Original ResearchFull Report: Clinical—Alimentary TractSTRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD
Section snippets
Methods
This project has been developed as part of the IOIBD endpoints cluster initiative and followed several stages to reach consensus among international IBD experts after careful review of existing evidence. A flow diagram of the various consensus procedures including the Delphi-like process and the systematic literature review is depicted in Figure 1. A steering committee of 10 IOIBD members formulated the search questions and scope. A systematic review of the literature was performed in July 2019
Results
In total, 11,278 abstracts were screened in duplicate (6223 in CD and 5055 in UC), 1005 were reviewed as full text (413 in CD and 592 in UC) and 435 manuscripts (297 in CD and 138 in UC) were eventually included in the summary of evidence (Appendices under Supplementary Material). The following reasons for exclusion included among others: inappropriate follow-up period, reviews, irrelevant targets, small case series, and language other than English.
The Delphi group suggested and ranked the
Conclusion
STRIDE-II confirms that the most important long-term achievable treatment targets for patients with IBD are clinical remission, EH, restoration of QoL, and absence of disability. Symptomatic relief has been determined as an immediate goal, acknowledging that this is rated highest by patients in studies. With the accumulating clinical evidence, serum and fecal biomarkers are endorsed as intermediate medium-term feasible treatment goals, meaning that at times treatment could be revisited solely
Acknowledgments
The authors thank the informatician Ms Iris Arad for performing the systematic electronic search of the evidence, Ms Tamar Altaraz for administrative assistance, and all IOIBD members for providing their input via the multiple surveys and Delphi-like process.
CRediT Authorship Contributions
Dan Turner, MD, PhD (Conceptualization: Lead; Data curation: Lead; Formal analysis: Lead; Methodology: Lead; Project administration: Lead; Supervision: Lead; Writing – original draft: Lead; Writing – review & editing: Lead). Amanda
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Conflict of Interest These authors disclose the following: Axel Dignass has received research support or acted as a principal investigator for AbbVie, Dr. Falk Pharma, Celgene, Gilead, Janssen and Takeda; has acted as a consultant for AbbVie, Amgen, BMS, Boehringer Ingelheim, Celgene, Dr Falk Pharma, Ferring, Fresenius Kabi, Celltrion, Janssen, MSD, Pfizer, Roche, Takeda, Tillotts, and Vifor; and has participated in speaker bureaus for AbbVie, Falk Foundation, Ferring, Janssen, Med Update, MSD, Pfizer, Roche, Takeda, Tillotts, and Vifor. David T. Rubin has received research funding from Takeda, and has served as a consultant to AbbVie, Abgenomics, Allergan, Inc., Arena Pharmaceuticals, Biomica, Bristol-Myers Squibb, Dizal Pharmaceuticals, Ferring Pharmaceuticals, Inc., Genentech/Roche, Janssen Pharmaceuticals, Lilly, Mahana Therapeutics, Medtronic, Merck & Co., Inc, Napo Pharmaceuticals, Pfizer, Prometheus Laboratories, Shire, Takeda, and Target PharmaSolutions, Inc and is a co-founder of Cornerstones Health, Inc. Dan Turner received consultation fee, research grant, royalties, or honorarium from Janssen, Pfizer, Hospital for Sick Children, Ferring, Abbvie, Takeda, Atlantic Health, Shire, Celgene, Lilly, Roche, ThermoFisher, and BMS. Dominik Bettenworth is on the advisory board or consultant for Amgen, AbbVie, Dr. Falk Foundation, Ferring, MSD, Pfizer, Pharmacosmos, Roche, Takeda, Tillotts