日本类风湿关节炎患者中改良释放与即刻释放托法替布的比较：一项随机、III 期、非劣效性研究。

Modified- versus immediate-release tofacitinib in Japanese rheumatoid arthritis patients: a randomized, phase III, non-inferiority study.

机构信息

The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.

Pfizer Japan Inc, Tokyo, Japan.

出版信息

Rheumatology (Oxford). 2019 Jan 1;58(1):70-79. doi: 10.1093/rheumatology/key250.

OBJECTIVE

Tofacitinib is an oral Janus kinase inhibitor for treatment of RA. We compared tofacitinib modified-release (MR) 11 mg once daily (QD) with tofacitinib immediate-release (IR) 5 mg twice daily (BID) in Japanese patients with RA and inadequate response to MTX.

METHODS

Phase III, randomized, double-blind, double-dummy, 12-week study. Patients were randomized to tofacitinib MR 11 mg QD (n = 104) or IR 5 mg BID (n = 105), with stable MTX. Compliance was based on returned pill counts. The primary objective was to demonstrate non-inferiority of MR 11 mg QD to IR 5 mg BID. Non-inferiority was declared if the upper bound of the two-sided 95% CI for the difference in change from baseline in DAS28-4(CRP) at week 12 was <0.6.

RESULTS

At week 12, with tofacitinib MR 11 mg QD and IR 5 mg BID, respectively, the change from baseline in least squares mean DAS28-4(CRP) was -2.43 and -2.85; the mean difference was 0.43 (95% CI 0.17, 0.69). Non-inferiority of MR 11 mg QD to IR 5 mg BID was not met. Improvement of DAS28-4(CRP) ⩾1.2 was observed in 89 and 85% of patients, respectively, corresponding to a clinically important, significant change in both groups. The frequency of adverse events (52.9 and 51.4%, respectively) and serious adverse events (4.8 and 3.8%, respectively) was generally similar between treatments. No deaths were reported.

CONCLUSION

Non-inferiority of MR 11 mg QD to IR 5 mg BID was not met in this study. However, clinically meaningful improvements in RA were observed with both tofacitinib formulations in Japanese patients. The safety profile was similar with both formulations.

TRIAL REGISTRATION

ClinicalTrials.gov, http://clinicaltrials.gov, NCT02281552.

目的

托法替布是一种用于治疗类风湿关节炎的口服 Janus 激酶抑制剂。我们比较了托法替布缓释片（MR）11 毫克每日一次（QD）与托法替布速释片（IR）5 毫克每日两次（BID）在对甲氨蝶呤反应不足的日本类风湿关节炎患者中的疗效。

方法

这是一项为期 12 周的 III 期、随机、双盲、双模拟、对照研究。患者被随机分配至托法替布 MR 11 毫克 QD（n = 104）或 IR 5 毫克 BID（n = 105）组，同时接受稳定剂量的甲氨蝶呤治疗。依从性基于返还的药丸计数。主要目的是证明 MR 11 毫克 QD 与 IR 5 毫克 BID 相比非劣效。如果第 12 周时 DAS28-4（CRP）自基线变化的双侧 95%置信区间上限<0.6，则宣布非劣效。

结果

在第 12 周，托法替布 MR 11 毫克 QD 和 IR 5 毫克 BID 组自基线的最小二乘均数 DAS28-4（CRP）变化分别为-2.43 和-2.85；平均差异为 0.43（95%CI 0.17,0.69）。MR 11 毫克 QD 与 IR 5 毫克 BID 相比非劣效性未得到满足。分别有 89%和 85%的患者 DAS28-4（CRP）改善≥1.2，两组均有显著的临床重要变化。不良反应的发生率（分别为 52.9%和 51.4%）和严重不良反应的发生率（分别为 4.8%和 3.8%）在两种治疗方案中大致相似。没有死亡报告。