在对甲氨蝶呤应答不足的类风湿关节炎患者中，培非替尼（ASP015K）的疗效和安全性：日本一项 III 期随机、双盲、安慰剂对照试验（RAJ4）的结果。

Efficacy and safety of peficitinib (ASP015K) in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase III randomised, double-blind, placebo-controlled trial (RAJ4) in Japan.

机构信息

Keio University School of Medicine, Tokyo, Japan

University of Occupational and Environmental Health Japan, Kitakyushu, Japan.

出版信息

Ann Rheum Dis. 2019 Oct;78(10):1305-1319. doi: 10.1136/annrheumdis-2019-215164. Epub 2019 Jul 26.

OBJECTIVE

To evaluate the efficacy and safety of the oral Janus kinase (JAK) inhibitor peficitinib versus placebo in Japanese patients with rheumatoid arthritis (RA).

METHODS

In this multicentre, double-blind, parallel-group, placebo-controlled phase III study, patients with RA and inadequate response to methotrexate (MTX) were randomised 1:1:1 to placebo, peficitinib 100 mg once daily or peficitinib 150 mg once daily with MTX for 52 weeks. Based on baseline randomisation, at week 12, non-responders receiving placebo were switched to peficitinib until the end of treatment; the remaining patients were switched to peficitinib at week 28. Primary efficacy variables were American College of Rheumatology (ACR)20 response rate at week 12/early termination (ET) and change from baseline in van der Heijde-modified total Sharp score (mTSS) at week 28/ET.

RESULTS

519 patients were randomised and treated. Significantly more (p<0.001) peficitinib (58.6%, 100 mg; 64.4%, 150 mg) than placebo (21.8%) recipients achieved ACR20 response at week 12/ET. Significantly lower (p<0.001) mean changes from baseline in mTSS at week 28/ET occurred in peficitinib (1.62, 100 mg; 1.03, 150 mg) than placebo (3.37) recipients. Peficitinib was associated with haematological and biochemical parameter changes, and increased incidence of serious infections and herpes zoster-related disease. One death from suicide occurred in a patient in the placebo group after switching to peficitinib 100 mg.

CONCLUSIONS

In Japanese patients with RA and inadequate response to MTX, peficitinib demonstrated significant superiority versus placebo in reducing RA symptoms and suppressing joint destruction. Peficitinib had an acceptable safety and tolerability profile, with no new safety signals compared with other JAK inhibitors.

TRIAL REGISTRATION NUMBER

NCT02305849.

目的

评估口服 Janus 激酶（JAK）抑制剂培非替尼对比安慰剂在日本类风湿关节炎（RA）患者中的疗效和安全性。

方法

在这项多中心、双盲、平行分组、安慰剂对照的 III 期研究中，对接受甲氨蝶呤（MTX）治疗后应答不足的 RA 患者按 1:1:1 比例随机分组，分别接受安慰剂、培非替尼 100mg 每日 1 次或培非替尼 150mg 每日 1 次联合 MTX 治疗，疗程 52 周。根据基线随机分组，在第 12 周时，安慰剂组中无应答者转换为培非替尼直至治疗结束；其余患者在第 28 周转换为培非替尼。主要疗效变量为第 12 周/早期终止（ET）时美国风湿病学会（ACR）20 应答率和第 28 周/ET 时 van der Heijde 改良总 Sharp 评分（mTSS）的基线变化。

结果

519 例患者被随机分组并接受治疗。与安慰剂组（21.8%）相比，培非替尼（100mg 组：58.6%；150mg 组：64.4%）组更多患者在第 12 周/ET 时达到 ACR20 应答（p<0.001）。与安慰剂组（3.37）相比，培非替尼组（100mg 组：1.62；150mg 组：1.03）患者第 28 周/ET 时 mTSS 的平均变化明显更低（p<0.001）。培非替尼与血液学和生化参数变化相关，并增加严重感染和带状疱疹相关疾病的发生率。在从安慰剂转换为培非替尼 100mg 治疗的患者中，1 例患者发生自杀死亡。