised: 05/28/2020] [Accepted: 06/23/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The early stages of Crohn's disease (CD) course are heterogeneous, and it is a challenge to predict the course of disease in patients with new diagnosis. METHODS We performed an observational longitudinal study of 156 adults (79 male; median age, 27.7 years; 57 treatment naïve) with newly diagnosed CD (within 6 months of enrollment), referred from medical centers and community clinics in Israel from 2013 through 2017. Study participants each received semi-annual scheduled evaluations. Indolent disease was defined as a disease course without need for strict interventions to control complicated course of CD (hospitalization or surgery, or decision to start steroid, immunomodulator, or biologic therapy). Cox regression and receiver operating characteristic analyses were used to identify factors associated with early indolent or complicated course of CD. We validated our findings in an independent cohort of patients with CD from a separate medical center in Israel in 2018. RESULTS Over a median follow-up period of 17.2 months (interquartile range, 8.8-23.8 months), 52 patients (33.3%) had an indolent course of CD, 29 (18.5%) required hospitalizations, and 75 (48%) were recommended to start steroid, immunomodulator, or biologic therapies. The median time to first intervention was 3.4 months (95% CI, 2.4-4.4). We developed a model based on clinical factors that identified 4 factors associated with complicated course in treatment-naïve patients: body mass index <25 kg/m2 (hazard ratio [HR], 2.45; 95% CI, 1.07-5.43; P = .033), serum level of vitamin B12 <350 pg/mL (HR, 2.78; 95% CI, 1.21-6.41; P = .016), white blood cells ≥7 × 103/μL (HR, 2.419; 95% CI, 1.026-5.703; P = .044), and serum level of ALT ≥25 IU/L (HR, 2.680; 95% CI, 1.186-6.058; P = .018). This model discriminated between patients with vs without a complicated course of disease with 90% and 89% accuracy at 6 and 12 months after diagnosis, respectively. A validation cohort demonstrated a discriminatory ability of 79% at 3 months after diagnosis, and a nomogram was constructed. CONCLUSIONS In an observational longitudinal study of 156 patients with newly diagnosed CD, we found that one third have an early indolent course of disease. We identified factors that can be measured at diagnosis to identify patients at risk for an early complicated course-these might be used in patient management and selection of treatment.
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Affiliation(s)
- Henit Yanai
- IBD Center, Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | - Idan Goren
- IBD Center, Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Lihi Godny
- IBD Center, Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Nitsan Maharshak
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; IBD Center, Department of Gastroenterology and Liver Diseases, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Yulia Ron
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; IBD Center, Department of Gastroenterology and Liver Diseases, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Irit Avni Biron
- IBD Center, Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Haim Leibovitzh
- IBD Center, Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Hagar Banai Eran
- IBD Center, Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Maya Aharoni Golan
- IBD Center, Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Keren Rabinowitz
- IBD Center, Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Tomer Ziv Baran
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Epidemiology and Preventive Medicine, School of Public Health, Tel Aviv University, Tel Aviv, Israel
| | - Inbar Lavie
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Karin Yadgar
- IBD Center, Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
| | - Keren Zonensain
- IBD Center, Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
| | - Uri Kopylov
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel
| | - Shomron Ben Horin
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel; Sun Yat-Sen University, Guangzhou, China
| | - Rami Eliakim
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel
| | - Matti Waterman
- Department of Gastroenterology, Rambam Health Care Campus and Bruce Rappaport School of Medicine, Technion Institute of Technology, Haifa, Israel
| | - Yehuda Chowers
- Department of Gastroenterology, Rambam Health Care Campus and Bruce Rappaport School of Medicine, Technion Institute of Technology, Haifa, Israel
| | - Shay Ben-Shachar
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Clalit Research Institute, Ramat-Gan, Israel
| | - Iris Dotan
- IBD Center, Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Rodríguez-Lago I, Barreiro-de Acosta M. Look at Both Sides of the Coin in Determining Risk of Complicated Crohn's Disease. Clin Gastroenterol Hepatol 2021; 19:1503-1504. [PMID: 33249022 DOI: 10.1016/j.cgh.2020.07.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 07/14/2020] [Indexed: 02/07/2023]
Affiliation(s)
- Iago Rodríguez-Lago
- Gastroenterology Department, Hospital de Galdakao, Biocruces Bizkaia Health Research Institute, Barakaldo, Spain
| | - Manuel Barreiro-de Acosta
- Gastroenterology Department, Hospital Clínico Universitario de Santiago de Compostela, A Coruña, Spain
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Yanai H, Goren I, Dotan I. Reply. Clin Gastroenterol Hepatol 2021; 19:1504-1505. [PMID: 33249028 DOI: 10.1016/j.cgh.2020.08.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Revised: 08/10/2020] [Accepted: 08/10/2020] [Indexed: 02/07/2023]
Affiliation(s)
- Henit Yanai
- IBD Center, Division of Gastroenterology, Rabin Medical Center, Petah-Tikva, Israel, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Idan Goren
- IBD Center, Division of Gastroenterology, Rabin Medical Center, Petah-Tikva, Israel, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Iris Dotan
- IBD Center, Division of Gastroenterology, Rabin Medical Center, Petah-Tikva, Israel, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Vuyyuru SK, Kante B, Kumar P, Sahu P, Kedia S, Ranjan MK, Sharma R, Panwar R, Makharia G, Ahuja V. Real world analysis on the efficacy and safety of anti-tumor necrosis factor therapy in patients with stricturing Crohn's disease. Sci Rep 2021; 11:11704. [PMID: 34083575 PMCID: PMC8175366 DOI: 10.1038/s41598-021-90660-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 04/22/2021] [Indexed: 12/22/2022] Open
Abstract
Crohn's disease (CD) is often complicated by strictures and associated with increased risk for surgery. Inflammatory strictures respond to medical therapy, and anti-tumor necrosis factor (TNF) therapy is often used after the failure of steroids. However, data on efficacy of anti-TNF therapy in stricturing CD is limited. We retrospectively analysed the records of patients with stricturing CD who were treated with anti-TNF therapy and were prospectively followed from January 2005 to July 2020. Treatment success was defined as continuation of anti-TNF without the requirement for steroids or parenteral nutrition, switch to other anti-TNF, endoscopic dilation, surgery and severe adverse events leading to the withdrawal of anti-TNF. Fifty-nine patients were included [50-infliximab, 9-adalimumab; mean age-30.1 ± 15 years; males-69.5%; median disease duration-124 (range 30-396) months; median follow-up duration-42 (range 8-180) months]. Ileum was the most common site of stricture (69.5%), 20.3% of patients had colonic strictures, and 64.4% had multiple strictures. 55.9% of patients were steroid dependent and 37.3% were steroid refractory. The median duration of anti-TNF therapy was 14 (range 2-96) months, and 54.2% (n = 32) patients received concomitant immunomodulators. 88% improved with induction (11.8% primary non-response), secondary loss of response was seen in 52.2%, and the cumulative probability of treatment success at 1, 2 and 5 years was 69%, 51%, and 28% respectively. Anaemia at presentation predicted poor response. Only 30% of patients retained biologics on long-term (lack of response, cost, adverse events). 16.9% had adverse events, the commonest being reactivation of tuberculosis (5.1%). Anti-TNF therapy is associated with good short-term treatment success with modest long-term response in stricturing CD.
