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Nardone OM, Calabrese G, Barberio B, Giglio MC, Castiglione F, Luglio G, Savarino E, Ghosh S, Iacucci M. Rates of Endoscopic Recurrence In Postoperative Crohn's Disease Based on Anastomotic Techniques: A Systematic Review And Meta-Analysis. Inflamm Bowel Dis 2024; 30:1877-1887. [PMID: 37931290 DOI: 10.1093/ibd/izad252] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Indexed: 11/08/2023]
Abstract
BACKGROUND Patients with Crohn's disease (CD) after ileocolic resection may develop an endoscopic postoperative recurrence (ePOR) that reaches 40% to 70% of incidence within 6 months. Recently, there has been growing interest in the potential effect of anastomotic configurations on ePOR. Kono-S anastomosis has been proposed for reducing the risk of clinical and ePOR. Most studies have assessed the association of ileocolonic anastomosis and ePOR individually, while there is currently limited data simultaneously comparing several types of anastomosis. Therefore, we performed a systematic review and meta-analysis to assess the impact of different ileocolonic anastomosis on ePOR in CD. METHODS We searched PubMed and Embase from inception to January 2023 for eligible studies reporting the types of anastomoses and, based on these, the rate of endoscopic recurrence at ≥6 months. Studies were grouped by conventional anastomosis, including side-to-side, end-to-end, and end-to-side vs Kono-S, and comparisons were made between these groups. Pooled incidence rates of ePOR were computed using random-effect modelling. RESULTS Seventeen studies, with 2087 patients who underwent ileocolic resection for CD were included. Among these patients, 369 (17,7%) Kono-S anastomoses were performed, while 1690 (81,0%) were conventional ileocolic anastomosis. Endoscopic postoperative recurrence at ≥6 months showed a pooled incidence of 37.2% (95% CI, 27.7-47.2) with significant heterogeneity among the studies (P < .0001). In detail, patients receiving a Kono-S anastomosis had a pooled incidence of ePOR of 24.7% (95% CI, 6.8%-49.4%), while patients receiving a conventional anastomosis had an ePOR of 42.6% (95% CI, 32.2%-53.4%). CONCLUSIONS Kono-S ileocolic anastomosis was more likely to decrease the risk of ePOR at ≥6 months compared with conventional anastomosis. Our findings highlight the need to implement the use of Kono-S anastomosis, particularly for difficult to treat patients. However, results from larger randomized controlled trials are needed to confirm these data.
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Affiliation(s)
- Olga Maria Nardone
- Gastroenterology, Department of Public Health, School of Medicine, Federico II University of Naples, Naples, Italy
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Giulio Calabrese
- Gastroenterology, Department of Clinical Medicine and Surgery, School of Medicine, Federico II University of Naples, Naples, Italy
| | - Brigida Barberio
- Division of Gastroenterology, Department of Surgery Oncology and Gastroenterology DiSCOG, University of Padova, Padova, Italy
| | - Mariano Cesare Giglio
- Gastroenterology, Department of Clinical Medicine and Surgery, School of Medicine, Federico II University of Naples, Naples, Italy
| | - Fabiana Castiglione
- Gastroenterology, Department of Clinical Medicine and Surgery, School of Medicine, Federico II University of Naples, Naples, Italy
| | - Gaetano Luglio
- Department of Public Health, Endoscopic Surgery Unit, School of Medicine, University of Naples Federico II, Naples, Italy
| | - Edoardo Savarino
- Division of Gastroenterology, Department of Surgery Oncology and Gastroenterology DiSCOG, University of Padova, Padova, Italy
| | - Subrata Ghosh
- APC Microbiome Ireland, College of Medicine and Health, University College Cork, College Road, National University of Ireland, T12 K8AF Cork, Ireland
| | - Marietta Iacucci
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
- APC Microbiome Ireland, College of Medicine and Health, University College Cork, College Road, National University of Ireland, T12 K8AF Cork, Ireland
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Moskow J, Thurston T, Saleh A, Shah A, Abraham BP, Glassner K. Postoperative Ustekinumab Drug Levels and Disease Activity in Patients with Crohn's Disease. Dig Dis Sci 2024; 69:2944-2954. [PMID: 38789673 DOI: 10.1007/s10620-024-08471-0] [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: 01/05/2024] [Accepted: 04/30/2024] [Indexed: 05/26/2024]
Abstract
AIMS This study investigated how post-operative ustekinumab levels relate to surgery type, endoscopic, biochemical, and clinical outcomes in patients with Crohn's Disease. METHODS A retrospective study of patients with Crohn's Disease with a disease-related operation between 2016 and 2022 assessed outcomes based on ustekinumab levels. Patients were included if they had an ustekinumab trough level within two years post-operatively. Patients were separated into groups based on whether their ustekinumab trough levels were adequate, defined as ≥ 4 μg/mL, or suboptimal < 4 μg/mL. A subset of patients with ustekinumab levels taken within two years both before and after surgery was compared to non-surgical treatment-escalated controls outside the initial patient set. Harvey-Bradshaw index was used to evaluate clinical disease activity. Rutgeert's and Simple Endoscopic Score for Crohn's Disease was used to evaluate endoscopic disease activity. C-reactive protein and fecal calprotectin values were collected to evaluate the molecular inflammatory disease state. CBC data were used to evaluate anemia. RESULTS Forty-four patients were identified, which had ustekinumab levels after Crohn's Disease-related surgery. Twelve of these patients had pre-operative levels and were compared to 26 non-surgical treatment-escalated controls. No relationship between ustekinumab levels and endoscopic or clinical disease activity post-operatively was found. This also held true when looking at different surgery types. Adequate levels of ustekinumab post-operatively yielded lower risk of anemia. Surgery itself did not have an impact on ustekinumab levels. CONCLUSIONS This study provided new insights into how post-operative ustekinumab levels impact several factors in patients having undergone Crohn's disease-related surgery.
