Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.
Pfizer Inc, Beijing, China.
RMD Open. 2023 Jan;9(1). doi: 10.1136/rmdopen-2022-002559.
Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, were evaluated in a 6-month, double-blind, phase 3 study in Chinese patients with active (polyarthritic) psoriatic arthritis (PsA) and inadequate response to ≥1 conventional synthetic disease-modifying antirheumatic drug.
Patients were randomised (2:1) to tofacitinib 5 mg twice daily (N=136) or placebo (N=68); switched to tofacitinib 5 mg twice daily after month (M)3 (blinded).
American College of Rheumatology (ACR50) response at M3. Secondary endpoints (through M6) included: ACR20/50/70 response; change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI); ≥75% improvement in Psoriasis Area and Severity Index (PASI75) response, and enthesitis and dactylitis resolution. Safety was assessed throughout.
The primary endpoint was met (tofacitinib 5 mg twice daily, 38.2%; placebo, 5.9%; p<0.0001). M3 ACR20/ACR70/PASI75 responses, and enthesitis and dactylitis resolution rates, were higher and HAQ-DI reduction was greater for tofacitinib 5 mg twice daily versus placebo. Incidence of adverse events (AEs)/serious AEs (M0-3): 68.4%/0%, tofacitinib 5 mg twice daily; 75.0%/4.4%, placebo. One death was reported with placebo→tofacitinib 5 mg twice daily (due to accident). One serious infection, non-serious herpes zoster, and lung cancer case each were reported with tofacitinib 5 mg twice daily; four serious infections and one non-serious herpes zoster case were reported with placebo→tofacitinib 5 mg twice daily (M0-6). No non-melanoma skin cancer, major adverse cardiovascular or thromboembolism events were reported.
In Chinese patients with PsA, tofacitinib efficacy was greater than placebo (primary and secondary endpoints). Tofacitinib was well tolerated; safety outcomes were consistent with the established safety profile in PsA and other indications.
NCT03486457.
在一项为期 6 个月、双盲、3 期研究中，评估口服 Janus 激酶抑制剂托法替布在对 ≥1 种传统合成疾病修饰抗风湿药物应答不足的中国活动性（多关节炎型）银屑病关节炎（PsA）患者中的疗效和安全性。
患者按 2:1 随机分配至托法替布 5mg，每日 2 次（N=136）或安慰剂（N=68）；第 3 个月（M）时转换为托法替布 5mg，每日 2 次（盲态）。
M3 时美国风湿病学会（ACR）50 应答。次要终点（至 M6）包括：ACR20/50/70 应答；从基线变化的健康评估问卷残疾指数（HAQ-DI）；75%以上的银屑病面积和严重程度指数（PASI75）应答改善，以及附着点炎和指（趾）炎消退。整个研究过程中评估安全性。
主要终点达到（托法替布 5mg，每日 2 次，38.2%；安慰剂，5.9%；p<0.0001）。M3 时托法替布 5mg，每日 2 次的 ACR20/ACR70/PASI75 应答率、附着点炎和指（趾）炎消退率较高，且 HAQ-DI 降低更大；托法替布 5mg，每日 2 次不良事件（AE）/严重 AE（M0-3）发生率为 68.4%/0%，安慰剂为 75.0%/4.4%。安慰剂转换为托法替布 5mg，每日 2 次时报告 1 例死亡（因事故）。托法替布 5mg，每日 2 次时报告 1 例严重感染、1 例非严重带状疱疹和 1 例肺癌病例；安慰剂转换为托法替布 5mg，每日 2 次时报告 4 例严重感染和 1 例非严重带状疱疹病例（M0-6）。未报告非黑色素瘤皮肤癌、主要不良心血管或血栓栓塞事件。
在中国 PsA 患者中，托法替布的疗效优于安慰剂（主要和次要终点）。托法替布具有良好的耐受性；安全性结果与 PsA 和其他适应证的既定安全性特征一致。
NCT03486457。
