Department of Rheumatology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences, Beijing, China.
Key Laboratory of Rheumatology & Clinical Immunology, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China.
Int J Rheum Dis. 2021 Dec;24(12):1530-1539. doi: 10.1111/1756-185X.14235. Epub 2021 Nov 15.
This study assessed the efficacy and safety of upadacitinib (UPA), in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), in Chinese, Brazilian, and South Korean patients with active rheumatoid arthritis (RA) and an inadequate response (IR) to csDMARDs.
Patients on stable csDMARDs were randomized (1:1) to once-daily UPA 15 mg or matching placebo (PBO) for a 12-week, double-blind period. The primary endpoint was the proportion of patients achieving ≥20% improvement in American College of Rheumatology criteria (ACR20) at week 12.
In total, 338 patients were randomized and treated, of whom 310 (91.7%) completed the double-blind phase. The study met the primary endpoint of ACR20 at week 12 for UPA 15 mg vs PBO (71.6% vs 31.4%, P < .001), with a treatment difference observed as early as week 1. All ranked and other key secondary endpoints, including more stringent responses such as ACR50, ACR70 (≥50%/70% improvement in ACR criteria), and Disease Activity Score in 28 joints using C-reactive protein <2.6, were met for UPA 15 mg vs PBO. The incidence of serious infections (2.4% vs 0.6%) and herpes zoster (HZ: 1.8% vs 0.6%) was higher with UPA 15 mg vs PBO. There was one case of venous thromboembolism reported in the UPA group.
UPA 15 mg in combination with csDMARDs demonstrated clinical and functional improvement and an acceptable safety profile over 12 weeks among patients from China, Brazil, and South Korea who had moderately to severely active RA and an IR to csDMARDs.
本研究评估了乌帕替尼（UPA）联合常规合成疾病修饰抗风湿药物（csDMARDs）在对 csDMARDs 应答不足（IR）的中国、巴西和韩国中重度活动期类风湿关节炎（RA）患者中的疗效和安全性。
接受稳定 csDMARDs 治疗的患者按 1:1 随机分配至每日一次 UPA 15mg 或匹配安慰剂（PBO）组，进行 12 周双盲治疗。主要终点为第 12 周时达到美国风湿病学会（ACR）20%改善的患者比例（ACR20）。
共 338 例患者随机分组并接受治疗，其中 310 例（91.7%）完成双盲期治疗。研究达到了 UPA 15mg 组与 PBO 组在第 12 周时的主要终点 ACR20（71.6% vs 31.4%，P < 0.001），治疗差异早在第 1 周即观察到。UPA 15mg 组还达到了所有次要终点（包括更严格的应答，如 ACR50、ACR70（ACR 标准改善≥50%/70%）和 28 关节 C 反应蛋白<2.6 的疾病活动评分），而 PBO 组未达到。UPA 15mg 组的严重感染（2.4% vs 0.6%）和带状疱疹（HZ：1.8% vs 0.6%）发生率高于 PBO 组。UPA 组报告了 1 例静脉血栓栓塞事件。
在对 csDMARDs 应答不足的中国、巴西和韩国中重度活动期 RA 患者中，UPA 15mg 联合 csDMARDs 在 12 周时可改善临床和功能，且安全性可接受。