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Affiliation(s)
- Joshua Moskow
- Engineering Medicine, Texas A&M Health Science Center, 1020 Holcombe Blvd, Houston, TX, 77030, USA
| | - Theresa Thurston
- Engineering Medicine, Texas A&M Health Science Center, 1020 Holcombe Blvd, Houston, TX, 77030, USA
| | - Adam Saleh
- Engineering Medicine, Texas A&M Health Science Center, 1020 Holcombe Blvd, Houston, TX, 77030, USA
| | - Ayushi Shah
- Division of Gastroenterology, SUNY Upstate Medical University, Syracuse, NY, 13210, USA
| | - Bincy P Abraham
- Division of Gastroenterology and Hepatology, Department of Medicine, Lynda K and David M Underwood Center for Digestive Disorders, Houston Methodist Hospital, 6550 Fannin St Ste 1201, Houston, TX, 77030, USA
- Weill Cornell Medicine, New York, NY, USA
| | - Kerri Glassner
- Division of Gastroenterology and Hepatology, Department of Medicine, Lynda K and David M Underwood Center for Digestive Disorders, Houston Methodist Hospital, 6550 Fannin St Ste 1201, Houston, TX, 77030, USA.
- Weill Cornell Medicine, New York, NY, USA.
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Gisbert JP, Chaparro M. Anti-TNF Agents and New Biological Agents (Vedolizumab and Ustekinumab) in the Prevention and Treatment of Postoperative Recurrence After Surgery in Crohn's Disease. Drugs 2023; 83:1179-1205. [PMID: 37505446 PMCID: PMC10462742 DOI: 10.1007/s40265-023-01916-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/21/2023] [Indexed: 07/29/2023]
Abstract
Surgery for Crohn's disease (CD) is not curative, as postoperative recurrence (POR) after ileocolonic resection is the rule in the absence of prophylactic treatment. In the present article, we critically review available data on the role of anti-tumour necrosis factor (TNF) agents and new biologics (including vedolizumab and ustekinumab) in the prevention and treatment of POR after surgery in CD. Several studies (summarised in various meta-analyses) have confirmed the efficacy of anti-TNFs in the prevention of POR. We identified 37 studies, including 1863 CD patients, with mean endoscopic POR at 6-12 months of 29%. Only few randomised controlled trials (RCTs) have directly compared thiopurines and anti-TNFs, with controversial results, although the superiority of the latter is supported by several meta-analyses. Infliximab and adalimumab seem equally effective. The combination of anti-TNFs and immunosuppressives should be considered in patients previously exposed to anti-TNFs. Several studies have shown that anti-TNFs remain an effective option to prevent POR also in patients with anti-TNF failure before surgery. In fact, the use of the same anti-TNF before and after surgery might be effective for the prevention of POR. Prophylactic anti-TNF treatment, once started, should be continued long term. Anti-TNFs are also effective for the treatment of established POR. Retreatment with anti-TNFs for POR is a valid strategy even after their preoperative failure. In six studies (including 156 patients) evaluating vedolizumab, mean endoscopic POR at 6-12 months was 41%. The non-randomised comparison of anti-TNFs and vedolizumab has provided controversial results. One placebo-controlled RCT confirmed that vedolizumab is quite effective in preventing POR in CD patients with increased risk of recurrence. Seven studies (including 162 patients) evaluated ustekinumab, with a mean endoscopic POR at 6-12 months of 41%. The comparative efficacy of ustekinumab and anti-TNFs is still unclear. Ustekinumab and vedolizumab seem to be equally effective, although the experience is very limited. In conclusion, to date, anti-TNFs are the most effective agents in preventing and treating POR in CD. Anti-TNFs remain an effective option to prevent POR also in patients with anti-TNF failure before surgery. Vedolizumab seems to be quite effective in the prevention of POR in patients with increased risk of recurrence. Ustekinumab is probably also effective in the postoperative setting, although the comparative efficacy with anti-TNFs or vedolizumab is still unclear.
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Affiliation(s)
- Javier P Gisbert
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Diego de León, 62, 28006, Madrid, Spain.
| | - María Chaparro
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Diego de León, 62, 28006, Madrid, Spain
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Pan Y, Ahmed W, Mahtani P, Wong R, Longman R, Jeremy Lukin D, Scherl EJ, Battat R. Utility of Therapeutic Drug Monitoring for Tumor Necrosis Factor Antagonists and Ustekinumab in Postoperative Crohn's Disease. Inflamm Bowel Dis 2022; 28:1865-1871. [PMID: 35212368 DOI: 10.1093/ibd/izac030] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Indexed: 12/29/2022]
Abstract
BACKGROUND In postoperative Crohn's disease (POCD), data are lacking on relationships between serum biologic concentrations and treatment outcomes. We assessed if established threshold concentrations of infliximab (IFX), adalimumab (ADA), and ustekinumab (UST) impact outcomes in POCD. METHODS Data were extracted from POCD patients with serum biologic concentration measurements using Weill Cornell Medicine biobanks. The primary outcome compared rates of deep remission (achieving both objective [endoscopic or biomarker] and clinical [Harvey-Bradshaw index or Crohn's Disease Patient Reported Outcome-2] remission), using established serum drug level cutoffs of IFX ≥3 µg/mL, ADA ≥7.5 µg/mL, and UST ≥4.5 µg/mL. RESULTS In 130 patients, median IFX, ADA, and UST concentrations were 10 (interquartile range [IQR], 2.9-26.9) µg/mL, 10.5 (IQR, 4.9-14.9) µg/mL, and 6.9 (IQR, 5.1-10.2) µg/mL, respectively. In patients with IFX ≥3 µg/mL, higher rates of deep remission (39% vs 0%; P = .02) existed compared with those with IFX <3 µg/mL. Similar differences existed for clinical (44% vs 9%; P = .04) and objective (83% vs 62%; P = .1) remission. In patients with ADA ≥7.5 µg/mL, rates of deep (42% vs 0%; P = .02), clinical (42% vs 0%; P = .02), and objective (88% vs 40%; P = .007) remission were higher than patients with lower concentrations. For UST, rates of deep (28% vs 17%; P = 1.0), clinical (33% vs 33%; P = 1.0), and objective (70% vs 67%; P = 1.0) remission were similar between patients regardless of drug concentration. CONCLUSIONS In POCD, established anti-tumor necrosis factor concentrations were associated with improved outcomes. No relationship between UST concentrations and postoperative outcomes existed.
