托法替尼治疗银屑病关节炎患者的疗效、安全性和持久性的性别差异：3 期试验和长期扩展的事后分析。
Sex differences in the efficacy, safety and persistence of patients with psoriatic arthritis treated with tofacitinib: a post-hoc analysis of phase 3 trials and long-term extension.
机构信息
Women's College Research Institute, University of Toronto, Toronto, Ontario, Canada.
Schroeder Arthritis Institute and Krembil Research Institute, Toronto Western Hospital, Toronto, Ontario, Canada.
出版信息
RMD Open. 2023 Mar;9(1). doi: 10.1136/rmdopen-2022-002718.
BACKGROUND
Evaluate the impact of sex on tofacitinib efficacy, safety and persistence (time to discontinuation) in patients with psoriatic arthritis (PsA).
METHODS
Data were pooled from two phase 3 randomised controlled trials. Patients were randomised to tofacitinib 5 mg or 10 mg two times per day, adalimumab 40 mg every 2 weeks or placebo. Efficacy outcomes to month 12 included American College of Rheumatology (ACR)20/50/70, minimal disease activity (MDA), Psoriasis Area Severity Index (PASI)75, change from baseline (∆) in Health Assessment Questionnaire-Disability Index (HAQ-DI) and ∆Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Safety was assessed to month 12 and persistence was assessed to month 42 of a long-term extension study.
RESULTS
Overall, 816 patients were included (54.3% females). At baseline, higher tender joint counts, enthesitis scores and worse HAQ-DI and FACIT-F were reported in females versus males; presence of dactylitis and PASI were greater in males versus females. At month 3, tofacitinib efficacy generally exceeded placebo in both sexes. Overall, similar ACR20/50/70, PASI75, ∆HAQ-DI and ∆FACIT-F were observed for tofacitinib between sexes; females were less likely to achieve MDA. Similar proportions of males/females receiving tofacitinib (both doses) experienced treatment-emergent adverse events (AEs). Serious AEs occurred in 3.4%/6.6% and 4.0%/5.9% males/females with tofacitinib 5 mg and 10 mg two times per day. Persistence was generally similar between sexes.
CONCLUSION
Tofacitinib efficacy exceeded placebo in both sexes and was comparable between sexes. Consistent with previous studies of PsA treatments, females were less likely to achieve MDA, likely due to baseline differences. Safety and time to discontinuation were generally similar between sexes.
TRIAL REGISTRATION NUMBER
NCT01877668; NCT01882439; NCT01976364.
背景
评估托法替布在银屑病关节炎（PsA）患者中的疗效、安全性和持久性（停药时间）是否存在性别差异。
方法
数据来自两项 3 期随机对照试验的汇总。患者被随机分配接受托法替布 5mg 或 10mg，每日两次，阿达木单抗 40mg，每 2 周一次或安慰剂治疗。治疗 12 个月的疗效终点包括美国风湿病学会（ACR）20/50/70 应答、微小疾病活动度（MDA）、银屑病面积和严重程度指数（PASI）75、健康评估问卷残疾指数（HAQ-DI）基线变化（∆）和慢性疾病治疗疲劳功能评估（FACIT-F）。安全性评估至长期扩展研究的 12 个月，持久性评估至 42 个月。
结果
共纳入 816 例患者（54.3%为女性）。基线时，女性的压痛关节数、附着点炎评分和 HAQ-DI、FACIT-F 较差；男性的指（趾）炎和 PASI 评分更高。治疗 3 个月时，托法替布在两性中的疗效均优于安慰剂。两性的托法替布的 ACR20/50/70、PASI75、HAQ-DI 和 FACIT-F 总体相似；女性达到 MDA 的比例较低。接受托法替布（两种剂量）治疗的男性/女性患者发生治疗相关不良事件（AE）的比例相似。托法替布 5mg 和 10mg，每日两次的治疗中，分别有 3.4%/6.6%和 4.0%/5.9%的男性/女性出现严重 AE。两性的持久性总体相似。
结论
托法替布在两性中的疗效均优于安慰剂，两性之间疗效相当。与之前 PsA 治疗的研究一致，女性达到 MDA 的比例较低，可能与基线差异有关。安全性和停药时间在两性中总体相似。
临床试验注册
NCT01877668；NCT01882439；NCT01976364。
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