Gladman Dafna D, Nash Peter, Mease Philip J, FitzGerald Oliver, Duench Stephanie, Cadatal Mary Jane, Masri Karim R
Department of Medicine, University of Toronto, and Schroeder Arthritis Institute, Krembil Research Institute, Toronto Western Hospital, 399 Bathurst St. 1E-411, Toronto, ON, M5T 2S8, Canada.
School of Medicine, Griffith University, Brisbane, QLD, Australia.
Arthritis Res Ther. 2024 Dec 19;26(1):218. doi: 10.1186/s13075-024-03442-2.
Data on treatment switching directly from tumor necrosis factor inhibitors to tofacitinib in psoriatic arthritis (PsA) are limited. This post hoc analysis assessed efficacy and safety outcomes in patients with PsA who directly switched to tofacitinib in a long-term extension (LTE) study after receiving adalimumab (ADA) in a Phase 3 study, compared with those who continued to receive tofacitinib.
Patients with active PsA received tofacitinib 5 mg twice daily (BID) or ADA 40 mg once every 2 weeks in a 12-month, randomized, double-blind study (OPAL Broaden) and then continued or switched to tofacitinib 5 mg BID and maintained this dose in an open-label LTE study (OPAL Balance). Efficacy was assessed 3 months before the last visit and at the last visit in the Phase 3 study, and at month 3 (or month 6 for select outcomes) in the LTE study and included rates of ≥ 20/50/70% improvement in American College of Rheumatology response criteria, Psoriasis Area and Severity Index ≥ 75% improvement, Health Assessment Questionnaire-Disability Index (HAQ-DI) response (decrease from baseline ≥ 0.35 for patients with baseline HAQ-DI ≥ 0.35), Psoriatic Arthritis Disease Activity Score ≤ 3.2, and minimal disease activity; and change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue score. Safety was assessed at months 3 and 12 in both studies via incidence rates (patients with first events/100 patient-years).
Overall, 180 patients were included (ADA→tofacitinib 5 mg BID: n = 91; continuing tofacitinib 5 mg BID: n = 89). At Phase 3 baseline, patients in the ADA→tofacitinib 5 mg BID group tended to be younger and have less active disease compared with those continuing tofacitinib. Efficacy was similar between groups in the Phase 3 study, and was maintained to month 3 or 6 in the LTE study. Treatment-emergent adverse events (AEs), serious AEs, and serious infections were generally similar in the Phase 3 and LTE studies, and between groups within each study.
Tofacitinib efficacy and safety were similar in patients with PsA who directly switched from ADA to tofacitinib and those who continued tofacitinib, suggesting that patients can be directly switched from ADA to tofacitinib without any washout period.
NCT01877668; NCT01976364.
关于银屑病关节炎（PsA）患者直接从肿瘤坏死因子抑制剂转换为托法替布治疗的数据有限。这项事后分析评估了在一项3期研究中接受阿达木单抗（ADA）治疗后，在长期扩展（LTE）研究中直接转换为托法替布的PsA患者的疗效和安全性结果，并与继续接受托法替布治疗的患者进行比较。
在一项为期12个月的随机双盲研究（OPAL Broaden）中，活动性PsA患者接受每日两次5mg托法替布（BID）或每2周一次40mg ADA治疗，然后在一项开放标签的LTE研究（OPAL Balance）中继续或转换为每日两次5mg托法替布，并维持该剂量。在3期研究的最后一次访视前3个月和最后一次访视时，以及在LTE研究的第3个月（或部分结局为第6个月）评估疗效，包括美国风湿病学会反应标准改善≥20%/50%/70%的比例、银屑病面积和严重程度指数改善≥75%、健康评估问卷残疾指数（HAQ-DI）反应（基线HAQ-DI≥0.35的患者自基线下降≥0.35）、银屑病关节炎疾病活动评分≤3.2以及最小疾病活动度；以及慢性病治疗功能评估-疲劳评分相对于基线的变化。在两项研究的第3个月和第12个月通过发生率（首次发生事件的患者数/100患者年）评估安全性。
总共纳入了180例患者（ADA→每日两次5mg托法替布：n = 91；继续每日两次5mg托法替布：n = 89）。在3期基线时，ADA→每日两次5mg托法替布组的患者与继续使用托法替布的患者相比，往往更年轻且疾病活动度更低。3期研究中两组的疗效相似，并且在LTE研究中维持至第3个月或第6个月。3期和LTE研究中以及每项研究中的组间治疗中出现的不良事件（AE）、严重AE和严重感染总体相似。
直接从ADA转换为托法替布的PsA患者与继续使用托法替布的患者相比，托法替布的疗效和安全性相似，这表明患者可以直接从ADA转换为托法替布，无需任何洗脱期。
NCT01877668；NCT01976364。