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Affiliation(s)
- Yushan Pan
- Joan & Sanford I. Weill Medical College of Cornell University, New York, NY, USA
| | - Waseem Ahmed
- Crohn's and Colitis Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Prerna Mahtani
- Jill Roberts Center for Inflammatory Bowel Disease, NewYork-Presbyterian/Weill Cornell Medicine, New York, NY, USA
| | - Rochelle Wong
- Department of Medicine, NewYork-Presbyterian/Weill Cornell Medicine, New York, NY, USA
| | - Randy Longman
- Jill Roberts Center for Inflammatory Bowel Disease, NewYork-Presbyterian/Weill Cornell Medicine, New York, NY, USA
| | - Dana Jeremy Lukin
- Jill Roberts Center for Inflammatory Bowel Disease, NewYork-Presbyterian/Weill Cornell Medicine, New York, NY, USA
| | - Ellen J Scherl
- Jill Roberts Center for Inflammatory Bowel Disease, NewYork-Presbyterian/Weill Cornell Medicine, New York, NY, USA
| | - Robert Battat
- Jill Roberts Center for Inflammatory Bowel Disease, NewYork-Presbyterian/Weill Cornell Medicine, New York, NY, USA
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Grossberg LB, Cheifetz AS, Papamichael K. Therapeutic Drug Monitoring of Biologics in Crohn's Disease. Gastroenterol Clin North Am 2022; 51:299-317. [PMID: 35595416 DOI: 10.1016/j.gtc.2021.12.007] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/17/2023]
Abstract
Reactive therapeutic drug monitoring (TDM) is considered the standard of care for optimizing biologics in inflammatory bowel disease (IBD) including Crohn's disease (CD). Preliminary data show that proactive TDM is associated with positive outcomes in IBD and can be also used to efficiently guide therapeutic decisions in specific clinical scenarios. Higher biological drug concentrations are associated with favorable therapeutic outcomes in specific IBD populations or phenotypes including pediatric CD, perianal fistulizing CD, small bowel CD, and following an ileocolonic resection for CD. Future perspectives of TDM include the use of rapid testing, pharmacogenomics, and pharmacokinetic dashboards toward individualized therapy.
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Affiliation(s)
- Laurie B Grossberg
- Division of Gastroenterology, Center for Inflammatory Bowel Diseases, Beth-Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA.
| | - Adam S Cheifetz
- Division of Gastroenterology, Center for Inflammatory Bowel Diseases, Beth-Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA
| | - Konstantinos Papamichael
- Division of Gastroenterology, Center for Inflammatory Bowel Diseases, Beth-Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA
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Papamichael K, Afif W, Drobne D, Dubinsky MC, Ferrante M, Irving PM, Kamperidis N, Kobayashi T, Kotze PG, Lambert J, Noor NM, Roblin X, Roda G, Vande Casteele N, Yarur AJ, Arebi N, Danese S, Paul S, Sandborn WJ, Vermeire S, Cheifetz AS, Peyrin-Biroulet L. Therapeutic drug monitoring of biologics in inflammatory bowel disease: unmet needs and future perspectives. Lancet Gastroenterol Hepatol 2022; 7:171-185. [PMID: 35026171 PMCID: PMC10187071 DOI: 10.1016/s2468-1253(21)00223-5] [Citation(s) in RCA: 83] [Impact Index Per Article: 27.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 06/14/2021] [Accepted: 06/15/2021] [Indexed: 01/05/2023]
Abstract
Therapeutic drug monitoring (TDM) has emerged as a useful tool for optimising the use of biologics, and in particular anti-tumour necrosis factor (anti-TNF) therapy, in inflammatory bowel disease (IBD). However, challenges remain and are hindering the widespread implementation of TDM in clinical practice. These barriers include identification of the optimal drug concentration to target, the lag time between sampling and results, and the proper interpretation of anti-drug antibody titres among different assays. Solutions to overcome these barriers include the harmonisation of TDM assays and the use of point-of-care testing. Other unmet needs include well designed prospective studies and randomised controlled trials focusing on proactive TDM, particularly during induction therapy. Future studies should also investigate the utility of TDM for biologics other than anti-TNF therapies in both IBD and other immune-mediated inflammatory diseases such as rheumatoid arthritis and psoriasis, and the use of pharmacokinetic modelling dashboards and pharmacogenetics towards individual personalised medicine.
