Department of Medicine, Janakpuri Super Specialty Hospital, New Delhi, New Delhi, India.
Division of Gastroenterology.
Curr Opin Gastroenterol. 2022 Jul 1;38(4):337-346. doi: 10.1097/MOG.0000000000000854.
Over the last decade, there has been rapid expansion of the therapeutic armamentarium, and evolution of treatment strategies, for the management of inflammatory bowel diseases (IBDs). Consequently, there is an increasing need for head-to-head or comparative efficacy trials to inform optimal positioning of therapies, and pragmatic trials comparing treatment strategies to inform treatment approach. In this review, we will discuss the current status and future of comparative efficacy clinical trials in IBD.
Pivotal phase IIIB superiority clinical trials have demonstrated superiority of vedolizumab over adalimumab for achieving clinical remission in patients with moderate-to-severe ulcerative colitis (VARSITY) and failed to demonstrate superiority of ustekinumab over adalimumab in patients with moderate-to-severe Crohn's disease (SEAVUE). Noninferiority clinical trials of biosimilars have confirmed absence of meaningful differences in safety and efficacy of biosimilar infliximab over originator infliximab, as initial therapy or switching stable patients during maintenance. Network meta-analyses, indirect treatment comparison using patient-level data from placebo-controlled trials and real-world observational studies have inform comparative effectiveness and safety of different therapies for management of IBD.
Head-to-head clinical trials are critically important to advance the field of IBD. Comparative efficacy trials are slow and expensive to conduct, may not be broadly generalizable, and are not powered for safety events or other relevant outcomes. Alternative approaches to comparative effectiveness such as network meta-analysis and well designed real-world observational studies are able to bridge gaps in clinical practice.
在过去的十年中，炎症性肠病（IBD）的治疗手段迅速扩展，治疗策略也不断演变。因此，越来越需要进行头对头或疗效比较试验，以确定治疗方法的最佳定位，并进行比较治疗策略的实用试验，以确定治疗方法。在这篇综述中，我们将讨论 IBD 中比较疗效临床试验的现状和未来。
IIIb 期关键性优越性临床试验表明，在中重度溃疡性结肠炎患者中，vedolizumab 优于 adalimumab 达到临床缓解（VARSITY），而在中重度克罗恩病患者中，ustekinumab 并不优于 adalimumab（SEAVUE）。生物类似药的非劣效性临床试验证实，在安全性和疗效方面，生物类似药 infliximab 与原研 infliximab 没有显著差异，无论是作为初始治疗还是在维持治疗中转换稳定患者。网络荟萃分析、使用安慰剂对照试验和真实世界观察性研究的患者水平数据进行的间接治疗比较，为 IBD 管理中不同治疗方法的比较疗效和安全性提供了信息。
头对头临床试验对于推进 IBD 领域至关重要。比较疗效试验的开展既缓慢又昂贵，可能无法广泛推广，也无法为安全性事件或其他相关结局提供足够的效力。网络荟萃分析和精心设计的真实世界观察性研究等比较有效性的替代方法能够弥补临床实践中的空白。
