维也纳医科大Daniel Aletaha课题组发布了关于风湿病2期和3期疗效的随机对照试验结果。2020年4月20日出版的《自然-医学》在线发表了这项成果。

研究人员通过一项系统的荟萃分析开展了针对风湿性关节炎和银屑病靶向治疗抗风湿药物的随机对照、双盲试验。通过混合模型逻辑回归比较了美国风湿病学会（ACR）20响应的主要结果，并探索了功效高估的潜在决定因素。

在类风湿关节炎中，二期试验的结果系统性地高估了随后的三期试验结果（较二期与三期ACR20的比值比：1.39，95％置信区间：1.25-1.57，P<0.001）。银屑病关节炎试验的数据与之相似，但无统计学意义（二期与三期ACR20的比值比：1.35，95％置信区间：0.94-1.94，P = 0.09）。

纳入标准的差异很大程度上解释了观察到的功效差异。该发现对新疗法开发和测试中的所有利益相关者都有潜在的影响，以及潜在的道德影响。

据悉，3期试验是药物开发药物的主要阶段，通常不能达到2期研究前所设定的预期。

附：英文原文

Title: Efficacy outcomes in phase 2 and phase 3 randomized controlled trials in rheumatology

Author: Andreas Kerschbaumer, Josef S. Smolen, Harald Herkner, Tijen Stefanova, Eva Chwala, Daniel Aletaha

Issue&Volume: 2020-04-20

Abstract: Phase 3 trials are the mainstay of drug development across medicine but have often not met expectations set by preceding phase 2 studies. A systematic meta-analysis evaluated all randomized controlled, double-blind trials investigating targeted disease-modifying anti-rheumatic drugs in rheumatoid and psoriatic arthritis. Primary outcomes of American College of Rheumatology (ACR) 20 responses were compared by mixed-model logistic regression, including exploration of potential determinants of efficacy overestimation. In rheumatoid arthritis, phase 2 trial outcomes systematically overestimated subsequent phase 3 results (odds ratio comparing ACR20 in phase 2 versus phase 3: 1.39, 95% confidence interval: 1.25–1.57, P<0.001). Data for psoriatic arthritis trials were similar, but not statistically significant (odds ratio comparing ACR20 in phase 2 versus phase 3: 1.35, 95% confidence interval: 0.94–1.94, P=0.09). Differences in inclusion criteria largely explained the observed differences in efficacy findings. Our findings have implications for all stakeholders in new therapeutic development and testing, as well as potential ethical implications.

DOI: 10.1038/s41591-020-0833-4

Source: https://www.nature.com/articles/s41591-020-0833-4