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

• Published in: United European gastroenterology journal Vol. 11; no. 8; pp. 797 - 806
• Main Authors: Wils, Pauline, Jairath, Vipul, Sands, Bruce E., Magro, Fernando, Reinisch, Walter, Rubin, David, Danese, Silvio, Baumann, Cédric, Peyrin‐Biroulet, Laurent
• Format: Journal Article
• Language: English
• Published: Nijmegen John Wiley & Sons, Inc 01.10.2023; John Wiley and Sons Inc
• Subjects: Biological products; Clinical trials; Costs; Crohns disease; Drug development; Drug dosages; Endoscopy; Inflammatory Bowel Disease; Original; Patients; Quality of life; Remission (Medicine); Success
• ISSN: 2050-6406; 2050-6414
• DOI: 10.1002/ueg2.12455

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.