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Affiliation(s)
- Konstantinos Papamichael
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
| | - Waqqas Afif
- Department of Medicine, Division of Gastroenterology, McGill University Health Center, Montreal, QC, Canada
| | - David Drobne
- Department of Gastroenterology, University Medical Centre Ljubljana, Ljubljana, Slovenia; Medical Faculty, University of Ljubljana, Ljubljana, Slovenia
| | - Marla C Dubinsky
- Department of Pediatrics, Susan and Leonard Feinstein IBD Clinical Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Marc Ferrante
- KU Leuven, Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Peter M Irving
- Gastroenterology, Guy's and St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | | | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Paulo G Kotze
- Catholic University of Paraná (PUCPR), Curitiba, Brazil
| | - Jo Lambert
- Department of Head and Skin, Ghent University Hospital, Ghent, Belgium
| | - Nurulamin M Noor
- Department of Gastroenterology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Xavier Roblin
- Department of Gastroenterology, University Hospital of Saint Etienne, Saint Etienne, France
| | - Giulia Roda
- IBD Center, Humanitas Clinical and Research Center-IRCCS, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | | | | | - Naila Arebi
- Department of IBD, St Mark's Hospital, Imperial College London, London, UK
| | - Silvio Danese
- IBD Center, Humanitas Clinical and Research Center-IRCCS, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Stephane Paul
- Department of Gastroenterology, University Hospital of Saint Etienne, Saint Etienne, France
| | - William J Sandborn
- Department of Medicine, University of California San Diego, La Jolla, CA, USA
| | - Séverine Vermeire
- KU Leuven, Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Adam S Cheifetz
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, Nancy, France; INSERM U1256 NGERE, Lorraine University, Nancy, France
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Nones RB, Fleshner PR, Queiroz NSF, Cheifetz AS, Spinelli A, Danese S, Peyrin-Biroulet L, Papamichael K, Kotze PG. Therapeutic Drug Monitoring of Biologics in IBD: Essentials for the Surgical Patient. J Clin Med 2021; 10:jcm10235642. [PMID: 34884344 PMCID: PMC8658146 DOI: 10.3390/jcm10235642] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 11/22/2021] [Accepted: 11/24/2021] [Indexed: 12/11/2022] Open
Abstract
Despite significant development in the pharmacological treatment of inflammatory bowel diseases (IBD) along with the evolution of therapeutic targets and treatment strategies, a significant subset of patients still requires surgery during the course of the disease. As IBD patients are frequently exposed to biologics at the time of abdominal and perianal surgery, it is crucial to identify any potential impact of biological agents in the perioperative period. Even though detectable serum concentrations of biologics do not seem to increase postoperative complications after abdominal procedures in IBD, there is increasing evidence on the role of therapeutic drug monitoring (TDM) in the perioperative setting. This review aims to provide a comprehensive summary of published studies reporting the association of drug concentrations and postoperative outcomes, postoperative recurrence (POR) after an ileocolonic resection for Crohn’s disease (CD), colectomy rates in ulcerative colitis (UC), and perianal fistulizing CD outcomes in patients treated with biologics. Current data suggest that serum concentrations of biologics are not associated with an increased risk in postoperative complications following abdominal procedures in IBD. Moreover, higher concentrations of anti-TNF agents are associated with a reduction in colectomy rates in UC. Finally, higher serum drug concentrations are associated with reduced rates of POR after ileocolonic resections and increased rates of perianal fistula healing in CD. TDM is being increasingly used to guide clinical decision making with favorable outcomes in many clinical scenarios. However, given the lack of high quality data deriving mostly from retrospective studies, the evidence supporting the systematic application of TDM in the perioperative setting is still inconclusive.
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Affiliation(s)
- Rodrigo Bremer Nones
- Health Sciences Postgraduate Program, School of Medicine, Pontifical Catholic University of Paraná (PUCPR), Curitiba 80215-901, Brazil;
| | - Phillip R. Fleshner
- Division of Colon and Rectal Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA;
| | | | - Adam S. Cheifetz
- Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (A.S.C.); (K.P.)
| | - Antonino Spinelli
- Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Milan, Italy;
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Milan, Italy;
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Milan, Italy;
- IBD Centre, Humanitas Research Hospital, 20089 Milan, Italy
| | | | - Konstantinos Papamichael
- Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (A.S.C.); (K.P.)
| | - Paulo Gustavo Kotze
- Health Sciences Postgraduate Program, School of Medicine, Pontifical Catholic University of Paraná (PUCPR), Curitiba 80215-901, Brazil;
- IBD Outpatient Clinics, Pontifical Catholic University of Paraná (PUCPR), Curitiba 80215-901, Brazil
- Correspondence:
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Iheozor‐Ejiofor Z, Gordon M, Clegg A, Freeman SC, Gjuladin‐Hellon T, MacDonald JK, Akobeng AK. Interventions for maintenance of surgically induced remission in Crohn's disease: a network meta-analysis. Cochrane Database Syst Rev 2019; 9:CD013210. [PMID: 31513295 PMCID: PMC6741529 DOI: 10.1002/14651858.cd013210.pub2] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND Crohn's disease (CD) is a chronic disease of the gut. About 75% of people with CD undergo surgery at least once in their lifetime to induce remission. However, as there is no known cure for the disease, patients usually experience a recurrence even after surgery. Different interventions are routinely used in maintaining postsurgical remission. There is currently no consensus on which treatment is the most effective. OBJECTIVES To assess the effects and harms of interventions for the maintenance of surgically induced remission in Crohn's disease and rank the treatments in order of effectiveness. SEARCH METHODS We searched the Cochrane IBD Group Specialized Register, CENTRAL, MEDLINE, and Embase from inception to 15 January 2019. We also searched reference lists of relevant articles, abstracts from major gastroenterology meetings, ClinicalTrials.gov, and the WHO ICTRP. There was no restriction on language, date, or publication status. SELECTION CRITERIA We considered for inclusion randomised controlled trials (RCTs) that compared different interventions used for maintaining surgically induced remission in people with CD who were in postsurgical remission. Participants had to have received maintenance treatment for at least three months. We excluded studies assessing enteral diet, diet manipulation, herbal medicine, and nutritional supplementation. DATA COLLECTION AND ANALYSIS Two