托法替布（CP-690,550）用于接受甲氨蝶呤治疗的类风湿关节炎患者：一项为期24个月的III期随机影像学研究的12个月数据。

Tofacitinib (CP-690,550) in patients with rheumatoid arthritis receiving methotrexate: twelve-month data from a twenty-four-month phase III randomized radiographic study.

作者信息

van der Heijde Désirée, Tanaka Yoshiya, Fleischmann Roy, Keystone Edward, Kremer Joel, Zerbini Cristiano, Cardiel Mario H, Cohen Stanley, Nash Peter, Song Yeong-Wook, Tegzová Dana, Wyman Bradley T, Gruben David, Benda Birgitta, Wallenstein Gene, Krishnaswami Sriram, Zwillich Samuel H, Bradley John D, Connell Carol A

机构信息

Leiden University Medical Center, Leiden, The Netherlands.

出版信息

Arthritis Rheum. 2013 Mar;65(3):559-70. doi: 10.1002/art.37816.

DOI:10.1002/art.37816

PMID:23348607

Abstract

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.

摘要

目的

这项为期24个月的III期研究旨在考察托法替布对甲氨蝶呤（MTX）反应不足的类风湿关节炎（RA）患者的结构保护作用。本文报告了计划中的12个月中期分析的数据。

方法

在这项双盲、平行组、安慰剂对照研究中，接受背景MTX治疗的患者按4:4:1:1随机分组，分别接受每日两次5 mg托法替布、每日两次10 mg托法替布、安慰剂加每日两次5 mg托法替布以及安慰剂加每日两次10 mg托法替布治疗。在第3个月时，对无反应的安慰剂治疗患者进行盲法升级，使其按上述方案接受托法替布治疗；其余安慰剂治疗患者在第6个月时升级。对四个主要疗效终点均采用逐步下调程序进行分析。

结果

在第6个月时，根据美国风湿病学会20%改善标准，每日两次5 mg和10 mg托法替布的缓解率高于安慰剂（分别为51.5%和61.8%，而安慰剂为25.3%；P均<0.0001）。在第6个月时，每日两次5 mg和10 mg托法替布的总改良Sharp/van der Heijde评分的最小二乘均值（LSM）变化分别为0.12和0.06，而安慰剂为0.47（分别为P = 0.0792和P≤0.05）。在第3个月时，每日两次5 mg和10 mg托法替布的健康评估问卷残疾指数评分的LSM变化分别为-0.40（因逐步下调程序未声明显著性）和-0.54（P<0.0001），而安慰剂为-0.15。在第6个月时，每日两次5 mg和10 mg托法替布的缓解率（定义为使用红细胞沉降率的28个关节的4变量疾病活动评分<2.6）分别为7.2%（因逐步下调程序未声明显著性）和16.0%（P<0.0001），而安慰剂为1.6%。安全性概况与既往研究结果一致。