United European Gastroenterol J. 2023 Oct;11(8):797-806. doi: 10.1002/ueg2.12455.Epub 2023 Sep 5.

Pauline Wils ^1 2, Vipul Jairath ³, Bruce E Sands ⁴, Fernando Magro ⁵, Walter Reinisch ⁶, David Rubin ⁷, Silvio Danese ⁸, Cédric Baumann ⁹, Laurent Peyrin-Biroulet ^10 11

Author information

¹Department of Gastroenterology, Claude Huriez Hospital, University of Lille 2, Lille, France.

²Inserm, CHU Lille, U1286- INFINITE- Institute for Translational Research in Inflammation, University of Lille, Lille, France.

³Division of Gastroenterology, Department of Medicine, Western University, London, Ontario, Canada.

⁴The Dr Henry J Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

⁵Department of Gastroenterology, Centro Hospitalar São João, Porto, Portugal.

⁶Division Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.

⁷Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, Illinois, USA.

⁸Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy.

⁹Unit of Methodology, Data Management and Statistic, Nancy University Hospital, Nancy, France.

¹⁰Department of Gastroenterology, CHRU-Nancy, University of Lorraine, Nancy, France.

¹¹Inserm, NGERE, University of Lorraine, Nancy, France.

Abstract

Background and aims: The accumulation of multiple randomized controlled trials in the field of inflammatory bowel diseases provides an opportunity to compare treatment effects between phase 2 and 3 trials. We aimed to determine whether treatment effects observed in phase 3 investigating biologics and small molecule drugs differed from those in their preceding phase 2 trial.

Methods: We first performed a review of phase 2 and phase 3 trials enrolling ulcerative colitis (UC) or Crohn's disease (CD) patients. We compared the percent overall success for key endpoints between phases (several phase 3 could be matched to a single phase 2 trial). Then, we compared the percent overall success in the matched phase 2 and 3 trials (ratio 1:1), and performed sensitivity analysis.

Results: We identified 14 phase 2 (8 CD; 6 UC) and 24 phase 3 (13 CD; 11 UC) trials. In CD, the different analyses suggest that the percentage of overall success of clinical remission and clinical response was significantly higher in phase 2 than in phase 3 trials. In UC, the analyses suggest collectively that the percent of treatment effect seemed similar for clinical remission, clinical response and histologic outcomes between phases but with a lower percentage of overall success in phase 2 than in phase 3 trials for endoscopic endpoints.

Conclusions: In UC, we observed a similar percentage of treatment effect for clinical and histologic outcomes between phase 2 and 3 trials but not for endoscopic outcomes. Whereas in CD, we showed a failure to reproduce similar results between phases. These results may help sponsors in the design of future drug development programs.