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Affiliation(s)
- Sudheer K Vuyyuru
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delh, 110029, India
| | - Bhaskar Kante
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delh, 110029, India
| | - Peeyush Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delh, 110029, India
| | - Pabitra Sahu
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delh, 110029, India
| | - Saurabh Kedia
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delh, 110029, India
| | - Mukesh Kumar Ranjan
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delh, 110029, India
| | - Raju Sharma
- Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India
| | - Rajesh Panwar
- Department of Gastrointestinal Surgery and Liver Transplantation, All India Institute of Medical Sciences, New Delhi, India
| | - Govind Makharia
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delh, 110029, India
| | - Vineet Ahuja
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delh, 110029, India.
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Yassin S, Isakov NF, Ron Y, Cohen NA, Hirsch A, Maharshak N. A watchful waiting approach for newly diagnosed Crohn's disease patients with an inflammatory phenotype. Int J Colorectal Dis 2021; 36:735-743. [PMID: 33404768 DOI: 10.1007/s00384-020-03811-8] [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] [Accepted: 11/23/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND An early treat-to-target approach in Crohn's disease (CD) patients is recommended to avoid complications. However, CD may not always progress despite lack of treatment, thus exposing some patients to unnecessary side effects. We aimed to examine whether newly diagnosed CD patients with an inflammatory phenotype can benefit from a watchful waiting approach. METHODS This retrospective cohort study followed CD patients with an inflammatory phenotype who were diagnosed between 2010 and 2015 and followed for at least 1 year. A watchful waiting approach was defined as maintenance therapy with 5-ASA medication only or no treatment during the first year of diagnosis or longer. Disease complications were defined as need for surgery or change in disease phenotype. RESULTS Eighty-six patients were included and followed-up for 57.0 ± 29.0 months. Thirty-seven patients were managed with a watchful waiting approach and 49 with an early therapeutic intervention. The majority of patients (83.8%) in the watchful waiting group did not develop disease complications. In this group, there was no difference in clinical disease severity (stools per day, 2.7 ± 1.7 vs 3.3 ± 1.0, P = 0.39; abdominal pain, 74.2 vs 50.0%, P = 0.24) between those who did not develop complications and those who did. Smoking was associated with a complicated course (multivariate analysis: OR = 1.98, 95% CI 1.06-3.71, P = 0.03). CONCLUSIONS A watchful waiting approach of newly diagnosed CD patients with an inflammatory phenotype may be a feasible option, with low long-term complication rate specifically in nonsmoking patients.
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Affiliation(s)
- Sharif Yassin
- IBD Unit, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, 6 Weizman Street, 6423906, Tel Aviv, Israel.,Department of Internal Medicine "B", Tel Aviv Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Naomi Fliss Isakov
- IBD Unit, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, 6 Weizman Street, 6423906, Tel Aviv, Israel
| | - Yulia Ron
- IBD Unit, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, 6 Weizman Street, 6423906, Tel Aviv, Israel
| | - Nathaniel Aviv Cohen
- IBD Unit, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, 6 Weizman Street, 6423906, Tel Aviv, Israel
| | - Ayal Hirsch
- IBD Unit, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, 6 Weizman Street, 6423906, Tel Aviv, Israel
| | - Nitsan Maharshak
- IBD Unit, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, 6 Weizman Street, 6423906, Tel Aviv, Israel.
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Zhu M, Feng Q, Xu X, Qiao Y, Cui Z, Yan Y, Ran Z. Efficacy of early intervention on the bowel damage and intestinal surgery of Crohn's disease, based on the Lémann index. BMC Gastroenterol 2020; 20:421. [PMID: 33308166 PMCID: PMC7733289 DOI: 10.1186/s12876-020-01575-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Accepted: 12/07/2020] [Indexed: 01/12/2023] Open
Abstract
Background Clinicians aim to prevent progression of Crohn’s disease (CD); however, many patients require surgical resection because of cumulative bowel damage. The aim of this study was to evaluate the impact of early intervention on bowel damage in patients with CD using the Lémann Index and to identify bowel resection predictors.
Methods We analyzed consecutive patients with CD retrospectively. The Lémann Index was determined at the point of inclusion and at follow-up termination. The Paris definition was used to subdivide patients into early and late CD groups. Results We included 154 patients, comprising 70 with early CD and 84 with late CD. After follow-up for 17.0 months, more patients experienced a decrease in the Lémann Index (61.4% vs. 42.9%), and fewer patients showed an increase in the Lémann Index (20% vs. 35.7%) in the early compared with the late CD group. Infliximab and other therapies reversed bowel damage to a greater extent in early CD patients than in late CD patients. Twenty-two patients underwent intestinal surgery, involving 5 patients in the early CD group and 17 patients in the late CD group. Three independent predictors of bowel resection were identified: baseline Lémann index ≥ 8.99, disease behavior B1, and history of intestinal surgery. Conclusions Early intervention within 18 months after CD diagnosis could reverse bowel damage and decrease short-term intestinal resection. Patients with CD with a history of intestinal surgery, and/or a Lémann index > 8.99 should be treated aggressively and monitored carefully to prevent progressive bowel damage.
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Affiliation(s)
- Mingming Zhu
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Qi Feng
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Xitao Xu
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Yuqi Qiao
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Zhe Cui
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yunqi Yan
- Department of Radiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Zhihua Ran
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.
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39
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Guasch M, Cañete F, Ordás I, Iglesias-Flores E, Clos A, Gisbert JP, Taxonera C, Vera I, Mínguez M, Guardiola J, Rivero M, Nos P, Gomollón F, Barrio J, de Francisco R, López-Sanromán A, Martín-Arranz MD, Garcia-Planella E, Camargo R, García-López S, de Castro L, Calvet X, Esteve M, Mañosa M, Domènech E. Changes in the requirement for early surgery in inflammatory bowel disease in the era of biological agents. J Gastroenterol Hepatol 2020; 35:2080-2087. [PMID: 32350906 DOI: 10.1111/jgh.15084] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Revised: 04/22/2020] [Accepted: 04/27/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIM Biological therapies may be changing the natural history of inflammatory bowel diseases (IBDs), reducing the need for surgical intervention. We aimed to assess whether the availability of anti-TNF agents impacts the need for early surgery in Crohn's disease (CD) and ulcerative colitis (UC). METHODS Retrospective, cohort study of patients diagnosed within a 6-year period before and after the licensing of anti-TNFs (1990-1995 and 2007-2012 for CD; 1995-2000 and 2007-2012 for UC) were identified in the ENEIDA Registry. Surgery-free survival curves were compared between cohorts. RESULTS A total of 7370 CD patients (2022 in Cohort 1 and 5348 in Cohort 2) and 8069 UC patients (2938 in Cohort 1 and 5131 in Cohort 2) were included. Immunosuppressants were used significantly earlier and more frequently in both CD and UC post-biological cohorts. The cumulative probability of surgery was lower in CD following anti-TNF approval (16% and 11%, 22% and 16%, and 29% and 19%, at 1, 3, and 5 years, respectively P < 0.0001), although not in UC (3% and 2%, 4% and 4%, and 6% and 5% at 1, 3, and 5 years, respectively; P = 0.2). Ileal involvement, older age at diagnosis and active smoking in CD, and extensive disease in UC, were independent risk factors for surgery, whereas high-volume IBD centers (in both CD and UC) and immunosuppressant use (in CD) were protective factors. CONCLUSIONS Anti-TNF availability was associated with a reduction in early surgery for CD (driven mainly by earlier and more widespread immunosuppressant use) but not in UC.
