n International Consensus on Appropriate Management of Corticosteroids in Clinical Trials in Inflammatory Bowel Disease.
Hanžel J., Solitano V., Vuyyuru SK., Panaccione R., Sands BE., Peyrin-Biroulet L., Danese S., D'Haens GR., Atreya R., Allez M., Bernstein CN., Bossuyt P., Bressler B., Bryant RV., Cohen BL., Colombel J-F., D'Amico F., Dignass A., Dubinsky M., Fleshner P., Gearry RB., Hanauer SB., Hart AL., Kayal M., Kucharzik T., Lakatos PL., Louis E., Magro F., Narula N., Leong RW., Panés J., Raine T., Ran Z., Regueiro MD., Reinisch W., Singh S., Steinhart AH., Travis S., Ungaro RC., van der Woude CJ., Yamamoto T., Ahuja V., Rubin DT., Dulai PS., Cornfield LJ., Hogan M., Sandborn WJ., Feagan BG., Jairath V., Ma C.
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. METHODS: 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. RESULTS: 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. CONCLUSIONS: These recommendations will serve to optimize trial design and facilitate appropriate, acceptable, and standardized RCT corticosteroid handling practices.