Peking University People's Hospital, Beijing, China.
Jiangxi Pingxiang People's Hospital, Pingxiang, China.
Clin Exp Rheumatol. 2020 Jul-Aug;38(4):732-741. Epub 2020 May 20.
This study evaluated the efficacy and safety of baricitinib, an oral Janus kinase (JAK)1/JAK2 inhibitor, in patients with moderately to severely active rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX) therapy.
In this phase 3, double-blind, 52-week, placebo-controlled study, 290 patients with moderately to severely active RA and inadequate response to MTX were randomly assigned 1:1 to placebo or baricitinib 4-mg once daily, stratified by country (China, Brazil, Argentina) and presence of joint erosions. Primary endpoint measures included American College of Rheumatology 20% response (ACR20) at week 12. Secondary endpoints included changes in Health Assessment Questionnaire-Disability Index (HAQ-DI) and Disease Activity Score for 28-joint counts (DAS28)-high-sensitivity C-reactive protein (hsCRP), Simplified Disease Activity Index (SDAI) score ≤3.3, mean duration of morning joint stiffness, severity of morning joint stiffness numeric rating scale (NRS 0-10), worst tiredness NRS, and worst joint pain NRS at week 12.
Most patients (approximately 80%) were from China. More patients achieved ACR20 response at week 12 with baricitinib than with placebo (58.6% vs. 28.3%; p<0.001). Statistically significant improvements were also seen in HAQ-DI, DAS28-hsCRP, morning joint stiffness, worst tiredness, and worst joint pain in the baricitinib group compared to placebo at week 12. Through week 24, rates of treatment-emergent adverse events, including infections, were higher for baricitinib compared to placebo, while serious adverse event rates were similar between baricitinib and placebo.
In patients with RA who had an inadequate response to MTX, baricitinib was associated with significant clinical improvements as compared with placebo.
本研究评估了巴瑞替尼（一种口服 Janus 激酶[JAK]1/JAK2 抑制剂）在对甲氨蝶呤（MTX）治疗反应不足的中度至重度活跃类风湿关节炎（RA）患者中的疗效和安全性。
在这项 3 期、双盲、52 周、安慰剂对照研究中，290 名对 MTX 治疗反应不足的中度至重度活跃 RA 患者按 1:1 随机分配至安慰剂或巴瑞替尼 4mg 每日一次，按国家（中国、巴西、阿根廷）和是否存在关节侵蚀进行分层。主要终点评估指标包括第 12 周时美国风湿病学会 20%反应（ACR20）。次要终点包括健康评估问卷残疾指数（HAQ-DI）和 28 个关节计数疾病活动评分（DAS28）-高敏 C 反应蛋白（hsCRP）的变化、简化疾病活动指数（SDAI）评分≤3.3、平均晨僵持续时间、晨僵严重程度数字评定量表（NRS 0-10）、最差疲劳 NRS 和最差关节疼痛 NRS。
大多数患者（约 80%）来自中国。与安慰剂相比，巴瑞替尼组在第 12 周时达到 ACR20 反应的患者比例更高（58.6% vs. 28.3%；p<0.001）。与安慰剂相比，巴瑞替尼组在第 12 周时，HAQ-DI、DAS28-hsCRP、晨僵、最差疲劳和最差关节疼痛也有显著改善。在第 24 周时，巴瑞替尼组的治疗中出现的不良反应发生率（包括感染）高于安慰剂组，而巴瑞替尼组和安慰剂组的严重不良事件发生率相似。
在对 MTX 治疗反应不足的 RA 患者中，与安慰剂相比，巴瑞替尼治疗与显著的临床改善相关。