Pharma, and Vifor. Silvio Danese has served as a speaker, consultant, and advisory board member for Schering-Plough, AbbVie, Actelion, Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grünenthal, Johnson and Johnson, Millenium Takeda, MSD, Nikkiso Europe GmbH, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, UCB Pharma and Vifor. Laurent Peyrin-Biroulet has received personal fees from AbbVie, Janssen, Genentech, Ferring, Tillots, Pharmacosmos, Celltrion, Takeda, Boerhinger Ingelheim, Pfizer, Index Pharmaceuticals, Sandoz, Celgene, Biogen, Samsung Bioepis, Alma, Sterna, Nestle, Enterome, Allergan, MSD, Roche, Arena, Gilead, Hikma, Amgen, BMS, Vifor, Norgine, Mylan, Lilly, Fresenius Kabi, Oppilan Pharma, Sublimity Therapeutics, Applied Molecular Transport, OSE Immunotherapeutics, Enthera, Theravance; grants from AbbVie, MSD, and Takeda; and stock options from CTMA. Iris Dotan has served as a speaker, consultant, and advisory board member for Takeda, Janssen, AbbVie, Pfizer, Ferring, Roche/Genentech, Celgene/BMS, Falk Pharma, Rafa Laboratories, Neopharm, Nestle, Arena, Gilead, MSD, DSM, Celltrion, Sublimity, Sandoz, Abbott, and Athos therapeutics. Maria T. Abreu has served as a scientific advisory board member for Boehringer Ingelheim Pharmaceuticals, Gilead, AbbVie, Seres Therapeutics, Shire, and Landos Biopharma; served as a trainer or lecturer for Imedex, Focus Medical Communications, and Cornerstones Health, Inc.; has served as a consultant for Ferring Pharmaceuticals, Allergan, Amgen, Celltrion Healthcare CO, Millennium Pharmaceuticals, Theravance Biopharma Inc., and UCB Biopharma SRL; and has funded projects by Prometheus Laboratories and Pfizer. Walter Reinisch has served as a speaker for Abbott Laboratories, AbbVie, Aesca, Aptalis, Astellas, Centocor, Celltrion, Danone Austria, Elan, Falk Pharma GmbH, Ferring, Immundiagnostik, Mitsubishi Tanabe Pharma Corporation, MSD, Otsuka, PDL, Pharmacosmos, PLS Education, Schering-Plough, Shire, Takeda, Therakos, Vifor, and Yakult; served as a consultant for Abbott Laboratories, AbbVie, Aesca, Algernon, Amgen, AM Pharma, AMT, AOP Orphan, Arena Pharmaceuticals, Astellas, Astra Zeneca, Avaxia, Roland Berger GmBH, Bioclinica, Biogen IDEC, Boehringer Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Covance, Danone Austria, DSM, Elan, Eli Lilly, Ernest & Young, Falk Pharma GmbH, Ferring, Galapagos, Genentech, Gilead, Grünenthal, ICON, Index Pharma, Inova, Intrinsic Imaging, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, LivaNova, Mallinckrodt, Medahead, MedImmune, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Nash Pharmaceuticals, Nestle, Nippon Kayaku, Novartis, Ocera, OMass, Otsuka, Parexel, PDL, Periconsulting, Pharmacosmos, Philip Morris Institute, Pfizer, Procter & Gamble, Prometheus, Protagonist, Provention, Robarts Clinical Trial, Sandoz, Schering-Plough, Second Genome, Seres Therapeutics, Setpointmedical, Sigmoid, Sublimity, Takeda, Therakos, Theravance, Tigenix, UCB, Vifor, Zealand, Zyngenia, and 4SC; and served as an advisory board member for Abbott Laboratories, AbbVie, Aesca, Amgen, AM Pharma, Astellas, Astra Zeneca, Avaxia, Biogen IDEC, Boehringer Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Danone Austria, DSM, Elan, Ferring, Galapagos, Genentech, Grünenthal, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, MedImmune, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Nestle, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Sandoz, Schering-Plough, Second Genome, Setpointmedical, Takeda, Therakos, Tigenix, UCB, Zealand, Zyngenia, and 4SC. Jürgen Schölmerich declares lecture honoraria from AbbVie