Department of Gastroenterology, Claude Huriez Hospital, University of Lille 2, Lille, France.
Inserm, CHU Lille, U1286- INFINITE- Institute for Translational Research in Inflammation, University of Lille, Lille, France.
United European Gastroenterol J. 2023 Oct;11(8):797-806. doi: 10.1002/ueg2.12455. Epub 2023 Sep 5.
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.
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.
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.
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.
炎症性肠病领域积累了多项随机对照试验，为比较 2 期和 3 期试验的治疗效果提供了机会。我们旨在确定在研究生物制剂和小分子药物的 3 期试验中观察到的治疗效果是否与之前的 2 期试验不同。
我们首先对纳入溃疡性结肠炎（UC）或克罗恩病（CD）患者的 2 期和 3 期试验进行了综述。我们比较了各期主要终点的总体成功率（多个 3 期试验可与单个 2 期试验匹配）。然后，我们比较了匹配的 2 期和 3 期试验的总体成功率（比例为 1:1），并进行了敏感性分析。
我们确定了 14 项 2 期（8 项 CD；6 项 UC）和 24 项 3 期（13 项 CD；11 项 UC）试验。在 CD 中，不同的分析表明，临床缓解和临床反应的总体成功率在 2 期试验中显著高于 3 期试验。在 UC 中，分析表明，临床缓解、临床反应和组织学结局之间的治疗效果百分比在各期之间似乎相似，但内镜结局的 2 期试验的总体成功率低于 3 期试验。
在 UC 中，我们观察到 2 期和 3 期试验之间临床和组织学结局的治疗效果百分比相似，但内镜结局则不然。而在 CD 中，我们显示出各期之间无法复制相似的结果。这些结果可能有助于赞助商设计未来的药物开发计划。
