编者：韩青，西京医院临床免疫科

目  的

比较不同剂量托法替尼的疗效和安全性，托法替尼是一种口服的Janus激酶抑制剂，同安慰剂应用于活动性AS(包括AS及ax-SpA)。

方  法

在这16周(12周治疗，4周筛选)Ⅱ期多中心剂量范围的试验中，处于疾病活动期的成人AS患者(分别N=51，52，52，52)为安慰剂或托法替尼每天2，5或10mg，2/d。第12周，主要疗效终点是对ASAS20反应率的评估，次要终点包括疾病活动度、病人临床结果及骶髂关节、脊柱的MRI。同时进行安全监测。

结  果

Emax模型分析主要终点显示，每天10mg托法替尼2/d，ASAS20反应率为67.4%，比安慰剂组高27.3%。支持性的常规近似分析显示，托法替尼5mg2/d的ASAS20反应率比安慰剂组高2倍(80.8%，41.2%;p<0.001);每天两次2mg和10mg的托法替尼ASAS20反应比安慰剂组反应率更高(分别为51.9%和55.8%;无统计学差异)。次要终点结果显示，每天5mg和10mg托法替尼2/d比安慰剂组更有效果。MRI结果显示明确的剂量反应关系。在治疗组中，不良事件相似，没有意外的安全发现。

结  论

每天两次5mg和10mg的托法替尼临床疗效与安慰剂相比，在减轻成人活动性AS患者症状和观察终点方面的效果更明显，与其他为期12周研究结果一致。

参考文献：

Tofacitinib in patients with ankylosingspondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-rangingstudy

Désirée van der Heijde. et al

ABSTRACT

Objectives

Tocompare efficacy and safety of various doses of tofacitinib, an oral Januskinase inhibitor, with placebo in patients with active ankylosing spondylitis(AS, radiographic axial spondyloarthritis).

Methods

Inthis 16-week (12-week treatment, 4-week washout), phase II, multicentre,dose-ranging trial, adult patients with active AS were randomised (N=51, 52,52, 52, respectively) to placebo or tofacitinib 2, 5 or 10 mg twice daily. Theprimary efficacy endpoint was Assessment of SpondyloArthritis InternationalSociety 20% improvement (ASAS20) response rate at week 12. Secondary endpointsincluded objective measures of disease activity, patient-reported outcomes andMRI of sacroiliac joints and spine. Safety was monitored.

Results

Emaxmodel analysis of the primary endpoint predicted a tofacitinib 10 mg twicedaily ASAS20 response rate of 67.4%, 27.3% higher than placebo. Supportivenormal approximation analysis demonstrated tofacitinib 5 mg twice daily ASAS20response rate significantly higher than placebo (80.8% vs 41.2%; p<0.001);tofacitinib 2 and 10 mg twice daily demonstrated greater response rate thanplacebo (51.9% and 55.8%, respectively; not significant). Secondary endpointsgenerally demonstrated greater improvements with tofacitinib 5 and 10 mg twicedaily than placebo. Objective (including MRI) endpoints demonstrated clear doseresponse. Adverse events were similar across treatment groups with no unexpectedsafety findings. Dose-dependent laboratory outcome changes returned close tobaseline by week 16.

Conclusions

Tofacitinib5 and 10 mg twice daily demonstrated greater clinical efficacy versus placeboin reducing signs, symptoms and objective endpoints of active AS in adultpatients with a similar 12-week safety profile as reported in otherindications.

AnnRheumDis.2017Aug;76(8):1340-1347.doi: 10.1136/annrheumdis-2016-210322.Epub 2017 Jan 27.