Treatment options for the medical management of inflammatory bowel disease (IBD) have expanded substantially over the past decade. Multiple classes of advanced therapies, including both monoclonal antibodies and novel oral small molecules, are now available for the treatment of moderately-to-severely active Crohn’s disease and ulcerative colitis, highlighted by the approvals of the first IL23p19 antagonists, selective Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators. These advances have been accompanied by the identification of novel targets and the rapid growth in both the number and size of IBD clinical trials. Over a dozen landmark randomized controlled trials (RCTs) have been completed in the past 5 years, including the first head-to-head biologic trials, the first combination biologic studies, and multiple phase III registrational trials of novel compounds with new co-primary and composite end points that will change the treatment landscape for years to come. Importantly, the methodology of RCTs in IBD has evolved substantially, with new trial designs, evaluation of unique patient populations, and different types of efficacy and safety end points being key innovations. In this Review, we provide a comprehensive evaluation of how modern RCTs of IBD medical therapies have evolved and the implications for their appraisal that will help guide the application of these data to clinical practice.

在过去十年中，炎症性肠病 （IBD） 的药物治疗选择已大大扩展。包括单克隆抗体和新型口服小分子在内的多类先进疗法现在可用于治疗中度至重度活动性克罗恩病和溃疡性结肠炎，其中首批 IL23p19 拮抗剂、选择性 Janus 激酶抑制剂和鞘氨醇-1-磷酸受体调节剂的批准就是其中的亮点。这些进步伴随着新靶点的确定以及 IBD 临床试验数量和规模的快速增长。在过去 5 年中，已经完成了十多项具有里程碑意义的随机对照试验 （RCT），包括第一次头对头生物试验、第一次联合生物研究以及具有新的共同主要和复合终点的新型化合物的多项 III 期注册试验，这些试验将改变未来几年的治疗格局。重要的是，IBD 的 RCT 方法学已经发生了重大变化，新的试验设计、对独特患者群体的评估以及不同类型的疗效和安全性终点是关键创新。在本综述中，我们对 IBD 药物治疗的现代 RCT 如何发展及其评估的影响进行了全面评估，这将有助于指导这些数据在临床实践中的应用。