review authors independently selected relevant studies, extracted data, and assessed the risk of bias. Any disagreements were resolved by discussion or by arbitration of a third review author when necessary. We conducted a network meta-analysis (NMA) using a Bayesian approach through Markov Chain Monte Carlo (MCMC) simulation. For the pairwise comparisons carried out in Review Manager 5, we calculated risk ratios (RR) with their corresponding 95% confidence intervals (95% CI). For the NMA, we presented hazard ratios (HR) with corresponding 95% credible intervals (95% CrI) and reported ranking probabilities for each intervention. For the NMA, we focused on three main outcomes: clinical relapse, endoscopic relapse, and withdrawals due to adverse events. Data were insufficient to assess time to relapse and histologic relapse. Adverse events and serious adverse events were not sufficiently or objectively reported to permit an NMA. We used CINeMA (Confidence in Network Meta-Analysis) methods to evaluate our confidence in the findings within networks, and GRADE for entire networks. MAIN RESULTS We included 35 RCTs (3249 participants) in the review. The average age of study participants ranged between 33.6 and 38.8 years. Risk of bias was high in 18 studies, low in four studies, and unclear in 13 studies. Of the 35 included RCTs, 26 studies (2581 participants; 9 interventions) were considered eligible for inclusion in the NMA. The interventions studied included 5-aminosalicylic acid (5-ASA), adalimumab, antibiotics, budesonide, infliximab, probiotics, purine analogues, sulfasalazine, and a combination of sulfasalazine and prednisolone. This resulted in 30 direct contrasts, which informed 102 mixed-treatment contrasts.The evidence for the clinical relapse network (21 studies; 2245 participants) and endoscopic relapse (12 studies; 1128 participants) were of low certainty while the evidence for withdrawal due to adverse events (15 studies; 1498 participants) was of very low certainty. This assessment was due to high risk of bias in most of the studies, inconsistency, and imprecision across networks. We mainly judged individual contrasts as of low or very low certainty, except 5-ASA versus placebo, the evidence for which was judged as of moderate certainty.We ranked the treatments based on effectiveness and the certainty of the evidence. For clinical relapse, the five most highly ranked treatments were adalimumab, infliximab, budesonide, 5-ASA, and purine analogues. We found some evidence that adalimumab (HR 0.11, 95% Crl 0.02 to 0.33; low-certainty evidence) and 5-ASA may reduce the probability of clinical relapse compared to placebo (HR 0.69, 95% Crl 0.53 to 0.87; moderate-certainty evidence). However, budesonide may not be effective in preventing clinical relapse (HR 0.66, 95% CrI 0.27 to 1.34; low-certainty evidence). We are less confident about the effectiveness of infliximab (HR 0.36, 95% CrI 0.02 to 1.74; very low-certainty evidence) and purine analogues (HR 0.75, 95% CrI 0.55 to 1.00; low-certainty evidence). It was unclear whether the other interventions reduced the probability of a clinical relapse, as the certainty of the evidence was very low.Due to high risk of bias and limited data across the network, we are uncertain about the effectiveness of interventions for preventing endoscopic relapse. Whilst there might be some evidence of prevention of endoscopic relapse with adalimumab (HR 0.10, 95% CrI 0.01 to 0.32; low-certainty evidence), no other intervention studied appeared to be effective.Due to high risk of bias and limited data across the network, we are uncertain about the effectiveness of interventions for preventing withdrawal due to adverse events. Withdrawal due to adverse events appeared to be least likely with sulfasalazine (HR 1.96, 95% Crl 0.00 to 8.90; very low-certainty evidence) and most likely with antibiotics (HR 53.92, 95% Crl 0.43 to 259.80; very low-certainty evidence). When considering the network as a whole, two adverse events leading to study withdrawal (i.e. pancreatitis and leukopenia) occurred in more than 1% of participants treated with an intervention. Pancreatitis occurred in 2.8% (11/399) of purine analogue participants compared to 0.17% (2/1210) of all other groups studied. Leukopenia occurred in 2.5% (10/399) of purine analogue participants compared to 0.08% (1/1210) of all other groups studied. AUTHORS' CONCLUSIONS Due to low-certainty evidence in the networks, we are unable to draw conclusions on which treatment is most effective for preventing clinical relapse and endoscopic relapse. Evidence on the safety of the interventions was inconclusive, however cases of pancreatitis and leukopenia from purine analogues were evident in the studies. Larger trials are needed to further understand the effect of the interventions on endoscopic relapse.
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Affiliation(s)
| | - Morris Gordon
- University of Central LancashireSchool of MedicineHarrington BuildingPrestonLancashireUK
| | - Andrew Clegg
- University of Central LancashireFaculty of Health and WellbeingBrook BuildingVictoria StreetPrestonLancashireUKPR1 2HE
| | - Suzanne C Freeman
- University of LeicesterDepartment of Health SciencesUniversity RoadLeicesterUKLE1 7RH
| | - Teuta Gjuladin‐Hellon
- University of Central LancashireSchool of MedicineHarrington BuildingPrestonLancashireUK
| | - John K MacDonald
- University of Western OntarioDepartment of MedicineLondonONCanada
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9
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Kato J, Yoshida T, Hiraoka S. Prediction of treatment outcome and relapse in inflammatory bowel disease. Expert Rev Clin Immunol 2019; 15:667-677. [PMID: 30873890 DOI: 10.1080/1744666x.2019.1593140] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Prediction of treatment outcome and clinical relapse in patients with inflammatory bowel disease (IBD), either ulcerative colitis (UC) or Crohn's disease (CD), is particularly important because therapeutics for IBD are not always effective and patients in remission could frequently relapse. Because undergoing endoscopy for the purpose is sometimes invasive and burdensome to patients, the performance of surrogate biomarkers has been investigated. Areas covered: We particularly featured the performance of patient symptoms, blood markers including C-reactive protein (CRP), fecal markers including fecal calprotectin (Fcal) and fecal immunochemical test (FIT) for prediction of endoscopic mucosal healing (MH) and prediction of relapse. Studies of other modalities and therapeutic drug monitoring (TDM) have also been explored. Expert opinion: Meticulous evaluation of patient symptoms could be predictive for MH in UC. CRP and Fcal may be accurate in prediction of MH of CD when MH is evaluated throughout the entire intestine including the small bowel. Repeated measurements of fecal markers including Fcal and FIT in patients with clinical remission would raise predictability of relapse. Prediction of treatment outcome by monitoring with blood markers including CRP, fecal markers including Fcal, and TDM has frequently been performed in recent clinical trials and shown to be effective.