and Dr.Falk during the past 5 years. William Sandborn reports research grants from Atlantic Healthcare Limited, Amgen, Genentech, Gilead Sciences, AbbVie, Janssen, Takeda, Lilly, Celgene/Receptos,Pfizer, Prometheus Laboratories (now Prometheus Biosciences); consulting fees from AbbVie, Allergan, Amgen, Arena Pharmaceuticals, Avexegen Therapeutics, BeiGene, Boehringer Ingelheim, Celgene, Celltrion, Conatus, Cosmo, Escalier Biosciences, Ferring, Forbion, Genentech, Gilead Sciences, Gossamer Bio, Incyte, Janssen, Kyowa Kirin Pharmaceutical Research, Landos Biopharma, Lilly, Oppilan Pharma, Otsuka, Pfizer, Progenity, Prometheus Biosciences (merger of Precision IBD and Prometheus Laboratories), Reistone, Ritter Pharmaceuticals, Robarts Clinical Trials (owned by Health Academic Research Trust, HART), Series Therapeutics, Shire, Sienna Biopharmaceuticals, Sigmoid Biotechnologies, Sterna Biologicals, Sublimity Therapeutics, Takeda, Theravance Biopharma, Tigenix, Tillotts Pharma, UCB Pharma, Ventyx Biosciences, Vimalan Biosciences, Vivelix Pharmaceuticals; and stock or stock options from BeiGene, Escalier Biosciences, Gossamer Bio, Oppilan Pharma, Prometheus Biosciences (merger of Precision IBD and Prometheus Laboratories), Progenity, Ritter Pharmaceuticals, Ventyx Biosciences, Vimalan Biosciences. Spouse: Iveric Bio - consultant, stock options; Progenity - consultant, stock; Oppilan Pharma - consultant, stock options; Escalier Biosciences – prior employee, stock options; Prometheus Biosciences (merger of Precision IBD and Prometheus Laboratories) - employee, stock options; Ventyx Biosciences – stock options; Vimalan Biosciences – stock options. Willem Bemelman served as speaker for Johnson & Johnson, Braun and Takeda, and obtained research grants from Braun, VIFOR, and Medtronic. Bruce E. Sands discloses consulting fees from 4D Pharma, Abbvie, Allergan, Amgen, Arena Pharmaceuticals, AstraZeneca, BoehringerIngelheim, Boston Pharmaceuticals, Capella Biosciences, Celgene, Celltrion Healthcare, EnGene, Ferring, Genentech, Gilead, Hoffmann-La Roche, Immunic, Ironwood Pharmaceuticals, Janssen, Lilly, Lyndra, MedImmune, Morphic Therapeutic, Oppilan Pharma, OSE Immunotherapeutics, Otsuka, Palatin Technologies, Pfizer, Progenity, Prometheus Laboratories, Redhill Biopharma, Rheos Medicines, Seres Therapeutics, Shire, Synergy Pharmaceuticals, Takeda, Target PharmaSolutions, Theravance Biopharma R&D, TiGenix, and Vivelix Pharmaceuticals; honoraria for speaking in CME programs from Takeda, Janssen, Lilly, Gilead, Pfizer, Genetech; and research funding from Celgene, Pfizer, Takeda, Theravance Biopharma R&D, and Janssen. Anne Griffiths has served as a speaker or consultant or advisory board member for AbbVie, Amgen, Bristol Meyers Squibb, Celgene, Janssen, Lilly, Merck, Nestle, Pfizer, and Roche, and has received a research grant from AbbVie. Jean-Frederic Colombel reports receiving research grants from AbbVie, Janssen Pharmaceuticals and Takeda; receiving payment for lectures from AbbVie, Amgen, Allergan, Inc. Ferring Pharmaceuticals, Shire, and Takeda; receiving consulting fees from AbbVie, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene Corporation, Celltrion, Eli Lilly, Enterome, Ferring Pharmaceuticals, Geneva, Genentech, Janssen Pharmaceuticals, Landos, LimmaTech Biologics AG, Ipsen, Imedex, lmtbio, Medimmune, Merck, Novartis, O Mass, Ostuka, Pfizer, SERENE CD, Shire, Takeda, Tigenix, Viela bio; and holds stock options in Intestinal Biotech Development and Genfit. The remaining authors disclose no conflicts.
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Authors share co-first authorship.