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Affiliation(s)
- Montserrat Guasch
- Hospital Universitari Germans Trias i Pujol (Badalona, Catalonia), Barcelona, Spain.,Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain
| | - Fiorella Cañete
- Hospital Universitari Germans Trias i Pujol (Badalona, Catalonia), Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Madrid), Madrid, Spain
| | - Ingrid Ordás
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Madrid), Madrid, Spain.,Hospital Clínic and IDIBAPS (Barcelona, Catalonia), Madrid, Spain
| | | | - Ariadna Clos
- Hospital Universitari Germans Trias i Pujol (Badalona, Catalonia), Barcelona, Spain
| | - Javier P Gisbert
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Madrid), Madrid, Spain.,Hospital de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (Madrid), Madrid, Spain
| | - Carlos Taxonera
- Hospital Clínico San Carlos, Instituto de Investigación del Hospital Clínico San Carlos (IdISSC) (Madrid), Madrid, Spain
| | - Isabel Vera
- Hospital Universitario Puerta de Hierro (Madrid), Majadahonda, Spain
| | - Miguel Mínguez
- H. Clínico de Valencia i Universitat de València (València), Valencia, Spain
| | - Jordi Guardiola
- Hospital Universitari de Bellvitge IDIBELL and Universitat de Barcelona (L'Hospitalet del Llobregat, Catalonia), Llobregat, Spain
| | - Montserrat Rivero
- Hospital Marqués de Valdecilla and IDIVAL (Santander), Santander, Spain
| | - Pilar Nos
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Madrid), Madrid, Spain.,Hospital Universitari i Politècnic La Fe (Valencia), Valencia, Spain
| | - Fernando Gomollón
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Madrid), Madrid, Spain.,IIS Aragón, Hospital Clínico Lozano Blesa (Zaragoza), Zaragoza, Spain
| | | | - Ruth de Francisco
- Hospital Universitario Central de Asturias e Instituto de Investigación Sanitaria del Principado de Asturias (ISPA) (Oviedo), Spain
| | | | | | | | | | | | | | - Xavier Calvet
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Madrid), Madrid, Spain.,Hospital Parc Taulí (Sabadell, Catalonia), Spain
| | - Maria Esteve
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Madrid), Madrid, Spain.,Hospital Mútua Terrassa (Terrassa, Catalonia), Spain
| | - Míriam Mañosa
- Hospital Universitari Germans Trias i Pujol (Badalona, Catalonia), Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Madrid), Madrid, Spain
| | - Eugeni Domènech
- Hospital Universitari Germans Trias i Pujol (Badalona, Catalonia), Barcelona, Spain.,Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Madrid), Madrid, Spain
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Hamdeh S, Aziz M, Altayar O, Olyaee M, Murad MH, Hanauer SB. Early vs Late Use of Anti-TNFa Therapy in Adult Patients With Crohn Disease: A Systematic Review and Meta-Analysis. Inflamm Bowel Dis 2020; 26:1808-1818. [PMID: 32064534 DOI: 10.1093/ibd/izaa031] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Indexed: 12/11/2022]
Abstract
OBJECTIVES While anti-tumor necrosis factor alpha (anti-TNFa) therapies for Crohn disease (CD) were initially introduced in 1998 for biologic therapies are often introduced after a minimum of 6 years after diagnosis. The benefit of anti-TNFa early in the course of CD is still controversial, with some studies showing better outcomes but others not. To determine whether earlier introduction of anti-TNFa therapy improves efficacy in clinical trials or clinical series, we aimed to perform a meta-analysis comparing early vs late anti-TNFa use in the management of CD. METHODS A comprehensive search of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus was conducted from each database's inception to November 3, 2019. We included comparative studies of early vs late use of anti-TNFa therapy in adult patients with CD. RESULTS Eleven studies were included in the analysis, with a total of 2501 patients. Meta-analysis demonstrated that the early use of anti-TNFa was associated with a statistically significant decrease in the need for surgery (relative risk [RR] = 0.43; 95% confidence interval [CI], 0.26-0.69; I2 = 68%) and disease progression (RR = 0.51; 95% CI, 0.35-0.75; I2 = 61%). Early use also showed an increase in early remission (RR = 1.94; 95% CI, 1.54-2.46; I2 = 0%) and clinical response. There was no statistically significant difference in achieving late remission (RR = 1.39; 95% CI, 0.94-2.05; I2 = 65%) or mucosal healing (RR = 1.10; 95% CI, 0.63-1.91; I2 = 0%). CONCLUSION This systematic review suggests that using anti-TNFa earlier in the treatment of CD (within 3 years) may improve clinical outcomes compared to late administration in terms of achieving early clinical remission, clinical response, disease progression, and the need for surgery.
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Affiliation(s)
- Shadi Hamdeh
- University of Kansas Medical Center, Internal Medicine Department, Division of Gastroenterology and Hepatology, Kansas City, Kansas, USA
| | - Muhammad Aziz
- University of Toledo Medical Center, Department of Internal Medicine, Toledo, Ohio, USA
| | - Osama Altayar
- Washington University School of Medicine, Internal Medicine Department, Division of Gastroenterology and Hepatology, St. Louis, Missouri, USA
| | - Mojtaba Olyaee
- University of Kansas Medical Center, Internal Medicine Department, Division of Gastroenterology and Hepatology, Kansas City, Kansas, USA
| | - Mohammad Hassan Murad
- Mayo Clinic College of Medicine, Evidence-Based Practice Center, Rochester, Minnesota, USA
| | - Stephen B Hanauer
- Northwestern University Feinberg School of Medicine, Internal Medicine Department, Division of Gastroenterology and Hepatology, Chicago, Illinois, USA
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41
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Chronic inflammation and other changes are significant components of clinically fibrotic strictures in Crohn's disease: a histological study of resected strictures clinically characterized as noninflamed. Eur J Gastroenterol Hepatol 2020; 32:1432-1439. [PMID: 32639416 DOI: 10.1097/meg.0000000000001796] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Strictures related to Crohn's disease due to fibrosis are a result of an exaggerated tissue remodelling response to inflammation, characterized by accumulation of collagen-rich extracellular matrix produced by mesenchymal cells. OBJECTIVES The objective of this study was to characterize histological changes seen in resected 'fibrotic' strictures to better understand individual components of intestinal stenosis. METHODS We identified patients undergoing surgery for ileal Crohn's disease secondary to symptomatic stricturing disease (Montreal B2) using the histopathology database at Queen Elizabeth Hospital in Birmingham, UK, between 2012 and 2017. Phenotypic data were recorded and resection specimens reviewed. Two independent pathologists applied the semiquantitative scoring system previously developed by us to the microscopic images. Data were analyzed using the possible maximum total score (%PMTS). RESULTS Forty-eight patients (M = 25) were included. with median disease duration of 7 years (range 0.25-39 years); nearly two-thirds had ileocolonic distribution (L3). In this cohort, despite presurgery diagnosis of noninflamed fibrosis, chronic inflammation was noted to be a prominent component of all strictures. The histological scoring showed presence of several other prominent findings such as muscular hyperplasia and volume expansion.There was statistically significant positive correlation between chronic inflammation and fibrosis and muscular hyperplasia. CONCLUSION The histological features of Crohn's disease-related strictures show multiple changes in multiple layers and not simply fibrosis. In our cohort, despite the observation prior to surgery that strictures were clinically considered fibrotic, the finding of chronic inflammation as a dominant component at a histological level in the resection is important. The findings might suggest that one of the main drivers of progressive fibrosis is the inflammatory component, which probably is never fully resolved.
