Dafna D. Gladman, Peter Nash, Philip J. Mease, Oliver FitzGerald, Stephanie Duench, Mary Jane Cadatal, Karim R. Masri
{"title":"在一项开放标签的长期扩展研究中,在一项3期随机对照研究中接受阿达木单抗或托法替尼治疗的银屑病关节炎患者的疗效和安全性:事后分析","authors":"Dafna D. Gladman, Peter Nash, Philip J. Mease, Oliver FitzGerald, Stephanie Duench, Mary Jane Cadatal, Karim R. Masri","doi":"10.1186/s13075-024-03442-2","DOIUrl":null,"url":null,"abstract":"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. 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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). 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引用次数: 0
摘要
银屑病关节炎(PsA)直接从肿瘤坏死因子抑制剂转为托法替尼治疗的数据有限。这项事后分析评估了PsA患者在接受阿达木单抗(ADA)后,与继续接受托法替尼的患者相比,在长期延长(LTE)研究中直接切换到托法替尼的疗效和安全性结果。在一项为期12个月的随机双盲研究(OPAL拓宽)中,活动性PsA患者接受托法替尼5 mg每日2次(BID)或ADA 40 mg每2周1次(每2周1次),然后在一项开放标签LTE研究(OPAL Balance)中继续或切换到托法替尼5 mg BID,并维持该剂量。在3期研究的最后一次访问前3个月和最后一次访问时以及LTE研究的第3个月(或选择结果的第6个月)评估疗效,包括美国风湿病学会反应标准≥20/50/70%的改善率,银屑病面积和严重程度指数≥75%的改善率,健康评估问卷-残疾指数(HAQ-DI)反应(基线HAQ-DI≥0.35的患者从基线≥0.35下降)。银屑病关节炎疾病活动性评分≤3.2,且疾病活动性最小;慢性疾病治疗功能评估-疲劳评分与基线的变化。两项研究在第3个月和第12个月通过发病率(首次事件患者/100患者-年)评估安全性。总共纳入180例患者(ADA→tofacitinib 5 mg BID: n = 91;继续服用法替尼5mg BID: n = 89)。在3期基线时,与继续使用托法替尼的患者相比,ADA→托法替尼5mg BID组患者更年轻,活动性疾病更少。在3期研究中,两组之间的疗效相似,在LTE研究中维持到第3个月或第6个月。在3期和LTE研究中,以及每个研究的组之间,治疗出现的不良事件(ae)、严重ae和严重感染通常相似。在PsA患者中,直接从ADA切换到托法替尼和继续使用托法替尼的患者,托法替尼的疗效和安全性相似,提示患者可以直接从ADA切换到托法替尼,无需任何洗脱期。NCT01877668;NCT01976364
Efficacy and safety of tofacitinib in an open-label, long-term extension study in patients with psoriatic arthritis who received adalimumab or tofacitinib in a Phase 3 randomized controlled study: a post hoc analysis
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
期刊介绍:
Established in 1999, Arthritis Research and Therapy is an international, open access, peer-reviewed journal, publishing original articles in the area of musculoskeletal research and therapy as well as, reviews, commentaries and reports. A major focus of the journal is on the immunologic processes leading to inflammation, damage and repair as they relate to autoimmune rheumatic and musculoskeletal conditions, and which inform the translation of this knowledge into advances in clinical care. Original basic, translational and clinical research is considered for publication along with results of early and late phase therapeutic trials, especially as they pertain to the underpinning science that informs clinical observations in interventional studies.