Original ResearchFull Report: Clinical—Alimentary TractIdentification of Endpoints for Development of Antifibrosis Drugs for Treatment of Crohn’s Disease
Section snippets
Systematic Review of the Literature
We systematically searched the PubMed and Embase databases from their inception to June 2017. Search algorithms included Crohn’s disease combined with fibrosis or stricture, without any language restriction. We also searched ClinicalTrials.gov and bibliographies of relevant review articles. Randomized controlled trials, clinical controlled trials, and cohort, case-control, and cross-sectional studies were considered eligible if they included adult patients (≥18 years) with
Search results and description of included studies
Figure 1 (flow diagram) summarizes the search and selection process. A total of 61 eligible studies were included24, 25, 28, 31, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111 (Supplementary Table 1). The studies were of relatively small size (mean number of participants, 75; range, 9 to 438), with the
Discussion
Intestinal fibrosis remains one of the largest clinical challenges in therapeutic management of CD. More than one-half of the patients with CD develop clinically apparent fibrostenosis throughout their disease course,16 leading to frequent hospitalizations and surgical interventions.47 However, current therapies for CD (ie, steroids, immunosuppressants, and biologics) may not be effective for this indication, and specific drug therapies aiming at intestinal fibrosis are not available.19, 20, 21
Acknowledgments
We thank all the IOIBD experts who participated in the Delphi survey.
Author contributions: Silvio Danese and Laurent Peyrin-Biroulet were involved with conception and design of the study, acquisition and analysis of data, interpretation of data, critical revision of the manuscript for important intellectual content, and approval of the final version of the manuscript. Stefanos Bonovas, Anthony Lopez, and Gionata Fiorino were involved with conception and design of the study, acquisition and
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Challenges in the Pathophysiology, Diagnosis, and Management of Intestinal Fibrosis in Inflammatory Bowel Disease
2022, GastroenterologyCitation Excerpt :Nevertheless, evaluation of symptoms by rigorously developed PROs is also necessary to show the value of new treatments to patients’ well-being and for regulatory approval. Expert members of the International Organization for Inflammatory Bowel Disease recently proposed 13 end points for use in clinical trials that assess the efficacy and safety of antifibrotic agents in CD.8 Currently, the international STAR (Stenosis Therapy and Anti-Fibrotic Research) consortium is developing a PRO instrument for stricturing CD according to US Food and Drug Administration–recommended methodology and internationally developed best practices.
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Histopathology Scoring Systems of Stenosis Associated With Small Bowel Crohn's Disease: A Systematic Review
2020, GastroenterologyCitation Excerpt :Development of a fully validated histologic index is essential for validation of novel cross-sectional imaging techniques that may ultimately serve as outcome measures in clinical trials. The importance of developing endpoints for stenosing CD has been recognized by 2 international working groups.29,66 Proposed endpoints,29 including a patient-reported outcome tool, an MRI index, and a histopathology score, are being developed under the umbrella of the STAR consortium with involvement of interdisciplinary global expert panels, industry, and regulators.
Intestinal and hepatic fibrosis: how are they similar?
2019, The Lancet Gastroenterology and HepatologyNoninvasive Multimodal Methods to Differentiate Inflamed vs Fibrotic Strictures in Patients With Crohn's Disease
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Conflicts of interest Silvio Danese has served as a speaker, a consultant, and an advisory board member for AbbVie, Allergan, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Hospira, Johnson & Johnson, Merck, MSD, Takeda, Mundipharma, Pfizer, Sandoz, TiGenix, UCB Pharma, and Vifor. Stefanos Bonovas is supported by FIRMAD. Anthony Lopez has received research funding from Roche, has served as consultant for Amgen, and has received lecture fees from Vifor Pharma. Gionata Fiorino has served as a consultant and Advisory Board Member for MSD, AbbVie, Takeda, Janssen, Mundipharma, Sandoz, and Pfizer. William J. Sandborn reports grants, personal fees, and nonfinancial support from AbbVie; grants and personal fees from Prometheus Laboratories, Boehringer Ingelheim, Takeda, Atlantic Pharmaceuticals, Janssen, Bristol-Myers