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42
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Rodríguez-Lago I, Hoyo JD, Pérez-Girbés A, Garrido-Marín A, Casanova MJ, Chaparro M, Fernández-Clotet A, Castro-Poceiro J, García MJ, Sánchez S, Ferreiro-Iglesias R, Bastón I, Piqueras M, de Careda LEIB, Mena R, Suárez C, Cordón JP, López-García A, Márquez L, Arroyo M, Alfambra E, Sierra M, Cano N, Delgado-Guillena P, Morales-Alvarado V, Aparicio JC, Guerra I, Aulló C, Merino O, Arranz L, Hidalgo MA, Llaó J, Plaza R, Molina G, Torres P, Pérez-Galindo P, Romero MG, Herrera-deGuise C, Armesto E, Mesonero F, Frago-Larramona S, Benítez JM, Calvo M, Martín MDCL, Elorza A, Larena A, Peña E, Rodríguez-Grau MDC, de Miguel-Criado J, Botella B, Olmos JA, López L, Aguirre U, Gisbert JP. Early treatment with anti-tumor necrosis factor agents improves long-term effectiveness in symptomatic stricturing Crohn's disease. United European Gastroenterol J 2020; 8:1056-1066. [PMID: 32723069 PMCID: PMC7724538 DOI: 10.1177/2050640620947579] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 07/10/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND There is limited evidence on the effectiveness of biological therapy in stricturing complications in patients with Crohn's disease. AIM The study aims to determine the effectiveness of anti-tumor necrosis factor (TNF) agents in Crohn's disease complicated with symptomatic strictures. METHODS In this multicentric and retrospective study, we included adult patients with symptomatic stricturing Crohn's disease receiving their first anti-TNF therapy, with no previous history of biological, endoscopic or surgical therapy. The effectiveness of the anti-TNF agent was defined as a composite outcome combining steroid-free drug persistence with no use of new biologics or immunomodulators, hospital admission, surgery or endoscopic therapy during follow-up. RESULTS Overall, 262 patients with Crohn's disease were included (53% male; median disease duration, 35 months, 15% active smokers), who received either infliximab (N = 141, 54%) or adalimumab (N = 121, 46%). The treatment was effective in 87% and 73% of patients after 6 and 12 months, respectively, and continued to be effective in 26% after a median follow-up of 40 months (IQR, 19-85). Nonetheless, 15% and 21% of individuals required surgery after 1 and 2 years, respectively, with an overall surgery rate of 32%. Postoperative complications were identified in 15% of patients, with surgical site infection as the most common. Starting anti-TNF therapy in the first 18 months after the diagnosis of Crohn's disease or the identification of stricturing complications was associated with a higher effectiveness (HR 1.62, 95% CI 1.18-2.22; and HR 1.55, 95% CI 1.1-2.23; respectively). Younger age, lower albumin levels, strictures located in the descending colon, concomitant aminosalicylates use or presence of lymphadenopathy were associated with lower effectiveness. CONCLUSIONS Anti-TNF agents are effective in approximately a quarter of patients with Crohn's disease and symptomatic intestinal strictures, and 68% of patients are free of surgery after a median of 40 months of follow-up. Early treatment and some potential predictors of response were associated with treatment success in this setting.
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Affiliation(s)
- Iago Rodríguez-Lago
- Hospital de Galdakao, Gastroenterology, Galdakao, Spain
- Biocruces Bizkaia Health Research Institute, Barakaldo,
Spain
| | - Javier Del Hoyo
- Hospital Universitari i Politècnic de La Fe, Gastroenterology,
Valencia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades
Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | | | | | - María José Casanova
- Centro de Investigación Biomédica en Red de Enfermedades
Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Hospital Universitario de La Princesa, Gastroenterology, Madrid,
Spain
- Instituto de Investigación Sanitaria Princesa (IIS-IP),
Universidad Autónoma de Madrid (UAM), Madrid, Spain
| | - María Chaparro
- Centro de Investigación Biomédica en Red de Enfermedades
Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Hospital Universitario de La Princesa, Gastroenterology, Madrid,
Spain
- Instituto de Investigación Sanitaria Princesa (IIS-IP),
Universidad Autónoma de Madrid (UAM), Madrid, Spain
| | - Agnès Fernández-Clotet
- Centro de Investigación Biomédica en Red de Enfermedades
Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Hospital Clinic, Gastroenterology, Barcelona, Spain
| | | | - María José García
- Hospital Universitario Marqués de Valdecilla, Gastroenterology,
Santander, Spain
| | - Sara Sánchez
- Hospital Universitario Marqués de Valdecilla, Radiology,
Santander, Spain
| | - Rocío Ferreiro-Iglesias
- Hospital Clínico Universitario de Santiago de Compostela,
Gastroenterology, Santiago de Compostela, Spain
| | - Iria Bastón
- Hospital Clínico Universitario de Santiago de Compostela,
Gastroenterology, Santiago de Compostela, Spain
| | - Marta Piqueras
- Consorci Sanitari de Terrassa, Gastroenterology, Terrassa,
Spain
| | | | - Raquel Mena
- Consorci Sanitari de Terrassa, Gastroenterology, Terrassa,
Spain
| | - Cristina Suárez
- Hospital Universitario La Paz, Gastroenterology, Madrid,
Spain
| | | | - Alicia López-García
- Hospital del Mar, Gastroenterology, Barcelona, Spain, and
Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
| | - Lucía Márquez
- Hospital del Mar, Gastroenterology, Barcelona, Spain, and
Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
| | - Maite Arroyo
- Centro de Investigación Biomédica en Red de Enfermedades
Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- IIS Aragón, Hospital Clínico Universitario Lozano Blesa,
Gastroenterology, Zaragoza, Spain
| | - Erika Alfambra
- Centro de Investigación Biomédica en Red de Enfermedades
Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- IIS Aragón, Hospital Clínico Universitario Lozano Blesa,
Gastroenterology, Zaragoza, Spain
| | - Mónica Sierra
- Complejo Asistencial Universitario de León, Gastroenterology,
León, Spain
| | - Noelia Cano
- Complejo Asistencial Universitario de León, Gastroenterology,
León, Spain
| | | | | | | | - Iván Guerra
- Hospital Universitario de Fuenlabrada, Gastroenterology,
Fuenlabrada, Spain, and Instituto de Investigación de La Paz (IdiPaz), Madrid,
Spain
| | - Carolina Aulló
- Hospital Universitario de Fuenlabrada, Radiology, Fuenlabrada,
Spain
| | - Olga Merino
- Hospital Universitario de Cruces, Gastroenterology, Barakaldo,
Spain
| | - Laura Arranz
- Hospital Ntra. Sra. Candelaria, Gastroenterology, Santa Cruz de
Tenerife, Spain
| | | | - Jordina Llaó
- Althaia, Xarxa Assistencial Universitària de Manresa,
Gastroenterology, Manresa, Spain
| | - Rocío Plaza
- Hospital Universitario Infanta Leonor, Gastroenterology,
Madrid, Spain
| | - Gema Molina
- Complejo Hospitalario Universitario de Ferrol,
Gastroenterology, Ferrol, Spain
| | - Paola Torres
- Hospital Universitario German Trias I Pujol, Gastroenterology,
