Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study.
Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study.
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DOI：
10.1136/annrheumdis-2016-210322
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发表时间：
2017-08
影响因子：
27.4
通讯作者：
Kanik KS
中科院分区：
文献类型：
--
作者：
van der Heijde D;Deodhar A;Wei JC;Drescher E;Fleishaker D;Hendrikx T;Li D;Menon S;Kanik KS
比较不同剂量托法替尼（一种口服Janus激酶抑制剂）与安慰剂在活动性强直性脊柱炎（AS，放射学中轴性脊柱关节炎）患者中的疗效和安全性。在这项为期16周（12周治疗，4周洗脱）、II期、多中心、剂量范围探索试验中，活动性AS成人患者被随机分配（N=51、52、52、52）至安慰剂组或托法替布2、5或10 mg每日两次组。 主要疗效终点为第12周时脊柱关节炎国际协会20%改善（ASAS 20）缓解率评估。次要终点包括疾病活动的客观指标、患者报告的结局以及骶髂关节和脊柱的MRI。监测安全性。主要终点的Emax模型分析预测托法替布10 mg每日两次的ASAS 20缓解率为67.4%，比安慰剂高27.3%。 支持性正态近似分析表明，托法替布5 mg每日2次的ASAS 20缓解率显著高于安慰剂（80.8% vs 41.2%; p<0.001）;托法替布2 mg和10 mg每日2次的缓解率高于安慰剂（分别为51.9%和55.8%;不显著）。 次要终点通常显示托法替布5 mg和10 mg每日两次的改善大于安慰剂。 客观（包括MRI）终点证明了明确的剂量反应。各治疗组的不良事件相似，无非预期安全性结果。到第16周，剂量依赖性实验室结局变化恢复至接近基线。托法替布5 mg和10 mg每日两次在减少成人患者活动性AS的体征、症状和客观终点方面的临床疗效优于安慰剂，12周安全性特征与其他适应症中报告的相似。 NCT 01786668。
To compare efficacy and safety of various doses of tofacitinib, an oral Janus kinase inhibitor, with placebo in patients with active ankylosing spondylitis (AS, radiographic axial spondyloarthritis). In this 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. The primary efficacy endpoint was Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) response rate at week 12. Secondary endpoints included objective measures of disease activity, patient-reported outcomes and MRI of sacroiliac joints and spine. Safety was monitored. Emax model analysis of the primary endpoint predicted a tofacitinib 10 mg twice daily ASAS20 response rate of 67.4%, 27.3% higher than placebo. Supportive normal approximation analysis demonstrated tofacitinib 5 mg twice daily ASAS20 response rate significantly higher than placebo (80.8% vs 41.2%; p<0.001); tofacitinib 2 and 10 mg twice daily demonstrated greater response rate than placebo (51.9% and 55.8%, respectively; not significant). Secondary endpoints generally demonstrated greater improvements with tofacitinib 5 and 10 mg twice daily than placebo. Objective (including MRI) endpoints demonstrated clear dose response. Adverse events were similar across treatment groups with no unexpected safety findings. Dose-dependent laboratory outcome changes returned close to baseline by week 16. Tofacitinib 5 and 10 mg twice daily demonstrated greater clinical efficacy versus placebo in reducing signs, symptoms and objective endpoints of active AS in adult patients with a similar 12-week safety profile as reported in other indications. NCT01786668.
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影响因子：
158.5
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