Squibb, Genentech, and Nutrition Science Partners; and personal fees from Kyowa Hakko Kirin, Millennium Pharmaceuticals, Celgene Cellular Therapeutics, Santarus, Salix Pharmaceuticals, Catabasis Pharmaceuticals, Vertex Pharmaceuticals, Warner Chilcott, Gilead Sciences, Cosmo Pharmaceuticals, Ferring Pharmaceuticals, Sigmoid Biotechnologies, Tillotts Pharma, Am Pharma BV, Dr August Wolff, Avaxia Biologics, Zyngenia, Ironwood Pharmaceuticals, Index Pharmaceuticals, Nestle, Lexicon Pharmaceuticals, UCB Pharma, Orexigen, Luitpold Pharmaceuticals, Baxter Healthcare, Ferring Research Institute, Amgen, Novo Nordisk, Mesoblast Inc., Shire, Ardelyx Inc., Actavis, Seattle Genetics, MedImmune (AstraZeneca), Actogenix NV, Lipid Therapeutics Gmbh, Eisai, Qu Biologics, Toray Industries Inc., Teva Pharmaceuticals, Eli Lilly, Chiasma, TiGenix, Adherion Therapeutics, Immune Pharmaceuticals, Celgene, Arena Pharmaceuticals, Ambrx Inc., Akros Pharma, Vascular Biogenics, Theradiag, Forward Pharma, Regeneron, Galapagos, Seres Health, Ritter Pharmaceuticals, Theravance, Palatin, Biogen, and Western University (owner of Robarts Clinical Trials). David T. Rubin has received consulting fees or research support from AbbVie, Abgenomics, Allergan, Amgen, Celgene, Forward Pharma, Genentech/Roche, Janssen, Merck, Miraca Life Sciences, Mitsubishi, Napo Pharmaceuticals, Pfizer, Prometheus Laboratories, Salix Pharmaceuticals, Shire, Takeda, Target PharmaSolutions, and UCB Pharma. Michael A. Kamm has received research funding support from AbbVie and Ferring, and has served as a consultant in the last 2 years to AbbVie, Janssen, MSD, Takeda, Pfizer, Celgene, and Ferring. Jean-Frederic Colombel has served as consultant, advisory board member, or speaker for AbbVie, Amgen, Boehringer Ingelheim, Celgene Corporation, Celltrion, Enterome, Ferring, Genentech, Janssen and Janssen, Lilly, Medimmune, Merck, Pfizer, PPM Services, Protagonist, Second Genome, Seres, Shire, Takeda, Theradiag, Theravance Biopharma, and TiGenix. Bruce E. Sands has served as a consultant for AbbVie, Akros Pharma, Allergan, Bristol-Myers Squibb, Lyndra, Lycera, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene, EnGene, Gilead, Janssen, Lilly, MedImmune, Oppilan Pharma, Pfizer, Shire, Takeda, Target Pharmasolutions, Theravance Biopharma R&D, TiGenix, Immune Pharmaceuticals, Receptos, TopiVert Pharma, UCB, Vivelix Pharmaceuticals, Synergy Pharmaceuticals, and Salix Pharmaceuticals. Severine Vermeire has received grant support from AbbVie, MSD, Pfizer, and Takeda; received speaker fees from AbbVie, MSD, Takeda, Ferring, Dr. Falk Pharma, Hospira, Pfizer, and Tillots; and served as a consultant for AbbVie, MSD, Takeda, Ferring, Genentech/Roche, Shire, Pfizer, Galapagos, Mundipharma, Hospira, Celgene, Second Genome, and Janssen. Julian Panes has served as a speaker, a consultant, or an advisory board member for AbbVie, Biogen, Boehringer Ingelheim, Celgene, Ferring, Johnson & Johnson, MSD, Nestle, Oppilan, Pfizer, Sandoz, Takeda, Theravance, and TiGenix. Gerhard Rogler has served as a speaker, a consultant, or an advisory board member for AbbVie, Amgen, Augurix, Boehringer, Bristol-Myers Squibb, Calypso, Celgene, Falk, Ferring, Fisher, Genentech, Gilead, Index Pharmaceuticals, Janssen, MSD, Novartis, Pfizer, Phadia, Roche, UCB, Takeda, Tillots, UCB, Vifor, Vital Solutions, and Zeller. Geert D’Haens has served as advisor for AbbVie, Ablynx, Amakem, Amgen, AM Pharma, Avaxia, Biogen, Bristol Meiers Squibb, Boehringer Ingelheim, Celgene/Receptos, Celltrion, Cosmo, Covidien/Medtronics, Ferring, Dr. Falk Pharma, Eli Lilly, Engene, Galapagos, Genentech/Roche, Gilead, Glaxo Smith Kline, Immunic, Johnson & Johnson, Lycera, Medimetrics, Millenium/Takeda, Mitsubishi Pharma, Merck Sharp Dome, Mundipharma, Nextbiotics, Novonordisk, Otsuka, Pfizer/Hospira, Prometheus Laboratories/Nestle, Protagonist, Robarts Clinical Trials, Salix, Samsung Bioepis, Sandoz, Setpoint, Shire, Teva, TiGenix, Tillotts, Topivert, Versant, and Vifor; and received speaker fees from AbbVie, Biogen, Ferring, Johnson and Johnson, Merck Sharp Dome, Mundipharma, Norgine, Pfizer, Samsung Bioepis, Shire, Millenium/Takeda, Tillotts, and Vifor. Laurent Peyrin-Biroulet has received consulting fees from AbbVie, Amgen, Biogaran, Biogen, Boerhinger-Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Ferring, Forward Pharma, Genentech, H.A.C. Pharma, Hospira, Index Pharmaceuticals, Janssen, Lycera, Merck, Lilly, Mitsubishi, Norgine, Pfizer, Pharmacosmos, Pilège, Samsung Bioepis, Sandoz, Takeda, Therakos, Tillots, UCB Pharma, and Vifor; and lecture fees from AbbVie, Ferring, H.A.C. Pharma, Janssen, Merck, Mitsubishi, Norgine, Takeda, Therakos, Tillots, and Vifor.
Author names in bold designate shared co-first authorship.