Badalona, Spain
| | | | | | | | - Edisa Armesto
- Hospital San Agustín, Gastroenterology, Avilés, Spain
| | | | | | - José Manuel Benítez
- Hospital Universitario Reina Sofía, Gastroenterology, Córdoba,
Spain
- IMIBIC, Córdoba, Spain
| | - Marta Calvo
- Hospital Puerta de Hierro, Gastroenterology, Madrid,
Spain
| | | | - Ainara Elorza
- Hospital de Galdakao, Gastroenterology, Galdakao, Spain
- Biocruces Bizkaia Health Research Institute, Barakaldo,
Spain
| | | | - Elena Peña
- Hospital Royo Villanova, Gastroenterology, Zaragoza,
Spain
| | | | | | - Belén Botella
- Hospital Universitario Infanta Cristina, Gastroenterology,
Parla, Spain
| | - José Antonio Olmos
- Hospital Universitario Rey Juan Carlos, Gastroenterology,
Móstoles, Spain
| | - Laura López
- Hospital Universitari Sant Joan de Reus, Gastroenterology,
Reus, Spain
| | - Urko Aguirre
- Research Unit, Hospital de Galdakao. Red de Investigación en
Servicios de Salud en Enfermedades Crónicas (REDISSEC)
| | - Javier P. Gisbert
- Centro de Investigación Biomédica en Red de Enfermedades
Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Hospital Universitario de La Princesa, Gastroenterology, Madrid,
Spain
- Instituto de Investigación Sanitaria Princesa (IIS-IP),
Universidad Autónoma de Madrid (UAM), Madrid, Spain
| | - on behalf of the Young GETECCU Group
- Hospital de Galdakao, Gastroenterology, Galdakao, Spain
- Biocruces Bizkaia Health Research Institute, Barakaldo,
Spain
- Hospital Universitari i Politècnic de La Fe, Gastroenterology,
Valencia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades
Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Hospital Universitari i Politècnic de La Fe (Valencia),
Radiology, Valencia, Spain
- Hospital Universitario de La Princesa, Gastroenterology, Madrid,
Spain
- Instituto de Investigación Sanitaria Princesa (IIS-IP),
Universidad Autónoma de Madrid (UAM), Madrid, Spain
- Hospital Clinic, Gastroenterology, Barcelona, Spain
- Hospital Universitario Marqués de Valdecilla, Gastroenterology,
Santander, Spain
- Hospital Universitario Marqués de Valdecilla, Radiology,
Santander, Spain
- Hospital Clínico Universitario de Santiago de Compostela,
Gastroenterology, Santiago de Compostela, Spain
- Consorci Sanitari de Terrassa, Gastroenterology, Terrassa,
Spain
- Consorci Sanitari de Terrassa, Radiology, Terrassa, Spain
- Hospital Universitario La Paz, Gastroenterology, Madrid,
Spain
- Hospital del Mar, Gastroenterology, Barcelona, Spain, and
Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
- IIS Aragón, Hospital Clínico Universitario Lozano Blesa,
Gastroenterology, Zaragoza, Spain
- Complejo Asistencial Universitario de León, Gastroenterology,
León, Spain
- Hospital General de Granollers, Gastroenterology, Granollers,
Spain
- Hospital General de Granollers, Radiology, Granollers,
Spain
- Hospital Universitario de Fuenlabrada, Gastroenterology,
Fuenlabrada, Spain, and Instituto de Investigación de La Paz (IdiPaz), Madrid,
Spain
- Hospital Universitario de Fuenlabrada, Radiology, Fuenlabrada,
Spain
- Hospital Universitario de Cruces, Gastroenterology, Barakaldo,
Spain
- Hospital Ntra. Sra. Candelaria, Gastroenterology, Santa Cruz de
Tenerife, Spain
- Hospital Ntra. Sra. Candelaria, Radiology, Santa Cruz de
Tenerife, Spain
- Althaia, Xarxa Assistencial Universitària de Manresa,
Gastroenterology, Manresa, Spain
- Hospital Universitario Infanta Leonor, Gastroenterology,
Madrid, Spain
- Complejo Hospitalario Universitario de Ferrol,
Gastroenterology, Ferrol, Spain
- Hospital Universitario German Trias I Pujol, Gastroenterology,
Badalona, Spain
- Hospital Montecelo, Gastroenterology, Pontevedra, Spain
- Hospital de Montecelo, Radiology, Pontevedra, Spain
- Hospital Universitari Vall d'Hebron, Gastroenterology,
Barcelona, Spain
- Hospital San Agustín, Gastroenterology, Avilés, Spain
- Hospital Universitario Ramón y Cajal, Gastroenterology, Madrid,
Spain
- Hospital Santa Bárbara, Gastroenterology, Soria, Spain
- Hospital Universitario Reina Sofía, Gastroenterology, Córdoba,
Spain
- IMIBIC, Córdoba, Spain
- Hospital Puerta de Hierro, Gastroenterology, Madrid,
Spain
- Hospital Universitario Infanta Elena, Gastroenterology,
Valdemoro, Spain
- Osatek, Galdakao, Spain
- Hospital Royo Villanova, Gastroenterology, Zaragoza,
Spain
- Hospital Universitario del Henares, Gastroenterology, Coslada,
Spain
- Hospital Universitario del Henares, Radiology, Coslada,
Spain
- Hospital Universitario Infanta Cristina, Gastroenterology,
Parla, Spain
- Hospital Universitario Rey Juan Carlos, Gastroenterology,
Móstoles, Spain
- Hospital Universitari Sant Joan de Reus, Gastroenterology,
Reus, Spain
- Research Unit, Hospital de Galdakao. Red de Investigación en
Servicios de Salud en Enfermedades Crónicas (REDISSEC)
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Limsrivilai J, Aniwan S, Sudcharoen A, Chaisidhivej N, Prueksapanich P, Pausawasdi N, Charatcharoenwitthaya P, Pongprasobchai S, Manassatit S. Temporal trend of disease recognition, treatment paradigm, and clinical outcomes of Crohn disease in Thailand from 2000 through 2017: Is early use of thiopurines beneficial? Medicine (Baltimore) 2020; 99:e22216. [PMID: 32957358 PMCID: PMC7505316 DOI: 10.1097/md.0000000000022216] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
The prevalence of Crohn disease (CD) is increasing in Asia, but data from Southeast Asian population are scarce.The databases of 2 university-based national tertiary referral centers located in Bangkok, Thailand, were retrospectively reviewed for adult patients diagnosed with CD during January 2000 to December 2017. Disease characteristics, diagnosis, treatment, and outcomes were described and compared between the 2000 to 2009 cohort (cohort A) and the 2010 to 2017 cohort (cohort B).One hundred eighty-two patients (mean age: 46.4 years, 50% male) with 993 patient-years of follow-up were included. Thirteen percent had a history of intestinal resection, but were not diagnosed until disease recurrence. Another 6% were diagnosed at the time of first surgery. There was no improvement in diagnostic proficiency between cohorts. Mesalamine, corticosteroids, thiopurines, and biologics were prescribed in 75.8%, 81.3%, 84.6%, and 13.7% of patients, respectively (P > .05 between cohorts). Notably, thiopurines were started earlier in cohort B. Median time to the start of thiopurines was 6.2 and 1.65 months in cohort A and B, respectively (P < .01). However, the cumulative 5-year rates of disease behavior progression (P = .43), hospitalization (P = .14), and bowel surgery (P = .29) were not significantly different between cohorts. Subgroup analysis including only patients who required thiopurines showed the early use of thiopurines to be associated with lower risk of intestinal surgery after diagnosis (hazard ratio: 0.30, 95% confidence interval: 0.11-0.85).Early disease recognition and early introduction of immunomodulators may prevent long-term complications and reduce unnecessary surgery in CD.
