A&R: 接受甲氨蝶呤治疗的类风湿关节炎患者合用Tofacitinib（CP-690,550）的临床随机研究

来自荷兰莱顿大学医学中心的Desiree van der Heijde等人进行了一项研究，该项为期24周的三期研究的目的是检验Tofacitinib对甲氨蝶呤（MTX）疗效不佳的类风湿关节炎（RA）患者的关节结构的保护的作用。数据来源于第12周的中期分析报告。研究结果在线发布在2013年3月的ARTHRITIS & RHEUMATISM（关节炎与风湿病）上。研究者发现，接受MTX治疗的RA患者，合用tofacitinib能抑制关节结构破坏，并降低疾病活动度。

研究者进行了一项双盲，平行，安慰剂对照的研究，接受背景MTX治疗的患者随机分组为4:4:1:1，分别接受如下治疗：tofacitinib 5mg 每天两次、tofacitinib 10mg 每天两次、tofacitinib的安慰剂 5mg 每天两次或placebo的安慰剂 10mg 每天两次。在3个月时，接受安慰剂治疗的无反应患者以盲态升级为上述的tofacitinib治疗，剩余的接受安慰剂治疗的患者继续安慰剂治疗6个月。以递减的过程分析四个主要疗效终点。

研究结果如下，在6个月时，依据美国大学风湿病协会20 ％改善标准，tofacitinib 5mg 每日两次和tofacitinib 10mg 每日两次组的缓解率高于安慰剂组（分别是51.5%和61.8% vs 25.3%，p均<0.0001）。在6个月时，tofacitinib 5mg 每天两次和tofacitinib 10mg 每天两次组的修订总Sharp/van der Heijde评分的最小二乘均数（LSM）的变化分别是0.12和0.06，vs 0.47（安慰剂组）（分别是P=0.079，P < 0.05）。在3个月时，tofacitinib 5mg 每天两次和tofacitinib 10mg 每天两次组的健康调查问卷残疾指数积分的LSM变化分别是-0.40（以递减过程显著性未宣布）和-0.54（P < 0.0001），vs -0.15（安慰剂组）。在6个月时，tofacitinib 5mg 每天两次和tofacitinib 10mg 每天两次组的缓解率（依据包括血沉的28个关节的四个变量的疾病活动积分<2.6 ）分别是7.2%（以递减过程显著性未宣布）和16%（P < 0.0001）。安全性和以前的研究结果一致。

研究发现，来自12月的中期分析数据证实，接受MTX治疗的RA患者，合用tofacitinib能抑制关节结构破坏，并降低疾病活动度。

与类风湿相关的拓展阅读：

• ARD：紫外线暴露可减少女性罹患类风湿关节炎风险
• Ann Rheum Dis：日光浴或预防类风湿关节炎
• Rheumatology：类风湿关节炎患者整体肿瘤罹患风险高
• Lancet：依那西普维持治疗可控制类风湿关节炎疾病活动
• Arthritis Rheum：类风湿关节炎患者 THA后易脱臼，TKA后易感染
• FDA批准第一个治疗类风湿关节炎口服生物制剂Xeljanz 更多信息请点击：有关类风湿更多资讯

Tofacitinib (CP-690,550) in patients with rheumatoid arthritis receiving methotrexate: twelve-month data from a twenty-four-month phase III randomized radiographic study.
OBJECTIVE
The purpose of this 24-month phase III study was to examine structural preservation with tofacitinib in patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX). Data from a planned 12-month interim analysis are reported.
METHODS
In this double-blind, parallel-group, placebo-controlled study, patients receiving background MTX were randomized 4:4:1:1 to tofacitinib at 5 mg twice daily, tofacitinib at 10 mg twice daily, placebo to tofacitinib at 5 mg twice daily, and placebo to tofacitinib at 10 mg twice daily. At month 3, nonresponder placebo-treated patients were advanced in a blinded manner to receive tofacitinib as indicated above; remaining placebo-treated patients were advanced at 6 months. Four primary efficacy end points were all analyzed in a step-down procedure.
RESULTS
At month 6, response rates according to the American College of Rheumatology 20% improvement criteria for tofacitinib at 5 mg and 10 mg twice daily were higher than those for placebo (51.5% and 61.8%, respectively, versus 25.3%; both P < 0.0001). At month 6, least squares mean (LSM) changes in total modified Sharp/van der Heijde score for tofacitinib at 5 mg and 10 mg twice daily were 0.12 and 0.06, respectively, versus 0.47 for placebo (P = 0.0792 and P ≤ 0.05, respectively). At month 3, LSM changes in the Health Assessment Questionnaire disability index score for tofacitinib at 5 mg and 10 mg twice daily were -0.40 (significance not declared due to step-down procedure) and -0.54 (P < 0.0001), respectively, versus -0.15 for placebo. At month 6, rates of remission (defined as a value <2.6 for the 4-variable Disease Activity Score in 28 joints using the erythrocyte sedimentation rate) for tofacitinib at 5 mg and 10 mg twice daily were 7.2% (significance not declared due to step-down procedure) and 16.0% (P < 0.0001), respectively, versus 1.6% for placebo. The safety profile was consistent with findings in previous studies.
CONCLUSION
Data from this 12-month interim analysis demonstrate that tofacitinib inhibits progression of structural damage and improves disease activity in patients with RA who are receiving MTX.