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Affiliation(s)
- Jun Kato
- a Department of Gastroenterology , Mitsui Memorial Hospital , Tokyo , Japan
| | - Takeichi Yoshida
- b Second Department of Internal Medicine , Wakayama Medical University , Wakayama , Japan
| | - Sakiko Hiraoka
- c Department of Gastroenterology and Hepatology , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan
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10
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Wright EK, Kamm MA, De Cruz P, Hamilton AL, Selvaraj F, Princen F, Gorelik A, Liew D, Prideaux L, Lawrance IC, Andrews JM, Bampton PA, Jakobovits SL, Florin TH, Gibson PR, Debinski H, Macrae FA, Samuel D, Kronborg I, Radford-Smith G, Gearry RB, Selby W, Bell SJ, Brown SJ, Connell WR. Anti-TNF Therapeutic Drug Monitoring in Postoperative Crohn's Disease. J Crohns Colitis 2018; 12:653-661. [PMID: 29385469 DOI: 10.1093/ecco-jcc/jjy003] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2017] [Accepted: 01/13/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Anti-TNF prevents postoperative Crohn's disease recurrence in most patients but not all. This study aimed to define the relationship between adalimumab pharmacokinetics, maintenance of remission and recurrence. METHODS As part of a study of postoperative Crohn's disease management, some patients undergoing resection received prophylactic postoperative adalimumab. In these patients, serum and fecal adalimumab concentration and serum anti-adalimumab antibodies [AAAs] were measured at 6, 12 and 18 months postoperatively. Levels of Crohn's disease activity index [CDAI], C-reactive protein [CRP] and fecal calprotectin [FC] were assessed at 6 and 18 months postoperatively. Body mass index and smoking status were recorded. A colonoscopy was performed at 6 and/or 18 months. RESULTS Fifty-two patients [32 on monotherapy and 20 on combination therapy with thiopurine] were studied. Adalimumab concentration did not differ significantly between patients in endoscopic remission vs recurrence [Rutgeerts ≥ i2] [9.98µg/mL vs 8.43 µg/mL, p = 0.387]. Patients on adalimumab monotherapy had a significantly lower adalimumab concentration [7.89 µg/mL] than patients on combination therapy [11.725 µg/mL] [p = 0.001], and were significantly more likely to have measurable AAA [31% vs 17%, p = 0.001]. Adalimumab concentrations were lower in patients with detectable AAA compared with those without [3.59 µg/mL vs 12.0 µg/mL, p < 0.001]. Adalimumab was not detected in fecal samples. Adalimumab serum concentrations were lower in obese patients compared with in non-obese patients [p = 0.046]. CONCLUSION Adalimumab concentration in patients treated with adalimumab to prevent symptomatic endoscopic recurrence postoperatively is, for most patients, well within the therapeutic window, and is not significantly lower in patients who develop recurrence compared with in those who remain in remission. Mechanisms of anti-TNF failure to prevent postoperative recurrence remain to be determined in these patients.
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Affiliation(s)
- Emily K Wright
- Department of Gastroenterology, St Vincent's Hospital and University of Melbourne, Melbourne, Australia
| | - Michael A Kamm
- Department of Gastroenterology, St Vincent's Hospital and University of Melbourne, Melbourne, Australia
| | - Peter De Cruz
- Department of Gastroenterology, St Vincent's Hospital and University of Melbourne, Melbourne, Australia
| | - Amy L Hamilton
- Department of Gastroenterology, St Vincent's Hospital and University of Melbourne, Melbourne, Australia
| | - Fabiyola Selvaraj
- Department of Research and Development, Prometheus Laboratories, Inc., San Diego, California, USA
| | - Fred Princen
- Department of Research and Development, Prometheus Laboratories, Inc., San Diego, California, USA
| | - Alexandra Gorelik
- Melbourne EpiCentre, University of Melbourne and Melbourne Health, Melbourne, Australia
| | - Danny Liew
- Monash University, School of Public Health and Preventative Medicine, Melbourne, Australia
| | - Lani Prideaux
- Department of Gastroenterology, St Vincent's Hospital and University of Melbourne, Melbourne, Australia
| | - Ian C Lawrance
- Centre for Inflammatory Bowel Diseases, Fremantle Hospital and The University of Western Australia, Fremantle, Australia
| | - Jane M Andrews
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital and University of Adelaide, Adelaide, Australia
| | - Peter A Bampton
- Department of Gastroenterology and Hepatology, Flinders Medical Centre and Flinders University, Adelaide, Australia
| | | | - Timothy H Florin
- Department of Gastroenterology, Mater Health Services, University of Queensland Brisbane, Australia
| | - Peter R Gibson
- Department of Gastroenterology, Alfred Health and Monash University, Melbourne, Australia
| | - Henry Debinski
- Melbourne Gastrointestinal Investigation Unit, Cabrini Hospital, Melbourne, Australia
| | - Finlay A Macrae
- Department of Colorectal Medicine and Genetics, and Department of Medicine, Royal Melbourne Hospital and University of Melbourne, Melbourne, Australia
| | - Douglas Samuel
- Department of Gastroenterology, Bankstown Hospital, Sydney, Australia
| | - Ian Kronborg
- Department of Gastroenterology, Western Hospital, Melbourne, Australia
| | - Graham Radford-Smith
- Department of Gastroenterology, Royal Brisbane and Women's Hospital, Brisbane, Australia.,IBD Group Queensland Institute of Medical Research, University of Queensland, Brisbane, Australia
| | - Richard B Gearry
- Department of Medicine, University of Otago, Christchurch, New Zealand
| | - Warwick Selby
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, Australia
| | - Sally J Bell
- Department of Gastroenterology, St Vincent's Hospital and University of Melbourne, Melbourne, Australia
| | - Steven J Brown
- Department of Gastroenterology, St Vincent's Hospital and University of Melbourne, Melbourne, Australia
| | - William R Connell
- Department of Gastroenterology, St Vincent's Hospital and University of Melbourne, Melbourne, Australia
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11
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Bodini G, Giannini EG, Savarino V, Del Nero L, Lo Pumo S, Brunacci M, De Bortoli N, Jain A, Tolone S, Savarino E. Infliximab trough levels and persistent vs transient antibodies measured early after induction predict long-term clinical remission in patients with inflammatory bowel disease. Dig Liver Dis 2018; 50:452-456. [PMID: 29274766 DOI: 10.1016/j.dld.2017.11.008] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2017] [Revised: 11/16/2017] [Accepted: 11/16/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND The use of therapeutic drug monitoring has been proposed as a useful tool in the management of patients with loss of response to biological therapy in patients with inflammatory bowel disease. AIMS To evaluate whether early, post-induction anti-tumor necrosis factor trough levels and the presence of different types of anti-drug antibodies may impact long-term clinical remission in patients with inflammatory bowel disease. METHODS We prospectively assessed anti-tumor necrosis factor trough levels and both persistent and transient anti-drug antibodies. The Harvey-Bradshaw Index and the partial Mayo score were evaluated at each visit or in case of relapse. RESULTS At week 14, median infliximab trough levels were significantly lower in patients who experienced loss of response at week 48 as compared to patients in stable remission (1.3mcg/mL [range 0-10.2mcg/mL] vs. 10.1mcg/mL[range 0-42.8mcg/mL], P<0.0004). ROC curve identified an infliximab trough levels of 6.2mcg/mL as the cut-off value with the highest accuracy (c-index=0.864) for loss of response at week 48. At week 14 we observed a correlation between anti-drug antibodies concentration and infliximab trough levels (rs=-0.513, P=0.04). CONCLUSIONS The results highlight the usefulness of assessing early biological TL in order to predict patients' long-term outcome.