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Affiliation(s)
- Julajak Limsrivilai
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Satimai Aniwan
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Asawin Sudcharoen
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Natapat Chaisidhivej
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Piyaphan Prueksapanich
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Nonthalee Pausawasdi
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Phunchai Charatcharoenwitthaya
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Supot Pongprasobchai
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Sathaporn Manassatit
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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44
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Rodríguez-Lago I, Zabana Y, Barreiro-de Acosta M. Diagnosis and natural history of preclinical and early inflammatory bowel disease. Ann Gastroenterol 2020; 33:443-452. [PMID: 32879589 PMCID: PMC7406806 DOI: 10.20524/aog.2020.0508] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 05/24/2020] [Indexed: 12/18/2022] Open
Abstract
Inflammatory bowel disease is a chronic and progressive disorder of the
gastrointestinal tract. A relevant proportion of patients develop complicated
lesions, defined as strictures, fistulas and/or abscesses already at diagnosis,
and this proportion increases over time. The preclinical phase defines the
period of time from the appearance of the first immune disturbances until the
development of overt disease, and it may be present months to years before the
diagnosis. Multiple biomarkers (e.g., C-reactive protein, interleukin-6, fecal
calprotectin) and cellular mechanisms (e.g., complement cascade, lysosomes,
innate immunity, and glycosaminoglycan metabolism) are already altered during
this period. Research in this area allows the description of the initial immune
disturbances that may identify potential targets and lead to the development of
new drug therapies. During this period, different interventions in high-risk
individuals, including drugs or environmental factors, will open the possibility
of innovative strategies focused on the reduction of complications, or even
prevention trials for inflammatory bowel disease. Here, we review the most
relevant findings regarding the characteristics, prevalence and biomarkers
associated with preclinical disease, along with their possible use in our future
clinical practice.
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Affiliation(s)
- Iago Rodríguez-Lago
- Gastroenterology Department, Hospital de Galdakao and Biocruces Bizkaia Health Research Institute, Galdakao (Iago Rodríguez-Lago)
| | - Yamile Zabana
- Gastroenterology Department, Hospital Universitari Mútua Terrassa, Terrassa (Yamile Zabana).,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) (Yamile Zabana)
| | - Manuel Barreiro-de Acosta
- Gastroenterology Department, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela (Manuel Barreiro-de Acosta), Spain
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45
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Cernoch PS, Fournier N, Zeitz J, Scharl M, Morell B, Greuter T, Schreiner P, Misselwitz B, Safroneeva E, Schoepfer AM, Vavricka SR, Rogler G, Biedermann L. Lower Risk of B1-to-pB3-Stage Migration in Crohn's Disease Upon Immunosuppressive and Anti-TNF Treatment in the Swiss IBD Cohort Study. Dig Dis Sci 2020; 65:2654-2663. [PMID: 31797187 DOI: 10.1007/s10620-019-05978-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2019] [Accepted: 11/27/2019] [Indexed: 12/22/2022]
Abstract
BACKGROUND While the long-term evolution of disease behavior in Crohn's disease has been well described in the pre-anti-TNF era, our knowledge thereon remains scarce after the introduction of anti-TNF. AIMS Our investigation examined the long-term evolution of disease concerning Montreal classification's B-stages over time in patients enrolled into the Swiss IBD Cohort Study between 2006 and 2017. METHODS We analyzed prospectively collected SIBDCS data using a Markov model and multivariate testing for effects of treatment and other confounders on B-stage migration over time. The primary outcome was a transition in disease behavior from B1 to either B2 or pB3, or from B2 to pB3, respectively. RESULTS The 10- and 15-year probability of remaining in B1 was 0.61 and 0.48, as opposed to a probability to migrate to B2 or B3 of 0.25 or 0.14, and 0.32 or 0.2, after 10 and 15 years, respectively. In multivariate testing, the hazard ratio for migrating from B1 to pB3 (HR 0.27) and from B2 to pB3 (HR 0.12) was lower in patients > 40 years compared to patients < 17 years. We found that immunosuppression (HR 0.38) and treatment with anti-TNF for > 1 year (HR 0.30) were associated with a decreased likelihood of transitioning from stage B1 to pB3. CONCLUSIONS While in the anti-TNF era most patients with Crohn's disease will eventually develop stricturing and/or penetrating complications, our data indicate that immunosuppressive and anti-TNF treatment for more than 1 year reduce the risk of transitioning from stage B1 to pB3 in the long-term run.
