托法替布治疗强直性脊柱炎：一项III期随机双盲安慰剂对照研究。
Tofacitinib for the treatment of ankylosing spondylitis: a phase III, randomised, double-blind, placebo-controlled study.
作者信息
Deodhar Atul, Sliwinska-Stanczyk Paula, Xu Huji, Baraliakos Xenofon, Gensler Lianne S, Fleishaker Dona, Wang Lisy, Wu Joseph, Menon Sujatha, Wang Cunshan, Dina Oluwaseyi, Fallon Lara, Kanik Keith S, van der Heijde Désirée
机构信息
Division of Arthritis and Rheumatic Diseases, Oregon Health & Science University, Portland, Oregon, USA
Department of Rheumatology, Reumatika Centrum Reumatologii, Warsaw, Poland.
出版信息
Ann Rheum Dis. 2021 Aug;80(8):1004-1013. doi: 10.1136/annrheumdis-2020-219601. Epub 2021 Apr 27.
OBJECTIVE
To assess the efficacy/safety of tofacitinib in adult patients with active ankylosing spondylitis (AS).
METHODS
This phase III, randomised, double-blind, placebo-controlled study enrolled patients aged ≥18 years diagnosed with active AS, meeting the modified New York criteria, with centrally read radiographs, and an inadequate response or intolerance to ≥2 non-steroidal anti-inflammatory drugs. Patients were randomised 1:1 to receive tofacitinib 5 mg two times per day or placebo for 16 weeks. After week 16, all patients received open-label tofacitinib until week 48. The primary and key secondary endpoints were Assessment of SpondyloArthritis international Society ≥20% improvement (ASAS20) and ≥40% improvement (ASAS40) responses, respectively, at week 16. Safety was assessed throughout.
RESULTS
269 patients were randomised and treated: tofacitinib, n=133; placebo, n=136. At week 16, the ASAS20 response rate was significantly (p<0.0001) greater with tofacitinib (56.4%, 75 of 133) versus placebo (29.4%, 40 of 136), and the ASAS40 response rate was significantly (p<0.0001) greater with tofacitinib (40.6%, 54 of 133) versus placebo (12.5%, 17 of 136). Up to week 16, with tofacitinib and placebo, respectively, 73 of 133 (54.9%) and 70 of 136 (51.5%) patients had adverse events; 2 of 133 (1.5%) and 1 of 136 (0.7%) had serious adverse events. Up to week 48, with tofacitinib, 3 of 133 (2.3%) patients had adjudicated hepatic events, 3 of 133 (2.3%) had non-serious herpes zoster, and 1 of 133 (0.8%) had a serious infection; with placebo→tofacitinib, 2 (1.5%) patients had non-serious herpes zoster. There were no deaths, malignancies, major adverse cardiovascular events, thromboembolic events or opportunistic infections.
CONCLUSIONS
In adults with active AS, tofacitinib demonstrated significantly greater efficacy versus placebo. No new potential safety risks were identified.
TRIAL REGISTRATION NUMBER
NCT03502616.
目的
评估托法替布在成年活动性强直性脊柱炎（AS）患者中的疗效/安全性。
方法
这项III期随机双盲安慰剂对照研究纳入了年龄≥18岁、诊断为活动性AS且符合改良纽约标准、经中心阅片，对≥2种非甾体抗炎药反应不佳或不耐受的患者。患者按1:1随机分组，接受每日2次托法替布5mg或安慰剂治疗16周。16周后，所有患者接受开放标签的托法替布治疗至48周。主要和关键次要终点分别为第16周时国际脊柱关节炎协会评估的改善≥20%（ASAS20）和改善≥40%（ASAS40）反应。全程评估安全性。
结果
269例患者被随机分组并接受治疗：托法替布组，n = 133；安慰剂组，n = 136。在第16周时，托法替布组（56.4%，133例中的75例）的ASAS20反应率显著高于安慰剂组（29.4%，136例中的40例）（p<0.0001），托法替布组（40.6%，133例中的54例）的ASAS40反应率显著高于安慰剂组（12.5%，136例中的17例）（p<0.0001）。至第16周时分别使用托法替布和安慰剂治疗，133例中的73例（54.9%）和136例中的70例（51.5%）患者发生不良事件；133例中的2例（1.5%）和136例中的1例（0.7%）发生严重不良事件。至第48周时，托法替布组133例中的3例（2.3%）患者经判定发生肝脏事件，133例中的3例（2.3%）发生非严重带状疱疹，133例中的1例（0.8%）发生严重感染；从安慰剂转用托法替布组有2例（1.5%）患者发生非严重带状疱疹。未发生死亡、恶性肿瘤、主要不良心血管事件、血栓栓塞事件或机会性感染。
结论
在成年活动性AS患者中，托法替布的疗效显著优于安慰剂。未发现新的潜在安全风险。
试验注册号
NCT03502616。
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