Hanžel Jurij, Solitano Virginia, Vuyyuru Sudheer Kumar, Panaccione Remo, Sands Bruce E, Peyrin-Biroulet Laurent, Danese Silvio, D'Haens Geert R, Atreya Raja, Allez Matthieu, Bernstein Charles N, Bossuyt Peter, Bressler Brian, Bryant Robert V, Cohen Benjamin L, Colombel Jean-Frederic, D'Amico Ferdinando, Dignass Axel, Dubinsky Marla, Fleshner Phillip, Gearry Richard B, Hanauer Stephen B, Hart Ailsa L, Kayal Maia, Kucharzik Torsten, Lakatos Peter L, Louis Edouard, Magro Fernando, Narula Neeraj, Leong Rupert W, Panés Julián, Raine Tim, Ran Zhihua, Regueiro Miguel D, Reinisch Walter, Singh Siddharth, Steinhart A Hillary, Travis Simon, Ungaro Ryan C, van der Woude C Janneke, Yamamoto Takayuki, Ahuja Vineet, Rubin David T, Dulai Parambir S, Cornfield Linda J, Hogan Malcolm, Sandborn William J, Feagan Brian G, Jairath Vipul, Ma Christopher
Department of Gastroenterology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; Alimentiv Inc, London, Ontario, Canada.
Division of Gastroenterology, Department of Medicine, Western University, London, Ontario, Canada; Division of Gastroenterology and Gastrointestinal Endoscopy, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale San Raffaele, Università Vita-Salute San Raffaele, Milan, Italy.
Gastroenterology. 2025 May 28. doi: 10.1053/j.gastro.2025.05.015.
BACKGROUND & AIMS: Approval of new therapies for inflammatory bowel disease (IBD) requires rigorously designed and well-executed randomized controlled trials (RCTs). Corticosteroids remain a cornerstone of IBD induction therapy, and many patients in trials are enrolled while taking corticosteroids. Despite this, approaches to corticosteroid management in RCTs have been highly heterogeneous, often differing from clinical practice. This negatively impacts patients' willingness to participate due to prolonged corticosteroid exposure and may potentially bias outcomes in the clinical trial. Our aim is to provide comprehensive standardized recommendations on key aspects of corticosteroid use in IBD clinical trials through a multiphase, international expert consensus, with a goal to help inform and standardize practice in future RCTs.
The consensus was informed by a systematic review of MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, which determined the corticosteroid management rules used in placebo-controlled trials of advanced therapies in IBD. International expert consensus recommendations for all aspects of corticosteroid management in RCTs were then developed using a modified Delphi process with 2 rounds of survey questions and a ratification meeting.
These recommendations propose management of corticosteroids during screening, induction, and maintenance phases of pharmacologic trials in IBD and define corticosteroid-related end points. We emphasize the need for minimizing corticosteroid exposure through expedited tapering and shorter fixed-dosing periods that more closely reflect clinical care and provide recommendations for standardized definitions of corticosteroid-free remission.
These recommendations will serve to optimize trial design and facilitate appropriate, acceptable, and standardized RCT corticosteroid handling practices.
批准用于炎症性肠病（IBD）的新疗法需要设计严谨且执行良好的随机对照试验（RCT）。皮质类固醇仍然是IBD诱导治疗的基石，许多试验中的患者在服用皮质类固醇时被纳入研究。尽管如此，RCT中皮质类固醇管理方法高度异质，往往与临床实践不同。这因皮质类固醇暴露时间延长而对患者参与意愿产生负面影响，并可能在临床试验中使结果产生偏差。我们的目标是通过多阶段的国际专家共识，就IBD临床试验中皮质类固醇使用的关键方面提供全面的标准化建议，以帮助为未来的RCT提供信息并规范实践。
通过对MEDLINE、Embase和Cochrane对照试验中央注册库的系统评价为该共识提供依据，该评价确定了IBD中晚期疗法的安慰剂对照试验中使用的皮质类固醇管理规则。然后使用改良的德尔菲法，通过两轮调查问卷和一次批准会议，制定了RCT中皮质类固醇管理各方面的国际专家共识建议。
这些建议提出了IBD药物试验筛查、诱导和维持阶段皮质类固醇的管理方法，并定义了与皮质类固醇相关的终点。我们强调需要通过加速减量和更短的固定给药期来尽量减少皮质类固醇暴露，这更贴近临床护理，并为无皮质类固醇缓解的标准化定义提供建议。
这些建议将有助于优化试验设计，并促进适当、可接受和标准化的RCT皮质类固醇处理实践。