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Affiliation(s)
- Giorgia Bodini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy.
| | - Edoardo G Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Vincenzo Savarino
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Lorenzo Del Nero
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Sara Lo Pumo
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Matteo Brunacci
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Nicola De Bortoli
- Gastroenterology Unit, Department of Internal Medicine, University of Pisa, Pisa, Italy
| | - Anjali Jain
- Department of Research and Development, Prometheus Laboratories Inc., San Diego, CA, USA
| | - Salvatore Tolone
- Department of Surgery, Second University of Naples, Naples, Italy
| | - Edoardo Savarino
- Gastroenterolgy Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
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12
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Fay S, Ungar B, Paul S, Levartovsky A, Yavzori M, Fudim E, Picard O, Eliakim R, Ben-Horin S, Roblin X, Kopylov U. The Association Between Drug Levels and Endoscopic Recurrence in Postoperative Patients with Crohn's Disease Treated with Tumor Necrosis Factor Inhibitors. Inflamm Bowel Dis 2017; 23:1924-1929. [PMID: 28837524 DOI: 10.1097/mib.0000000000001220] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Endoscopic recurrence is associated with a risk of clinical recurrence in patients with Crohn's disease after ileocecal or small bowel resection. Drug levels and presence of antidrug antibodies are associated with important clinical and endoscopic outcomes in patients with Crohn's disease treated with tumor necrosis factor inhibitors, such association was not evaluated for endoscopic postsurgical recurrence. METHODS Consecutive patients with Crohn's disease treated with anti-tumor necrosis factors after surgery were identified in the databases of the participating centers. Anti-tumor necrosis factor levels and antidrug antibodies were correlated with Rutgeerts score on colonoscopy performed ≥6 months postoperatively. Significant endoscopic recurrence (SER) was defined as Rutgeerts score >2. RESULTS Seventy-three consecutive patients (32-infliximab, 41-adalimumab) were included in the study. The colonoscopies were performed after a median of 15 (7-43) months after surgery and 8 (6-15) months from treatment onset. SER was demonstrated in 26/73 (35.6%) of the patients. The need for dose optimization, as well as trough infliximab levels (2.4 μg/mL [0.45-4.1] versus 1.1 (0-0.6), P = 0.008) and presence of antidrug antibodies (1/18 [5.6%] versus 10/14 [71.4%], P = 0.0001) were significantly associated with a risk of SER. The optimal cutoff infliximab level for prediction of SER was 1.8 μg/mL. No association between adalimumab levels and antiadalimumab antibodies was demonstrated.
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Affiliation(s)
- Shmuel Fay
- *Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel, and Sackler Medical School, Tel Aviv University, Tel Aviv, Israel; and †Service de Gastrologie-Entérologie-Hépatologie, CHU de Saint-Etienne, Saint-Etienne, France
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13
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Gonczi L, Kurti Z, Rutka M, Vegh Z, Farkas K, Lovasz BD, Golovics PA, Gecse KB, Szalay B, Molnar T, Lakatos PL. Drug persistence and need for dose intensification to adalimumab therapy; the importance of therapeutic drug monitoring in inflammatory bowel diseases. BMC Gastroenterol 2017; 17:97. [PMID: 28789636 PMCID: PMC5549364 DOI: 10.1186/s12876-017-0654-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2017] [Accepted: 07/31/2017] [Indexed: 02/06/2023] Open
Abstract
Background Therapeutic drug monitoring (TDM) aid therapeutic decision making in patients with inflammatory bowel disease (IBD) who lose response to anti-TNF therapy. Our aim was to evaluate the frequency and predictive factors of loss of response (LOR) to adalimumab using TDM in IBD patients. Methods One hundred twelve IBD patients (with 214 TDM measurements, CD/UC 84/28, male/female 50/62, mean age CD/UC: 36/35 years) were enrolled in this consecutive cohort from two referral centres in Hungary. Demographic data were comprehensively collected and harmonized monitoring strategy was applied. Previous and current therapy, laboratory data and clinical activity were recorded at the time of TDM. Patients were evaluated either at the time of suspected LOR or during follow-up. TDM measurements were determined by commercial ELISA (LISA TRACKER, Theradiag, France). Results Among 112 IBD patients, LOR/drug persistence was 25.9%/74.1%. The cumulative ADA positivity (>10 ng/mL) and low TL (<5.0 μg/mL) was 12.1% and 17.8% after 1 year and 17.3% and 29.5% after 2 years of adalimumab therapy. Dose intensification was needed in 29.5% of the patients. Female gender and ADA positivity were associated with LOR (female gender: p < 0.001, OR:7.8 CI 95%: 2.5–24.3, ADA positivity: p = 0.007 OR:3.6 CI 95%: 1.4–9.5). Conclusions ADA development, low TL and need for dose intensification were frequent during adalimumab therapy and support the selective use of TDM in IBD patients treated with adalimumab. ADA positivity and gender were predictors of LOR. Electronic supplementary material The online version of this article (doi:10.1186/s12876-017-0654-1) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Lorant Gonczi
- First Department of Medicine, Semmelweis University, Koranyi S 2A, Budapest, H-1083, Hungary
| | - Zsuzsanna Kurti
- First Department of Medicine, Semmelweis University, Koranyi S 2A, Budapest, H-1083, Hungary
| | - Mariann Rutka
- First Department of Medicine, University of Szeged, Szeged, Hungary
| | - Zsuzsanna Vegh
- First Department of Medicine, Semmelweis University, Koranyi S 2A, Budapest, H-1083, Hungary
| | - Klaudia Farkas
- First Department of Medicine, University of Szeged, Szeged, Hungary
| | - Barbara D Lovasz
- First Department of Medicine, Semmelweis University, Koranyi S 2A, Budapest, H-1083, Hungary.,Institute of Applied Health Sciences, Semmelweis University, Budapest, Hungary
| | - Petra A Golovics
- First Department of Medicine, Semmelweis University, Koranyi S 2A, Budapest, H-1083, Hungary
| | - Krisztina B Gecse
- First Department of Medicine, Semmelweis University, Koranyi S 2A, Budapest, H-1083, Hungary
| | - Balazs Szalay
- Department of Laboratory Medicine, Semmelweis University, Budapest, Hungary
| | - Tamas Molnar
- First Department of Medicine, University of Szeged, Szeged, Hungary
| | - Peter L Lakatos
- First Department of Medicine, Semmelweis University, Koranyi S 2A, Budapest, H-1083, Hungary. .,Division of Gastroenterology, McGill University, MUHC, Montreal General Hospital, 1650 Ave. Cedar, D16.173. 1, Montreal, QC, H3G 1A4, Canada.