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Affiliation(s)
- Patrick S Cernoch
- Division of Gastroenterology and Hepatology, Department of Gastroenterology, University Hospital Zurich (USZ), University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.
| | - Nicolas Fournier
- Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Biopôle 2, Route de la Corniche 10, 1010, Lausanne, Switzerland
| | - Jonas Zeitz
- Division of Gastroenterology and Hepatology, Department of Gastroenterology, University Hospital Zurich (USZ), University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.,Center of Gastroenterology, Clinic Hirslanden, Witellikerstrasse 40, 8032, Zurich, Switzerland
| | - Michael Scharl
- Division of Gastroenterology and Hepatology, Department of Gastroenterology, University Hospital Zurich (USZ), University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
| | - Bernhard Morell
- Division of Gastroenterology and Hepatology, Department of Gastroenterology, University Hospital Zurich (USZ), University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
| | - Thomas Greuter
- Division of Gastroenterology and Hepatology, Department of Gastroenterology, University Hospital Zurich (USZ), University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
| | - Philipp Schreiner
- Division of Gastroenterology and Hepatology, Department of Gastroenterology, University Hospital Zurich (USZ), University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
| | - Benjamin Misselwitz
- Division of Gastroenterology and Hepatology, Department of Gastroenterology, University Hospital Zurich (USZ), University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
| | - Ekaterina Safroneeva
- Institute of Social and Preventive Medicine, University of Bern, Finkenhubelweg 11, 3012, Bern, Switzerland
| | - Alain M Schoepfer
- Division of Gastroenterology and Hepatology, Center Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, Rue du Bugnon 46, 1010, Lausanne, Switzerland
| | - Stephan R Vavricka
- Division of Gastroenterology and Hepatology, Department of Gastroenterology, University Hospital Zurich (USZ), University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.,Center of Gastroenterology and Hepatology, Vulkanplatz 8, 8048, Zurich, Switzerland
| | - Gerhard Rogler
- Division of Gastroenterology and Hepatology, Department of Gastroenterology, University Hospital Zurich (USZ), University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
| | - Luc Biedermann
- Division of Gastroenterology and Hepatology, Department of Gastroenterology, University Hospital Zurich (USZ), University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
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46
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Jung YS, Han M, Park S, Cheon JH. Impact of early anti-TNF use on clinical outcomes in Crohn's disease: a nationwide population-based study. Korean J Intern Med 2020; 35:1104-1113. [PMID: 32306709 PMCID: PMC7487310 DOI: 10.3904/kjim.2020.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Revised: 03/06/2020] [Accepted: 03/17/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND/AIMS The optimal timing for initiation of anti-tumor necrosis factor (TNF) therapy in Crohn's disease (CD) is still debated. Little is known about the clinical outcomes of early versus late administration of anti-TNF agents, especially in Asian CD patients. We aimed to evaluate the impact of early anti-TNF therapy on clinical outcomes in Korean CD patients. METHODS Using the Korean National Health Insurance Claims database, we collected data on patients diagnosed with CD who received anti-TNF therapy for more than 6 months between 2010 and 2016. Early initiation of anti-TNF therapy was defined as those starting infliximab or adalimumab therapy within 1 year of diagnosis. The following outcomes were assessed using a Cox proportional hazard model: abdominal surgery, CD-related emergency room (ER) visit, CD-related hospitalization, and new corticosteroid use. RESULTS Among 1,207 patients, 609 were early initiators of anti-TNF. Late anti-TNF initiation (> 1 year after diagnosis) was associated with increased risk of surgery (adjusted hazard ratio [aHR], 1.64; 95% confidence interval [CI], 1.05 to 2.55) and tended to be associated with increased risk of ER visit (aHR, 1.38; 95% CI, 0.99 to 1.94). However, there were no significant differences in the risk of hospitalization and corticosteroid use between early and late initiators. CONCLUSION Early anti-TNF therapy among Korean CD patients within 1 year of diagnosis was associated with better clinical outcomes than late therapy, such as lower surgery and ER visit rates. Our results suggest that aggressive medical intervention in the early stages of CD may potentially change the course of this disease.
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Affiliation(s)
- Yoon Suk Jung
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Minkyung Han
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Korea
| | - Sohee Park
- Department of Biostatistics, Yonsei University Graduate School of Public Health, Seoul, Korea
| | - Jae Hee Cheon
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
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47
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Early Intervention in Ulcerative Colitis: Ready for Prime Time? J Clin Med 2020; 9:jcm9082646. [PMID: 32823997 PMCID: PMC7464940 DOI: 10.3390/jcm9082646] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2020] [Revised: 08/09/2020] [Accepted: 08/12/2020] [Indexed: 12/15/2022] Open
Abstract
Growing evidence shows that ulcerative colitis (UC) is a progressive disease similar to Crohn’s disease (CD). The UC-related burden is often underestimated by physicians and a standard step-up therapeutic approach is preferred. However, in many patients with UC the disease activity is not adequately controlled by current management, leading to poor long-term prognosis. Data from both randomized controlled trials and real-world studies support early intervention in CD in order to prevent disease progression and irreversible bowel damage. Similarly, an early disease intervention during the so-called “window of opportunity” could lead to better outcomes in UC. Here, we summarize the literature evidence on early intervention in patients with UC, highlighting strengths and limitations of this approach.
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48
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Walker GJ, Lin S, Chanchlani N, Thomas A, Hendy P, Heerasing N, Moore L, Green HD, Chee D, Bewshea C, Mays J, Kennedy NA, Ahmad T, Goodhand JR. Quality improvement project identifies factors associated with delay in IBD diagnosis. Aliment Pharmacol Ther 2020; 52:471-480. [PMID: 32573819 DOI: 10.1111/apt.15885] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 02/23/2020] [Accepted: 05/24/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Delay in the diagnosis of inflammatory bowel disease (IBD) is common and contemporary UK studies are lacking. AIM To determine factors associated with, and the consequences of, a prolonged time to diagnosis in IBD. METHODS This quality improvement study included 304 adults with a new IBD diagnosis made between January 2014 and December 2017 across 49 general practices (GP) and gastroenterology secondary care services. Outcome measures were demographic, clinical and laboratory factors associated with a delayed time, defined as greater than upper quartile, to: (a) patient presentation (b) GP referral (c) secondary care diagnosis, and factors associated with a complicated disease course (hospitalisation and/or surgery and/or biologic treatment) in the year after diagnosis. RESULTS The median [IQR] diagnosis sub-intervals were: (a) patient = 2.1 months [0.9-5.1]; (b) GP = 0.3 months [0.0-0.9]; (c) secondary care = 1.1 months [0.5-2.1]. 50% of patients were diagnosed within 4 months and 92% were diagnosed within 2 years of symptom onset. Diagnostic delay was more common in Crohn's disease (7.6 months [3.1-15.0]) than ulcerative colitis (3.3 months [1.9-7.3]) (P < 0.001). Patients who presented as an emergency (P < 0.001) but not those with a delayed overall time to diagnosis (P = 0.35) were more likely to have a complicated disease course. CONCLUSION Time to patient presentation is the largest component of time to IBD diagnosis. Emergency presentation is common and, unlike a delayed time to diagnosis, is associated with a complicated disease course.
