@article{12e9a768ee7f4a3aab3950c6b25ef47a,
title = "Corticosteroid-Free Remission vs Overall Remission in Clinical Trials of Moderate-Severe Ulcerative Colitis and Crohn's Disease",
abstract = "Background: We summarized the protocol-specified corticosteroid tapering regimens in clinical trials of moderate-severe ulcerative colitis (UC) and Crohn's disease (CD) and calculated differences in rates of clinical remission vs corticosteroid-free clinical remission (CSF-CR). Methods: Through a systematic literature review through February 28, 2019, we identified 16 randomized controlled trials (RCTs) of biologics or small molecules in patients with moderate-severe UC or CD who reported CSF-CR as an outcome. We estimated the relative risk and 95% confidence interval of achieving CSF-CR vs overall clinical remission in patients treated with active intervention or placebo through random-effects meta-analysis. Results: Across trials of UC (11 trials) and CD (5 trials), a median of 53% and 49% of participants were on corticosteroids at the time of trial entry, respectively. Participants were allowed to enter trials at a median corticosteroid dose (range) of 35 (20-40) mg/d. Doses were kept stable for a median (range) of 8 (5-10) weeks during induction therapy, after which a mandatory and structured taper was implemented, albeit with the investigators' discretion depending on clinical status. Pooled rates of CSF-CR in patients with UC and CD treated with placebo were 9.7% and 19.1%, respectively. In UC and CD trials, the rate of CSF-CR was 24% and 18% lower than the rate of overall clinical remission, respectively. Conclusions: Protocol-specified corticosteroid tapering regimens vary across trials. These findings will help to inform the design and interpretation of future clinical trials and highlight the need for standardization.",
keywords = "Crohn's disease, clinical trials, end points, maintenance therapy, ulcerative colitis",
author = "John George and Siddharth Singh and Dulai, {Parambir S.} and Christopher Ma and Tran Nguyen and Feagan, {Brian G.} and Sandborn, {William J.} and Vipul Jairath",
note = "Funding Information: Conflicts of interest: John George has no conflicts to declare. Siddharth Singh is supported by the NIDDK K23DK117058, the American College of Gastroenterology Junior Faculty Development Award, and the Crohn{\textquoteright}s and Colitis Foundation Career Development Award (#404614); has received research grant support from Pfizer and AbbVie; has received consulting fees from AbbVie, Takeda, and AMAG Pharmaceuticals; and has received honoraria from Pfizer for grant review. Parambir S. Dulai has received research grant support from Takeda, Pfizer, Janssen, Prometheus, Polymedco, and ALPCO; has served as a consultant for Takeda, Janssen, Prometheus Labs, and Abbvie. Christopher Ma has served as a consultant for Janssen, AbbVie, Pfizer, and Robarts Clinical Trials, Inc. Tran Nguyen is an employee of Robarts Clinical Trials Inc. Brian Feagan has received grant/research support from Millennium Pharmaceuticals, Merck, Tillotts Pharma, AbbVie, Novartis Pharmaceuticals, Centocor, Elan/Biogen, UCB Pharma, Bristol-Myers Squibb, Genentech, ActoGenix, and Wyeth Pharmaceuticals; has received consulting fees from Millennium Pharmaceuticals, Merck, Centocor, Elan/Biogen, Janssen-Ortho, Teva Pharmaceuticals, Bristol-Myers Squibb, Celgene, UCB Pharma, AbbVie, AstraZeneca, Serono, Genentech, Tillotts Pharma, Unity Pharmaceuticals, Albireo Pharma, Given Imaging, Salix Pharmaceuticals, Novonordisk, GSK, ActoGenix, Prometheus Therapeutics and Diagnostics, Athersys, Axcan, Gilead, Pfizer, Shire, Wyeth, Zealand Pharma, Zyngenia, GiCare Pharma, and Sigmoid Pharma; and has received speaker{\textquoteright}s bureau fees from UCB, AbbVie, and J&J/Janssen. William J. Sandborn has received research grants from Atlantic Healthcare Limited, Amgen, Genentech, Gilead Sciences, Abbvie, Janssen, Takeda, Lilly, Celgene/Receptos; has received 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, Prizer, Precision IBD, Progenity, 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, and Vivelix Pharmaceuticals; and has received stock or stock options from BeiGene, Escalier Biosciences, Gossamer Bio, Oppilan Pharma, Precision IBD, Progenity, Ritter Pharmaceuticals, Ventyx Biosciences, Vimalan Biosciences (spouse: Opthotech – consultant, stock options; Progenity – consultant, stock; Oppilan Pharma – employee, stock options; Escalier Biosciences – employee, stock options; Precision IBD – employee, stock options; Ventyx Biosciences – employee, stock options; Vimalan Biosciences – employee, stock options). Vipul Jairath receives salary support from the John and Susan McDonald Endowed IBD Chair at Western University, London, Ontario, Canada; has received consulting fees from AbbVie, Eli Lilly, GlaxoSmithKline, Arena Pharmaceuticals, Genentech, Pendopharm, Sandoz, Merck, Takeda, Janssen, Robarts Clinical Trials, Topivert, and Celltrion; and has received speaker fees from Takeda, Janssen, Shire, Ferring, AbbVie, and Pfizer. Publisher Copyright: {\textcopyright} 2020 Crohn's & Colitis Foundation. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.",
year = "2020",
month = mar,
day = "4",
doi = "10.1093/ibd/izz193",
language = "English (US)",
volume = "26",
pages = "515--523",
journal = "Inflammatory bowel diseases",
issn = "1078-0998",
publisher = "John Wiley and Sons Inc.",
number = "4",
}