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14
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Bodini G, Giannini EG, De Maria C, Dulbecco P, Furnari M, Marabotto E, Savarino V, Savarino E. Anti-TNF therapy is able to stabilize bowel damage progression in patients with Crohn's disease. A study performed using the Lémann Index. Dig Liver Dis 2017; 49:175-180. [PMID: 27864028 DOI: 10.1016/j.dld.2016.10.014] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Revised: 10/10/2016] [Accepted: 10/23/2016] [Indexed: 12/11/2022]
Abstract
AIMS The Lémann Index (LI) was developed to assess the cumulative structural damage of the intestinal tract in patients with Crohn's Disease (CD) independently of clinical and biochemical activity. Recently, the goal of CD focused on obtaining mucosal healing and deep remission rather than simple symptom control. These new therapeutic aims emphasize the need to prevent progression of bowel damage. In this study we aimed to evaluate the influence of different treatments on structural damage progression, assessed by means of LI in a series of CD patients consistently treated with various drugs. METHODS The LI was calculated at inclusion and at the end of follow-up in 104 CD patients subdivided according to treatments received: biological drugs (n=40, 38.4%), azathioprine (n=19, 18.3%), and mesalazine (n=45, 43.3%). RESULTS The median follow-up was 29 months, with no difference among groups. During follow-up, the median LI was stable in the biological group [from 6.3 (range, 0.6-37.3) to 6.4 (range, 0.6-37.6), P=0.543], whereas it significantly increased from 4.1 (range, 0.6-30) to 8.3 (range, 0.6-31.8) in the azathioprine group (P=0.0006), and from 2.4 (range, 0.6-25.8) to 4.1 (range, 0.6-28.8) in the mesalazine group (P<0.0001). Also during follow-up the LI increased significantly (P=0.004) in the azathioprine (68.4%) and mesalazine (60.0%) groups as compared with the biological therapy group (30.0%). CONCLUSIONS In CD patients the LI tends to increase over time, although the use of biological drugs rather than azathioprine or mesalazine seems to be able to reduce the progressive bowel damage.
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Affiliation(s)
- Giorgia Bodini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy.
| | - Edoardo G Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Costanza De Maria
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Pietro Dulbecco
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Manuele Furnari
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Elisa Marabotto
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Vincenzo Savarino
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Edoardo Savarino
- Gastroenterolgy Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
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15
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Campbell JP, Vaughn BP. Optimal delivery of follow-up care after surgery for Crohn's disease: current perspectives. Clin Exp Gastroenterol 2016; 9:237-48. [PMID: 27540307 PMCID: PMC4982489 DOI: 10.2147/ceg.s96078] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Despite improvements in medical therapies for Crohn’s disease (CD), up to 70% of patients require surgery within 10 years of diagnosis. Surgery is not curative, and almost all patients will experience endoscopic recurrence, and many will go on to clinical recurrence. Identifying patients at high-risk of endoscopic recurrence and standardizing postoperative assessments are essential in preventing clinical recurrence of CD. In this review, we discuss the assessment, monitoring, and treatment of postoperative CD patients. We address the various individual risk factors as well as composite risk factors. Medications used for primary CD treatment can be used in the postoperative setting to prevent endoscopic or clinical recurrence with varying efficacy, although the cost-effectiveness of these approaches are not fully understood. Future directions for postoperative CD management include evaluation of newer biologic agents such as anti-integrin therapy and fecal microbiota transplant for prevention of recurrence. Development of a standard preoperative risk assessment tool to clearly stratify those at high-risk of recurrence is necessary to guide empiric therapy. Lastly, the incorporation of noninvasive testing into disease monitoring will likely lead to early detection of endoscopic recurrence that will allow for tailored treatment to prevent clinical recurrence.
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Affiliation(s)
- James P Campbell
- Department of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, MN, USA
| | - Byron P Vaughn
- Department of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, MN, USA
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16
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Pelletier AL, Nicaise-Roland P. Adalimumab and pharmacokinetics: Impact on the clinical prescription for inflammatory bowel disease. World J Pharmacol 2016; 5:44-50. [DOI: 10.5497/wjp.v5.i1.44] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2015] [Revised: 11/19/2015] [Accepted: 12/14/2015] [Indexed: 02/06/2023] Open
Abstract
Anti-tumor necrosis factor (TNF) drugs are widely prescribed for inflammatory disease. A loss of response to adalimumab is frequent and the pharmacokinetics of anti-TNF therapy have important implications for patient management. Individual factors such as albumin, body weight, and disease severity based on the C-reactive protein level influence drug metabolism. Adalimumab trough levels are associated with clinical remission. On the other hand, the detection of antibodies is associated with clinical relapse. Immunosuppressive therapy could reduce antibody formation although the clinical impact is not proven. New algorithms are available to provide personalized treatment and adapt the dosage. More data are needed on dose de-escalation.
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