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. 2024 Sep 9;73(10):1763-1773.
doi: 10.1136/gutjnl-2024-332489.

Acute severe ulcerative colitis trials: the past, the present and the future

Sailish Honap  1   2 , Vipul Jairath  3   4 , Bruce E Sands  5 , Parambir S Dulai  6 , Silvio Danese  7 , Laurent Peyrin-Biroulet  8   9
Affiliations

Acute severe ulcerative colitis trials: the past, the present and the future

Sailish Honap et al. Gut. .

Abstract

Acute severe ulcerative colitis (ASUC), characterised by bloody diarrhoea and systemic inflammation, is associated with a significant risk of colectomy and a small risk of mortality. The landmark trial of cortisone in 1955 was pivotal for two reasons: first, for establishing the efficacy of a drug that remains a first-line therapy today and, second, for producing the first set of disease severity criteria and clinical trial endpoints that shaped the subsequent ASUC trial landscape. Trials in the 1990s and at the turn of the millennium established the efficacy of infliximab and ciclosporin, but since then, there has been little progress in drug development for this high-risk population. This systematic review evaluates all interventional randomised controlled trials (RCTs) conducted in patients hospitalised with severe UC. It provides an overview of the efficacy of treatments from past to present and assesses the evolution of trial characteristics with respect to study populations, eligibility criteria and study designs over time. This review details ongoing RCTs in this field and provides a perspective on the challenges for future clinical trial programmes and how these can be overcome to help deliver novel ASUC therapies.

Keywords: CHRONIC ULCERATIVE COLITIS; CLINICAL TRIALS; DRUG DEVELOPMENT; INFLAMMATORY BOWEL DISEASE; ULCERATIVE COLITIS.

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Conflict of interest statement

Competing interests: SH served as a speaker, a consultant and/or an advisory board member for Pfizer, Janssen, AbbVie, Lilly and Takeda, and in addition, she has received travel grants from Ferring, Pharmacosmos, Falk Pharma. VJ reports personal fees from AbbVie, Alimentiv (formerly Robarts Clinical Trials), Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, AstraZeneca, Avoro Capital, BMS, Celltrion, Endpoint Health, Enthera, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, Gilde Healthcare, GSK, Genentech, Gilead, Innomar, JAMP, Janssen, Lilly, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus, Reistone Biopharma, Roche, Roivant, Sandoz, SCOPE, Second Genome, Sorriso Pharmaceuticals, Takeda, Teva, Topivert, Ventyx and Vividion outside the submitted work and fees from advisory board membership of AbbVie, Alimentiv (formerly Robarts Clinical Trials), Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, AstraZeneca, BMS, Celltrion, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, Gilde Healthcare, GSK, Genentech, Gilead, Innomar, JAMP, Janssen, Lilly, Merck, Metacran, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus, Reistone Biopharma, Roche, Sandoz, SCOPE, Second Genome, Sorriso Pharmaceuticals, Takeda, Teva, Topivert, Ventyx and Vividion. BES reports consulting fees from Abbvie, Alimentiv, Amgen, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, Boehringer Ingelheim, Boston Pharmaceuticals, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Evommune, Fresenius Kabi, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, IndexPharmaceuticals, Innovation Pharmaceuticals, Inotrem, Kaleido, Kallyope, Merck, Morphic Therapeutics, MRM Health, Progenity, Prometheus, Protagonist Therapeutics, Q32 Bio, Sun Pharma, Surrozen, Target RWE, Teva, TLL Pharmaceutical, Ventyx Biosciences; consulting and speaking fees from Abivax; consulting and speaking fees and other support from Lilly; research grants, consulting and speaking fees and other support from Bristol Myers Squibb, Janssen, Pfizer, Takeda; research grants and consulting fees from Theravance Biopharma; and stock options from Ventyx Biopharma. PSD received consulting fees from Abbvie, Abivax, Adiso, Bristol Myers Squibb, GSK, Janssen, Lilly, Pfizer and Takeda and grant support from Bristol-Myers Squibb, Janssen, Pfizer and Takeda and licensing royalties from PreciDiag. SD has served as a speaker, consultant and advisory board member for Schering-Plough, AbbVie, Actelion, Alfa Wasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grunenthal, Johnson & Johnson, Millennium/Takeda, MSD, Nikkiso Europe GmbH, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, UCB and Vifor. LPB reports consulting fees from Abbvie, Abivax, Adacyte, Alimentiv, Amgen, Applied Molecular Transport, Arena, Banook, Biogen, BMS, Celltrion, Connect Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, IAC Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Nordic Pharma, Novartis, Oncodesign Precision Medicine, ONO Pharma, OSE Immunotherapeuthics, Pandion Therapeuthics, Par' Immune, Pfizer, Prometheus, Protagonist, Roche, Samsung, Sandoz, Sanofi, Satisfay, Takeda, Telavant, Theravance, Thermo Fischer, Tigenix, Tillots, Viatris, Vectivbio, Ventyx, Ysopia, Grant support from Celltrion, Fresenius Kabi, Medac, MSD, Takeda. Lecture fees from Abbvie, Amgen, Arena, Biogen, Celltrion, Ferring, Galapagos, Genentech, Gilead, Janssen, Lilly, Medac, MSD, Nordic Pharma, Pfizer, Sandoz, Takeda, Tillots, Viatris. Travel support fees from Abbvie, Amgen, Celltrion, Connect Biopharm, Ferring, Galapagos, Genentech, Gilead, Gossamer Bio, Janssen, Lilly, Medac, Morphic, MSD, Pfizer, Sandoz, Takeda, Thermo Fischer, Tillots.

Figures

Figure 1
Figure 1
Evolution of randomised controlled trials for hospitalised ulcerative colitis patients from 1955-2023 categorised by time and intervention
See this image and copyright information in PMC

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