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Affiliation(s)
- Gareth J Walker
- Exeter IBD and Pharmacogenetics Research Group, Exeter, UK
- Department of Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | - Simeng Lin
- Exeter IBD and Pharmacogenetics Research Group, Exeter, UK
- Department of Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | | | - Amanda Thomas
- Exeter IBD and Pharmacogenetics Research Group, Exeter, UK
- Department of Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | - Peter Hendy
- Exeter IBD and Pharmacogenetics Research Group, Exeter, UK
- Department of Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | - Neel Heerasing
- Exeter IBD and Pharmacogenetics Research Group, Exeter, UK
- Department of Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | - Lucy Moore
- Exeter IBD and Pharmacogenetics Research Group, Exeter, UK
| | - Harry D Green
- Exeter IBD and Pharmacogenetics Research Group, Exeter, UK
| | - Desmond Chee
- Exeter IBD and Pharmacogenetics Research Group, Exeter, UK
- Department of Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | - Claire Bewshea
- Exeter IBD and Pharmacogenetics Research Group, Exeter, UK
| | - Joseph Mays
- NHS Devon Clinical Commissioning Group, Exeter, UK
| | - Nicholas A Kennedy
- Exeter IBD and Pharmacogenetics Research Group, Exeter, UK
- Department of Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | - Tariq Ahmad
- Exeter IBD and Pharmacogenetics Research Group, Exeter, UK
- Department of Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | - James R Goodhand
- Exeter IBD and Pharmacogenetics Research Group, Exeter, UK
- Department of Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
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Dulai PS, Peyrin-Biroulet L, Demuth D, Lasch K, Hahn KA, Lindner D, Patel H, Jairath V. Early Intervention With Vedolizumab on Longer Term Surgery Rates in Crohn's Disease: Post Hoc Analysis of the GEMINI Phase 3 and Long-term Safety Programs. J Crohns Colitis 2020; 15:jjaa153. [PMID: 32691844 PMCID: PMC7904078 DOI: 10.1093/ecco-jcc/jjaa153] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Indexed: 12/24/2022]
Abstract
BACKGROUND Crohn's disease (CD) is a chronic inflammatory bowel disease that, with progression, may require surgical intervention. AIM To determine whether vedolizumab treatment of CD earlier in the disease course (≤2 or ≤5 years disease duration) influences risk of CD-related surgery after accounting for probability of response. METHODS Post hoc analyses of data from CD patients treated with vedolizumab in the GEMINI 2, GEMINI 3, and GEMINI LTS trials (N=1253) evaluated CD-related surgery (bowel resection or colectomy) with stratification by probability of response to vedolizumab (low/intermediate or high). Analyses used a previously validated clinical decision support tool and both logistic regression and Cox proportional hazard analyses. RESULTS In total, 113 (9.0%) vedolizumab-treated patients required CD-related surgery. Surgical rates were 6.1% and 9.8% for the high and low/intermediate probability of response groups, respectively. Risk of surgery was lower for patients with a high probability of response versus those with a low/intermediate probability of response (HR 0.50; 95%CI 0.29 to 0.85). For patients with a low/intermediate probability of vedolizumab response, there was a consistent trend for association between earlier treatment (≤2 or ≤5 years since diagnosis) and a lower risk of surgery relative to later treatment (≤2 years versus >2 years: OR 0.77, 95%CI 0.38 to 1.58; ≤5 years versus >5 years: OR 0.61, 95%CI 0.37 to 1.00). CONCLUSIONS Earlier intervention with vedolizumab may be associated with lower rates of surgery. Use of the clinical decision support tool may help identify patients most likely to benefit from earlier intervention with vedolizumab.
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Affiliation(s)
- Parambir S Dulai
- Division of Gastroenterology, University of California – San Diego, La Jolla, CA, USA
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, Vandoeuvre-les-Nancy, France; Inserm U1256 NGERE, Lorraine University, Vandoeuvre-les-Nancy, France
| | - Dirk Demuth
- GEM Medical Affairs, Takeda Pharmaceuticals International—Singapore
| | - Karen Lasch
- US Medical Affairs, Takeda Pharmaceuticals USA, Inc., Deerfield, IL, USA
| | | | - Dirk Lindner
- Statistical and Quantitative Sciences, Takeda Pharmaceuticals International AG, Zurich, Switzerland
| | - Haridarshan Patel
- Global Medical Affairs, Takeda Pharmaceuticals USA, Inc., Deerfield, IL, USA
- Current affiliation: Immensity Consulting, Inc., Chicago, IL, USA
| | - Vipul Jairath
- Department of Medicine, Division of Gastroenterology, Western University, London, ON, Canada
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50
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Blackwell J, Saxena S, Jayasooriya N, Bottle A, Petersen I, Hotopf M, Alexakis C, Pollok RC. Prevalence and duration of gastrointestinal symptoms before diagnosis of Inflammatory Bowel Disease and predictors of timely specialist review: a population-based study. J Crohns Colitis 2020; 15:jjaa146. [PMID: 32667962 DOI: 10.1093/ecco-jcc/jjaa146] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Lack of timely referral and significant waits for specialist review amongst individuals with unresolved gastrointestinal (GI) symptoms can result in delayed diagnosis of Inflammatory Bowel Disease (IBD). AIMS To determine the frequency and duration of GI symptoms and predictors of timely specialist review before the diagnosis of both Crohn's Disease (CD) and ulcerative colitis (UC). METHODS Case-control study of IBD matched 1:4 for age and sex to controls without IBD using the Clinical Practice Research Datalink from 1998-2016. RESULTS We identified 19,555 cases of IBD, and 78,114 controls. 1 in 4 cases of IBD reported gastrointestinal symptoms to their primary care physician more than 6 months before receiving a diagnosis. There is a significant excess prevalence of GI symptoms in each of the 10 years before IBD diagnosis. GI symptoms were reported by 9.6% and 10.4% at 5 years before CD and UC diagnosis respectively compared to 5.8% of controls. Amongst patients later diagnosed with IBD, <50% received specialist review within 18 months from presenting with chronic GI symptoms. Patients with a previous diagnosis of irritable bowel syndrome or depression were less likely to receive timely specialist review (IBS: HR=0.77, 95%CI 0.60-0.99, depression: HR=0.77, 95%CI 0.60-0.98). CONCLUSIONS There is an excess of GI symptoms 5 years before diagnosis of IBD compared to the background population which are likely attributable to undiagnosed disease. Previous diagnoses of IBS and depression are associated with delays in specialist review. Enhanced pathways are needed to accelerate specialist referral and timely IBD diagnosis.
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Affiliation(s)
- J Blackwell
- Dept. Gastroenterology, St George's Healthcare NHS Trust, St George's University London, UK
| | - S Saxena
- School of Public Health, Imperial College London, London, UK
| | - N Jayasooriya
- Dept. Gastroenterology, St George's Healthcare NHS Trust, St George's University London, UK
| | - A Bottle
- School of Public Health, Imperial College London, London, UK
| | - I Petersen
- Dept. Primary Care and Population Health, University College London, London, UK
- Dept. Clinical Epidemiology, Aarhus University, Denmark
| | - M Hotopf
- Institute of Psychiatry, Kings College London, London, UK
- South London and Maudsley NHS Foundation Trust, London, UK
| | - C Alexakis
- Dept. Gastroenterology, St George's Healthcare NHS Trust, St George's University London, UK
| | - R C Pollok
- Dept. Gastroenterology, St George's Healthcare NHS Trust, St George's University London, UK
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