Comparison of treatment effect between phase 2 and phase 3 trials in patients with inflammatory bowel disease

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


Pauline Wils 1 2Vipul Jairath 3Bruce E Sands 4Fernando Magro 5Walter Reinisch 6David Rubin 7Silvio Danese 8Cédric Baumann 9Laurent 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.


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.


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