托法替布在银屑病关节炎或强直性脊柱炎患者中按吸烟状况划分的疗效与安全性
Efficacy and Safety of Tofacitinib in Patients with Psoriatic Arthritis or Ankylosing Spondylitis by Cigarette Smoking Status.
作者信息
Ogdie Alexis, Kristensen Lars E, Soriano Enrique R, Akar Servet, Sun Yanhui, Gruben David, Fallon Lara, Kinch Cassandra D, Gladman Dafna D
机构信息
Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
The Parker Institute, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark.
出版信息
Rheumatol Ther. 2024 Dec;11(6):1649-1664. doi: 10.1007/s40744-024-00711-z. Epub 2024 Sep 25.
INTRODUCTION
Routine care studies of psoriatic arthritis (PsA) and ankylosing spondylitis (AS) demonstrated attenuated responses to tumor necrosis factor inhibitors in current/past versus never smokers. This post hoc analysis assessed tofacitinib efficacy and safety in patients with PsA or AS by cigarette smoking status at trial screening.
METHODS
Pooled data from phase 3 and long-term extension (safety only) PsA trials and phase 2 and 3 AS trials were assessed by current/past versus never smoker status. Analysis included efficacy and safety data for tofacitinib 5 (PsA/AS) and 10 (PsA only) mg twice daily (BID) or placebo, and safety data in AS for tofacitinib 2 and 10 mg BID. Efficacy outcomes included American College of Rheumatology ≥ 50% responses (ACR50) and minimal disease activity (MDA) responses to month (M)6/M3 (tofacitinib/placebo) in PsA; and ≥ 40% improvement in Assessment of SpondyloArthritis international Society responses (ASAS40) and AS Disease Activity Score (ASDAS) < 2.1 responses to week (W)16 in AS. Safety was assessed to M48/W48 (PsA/AS), adjusted for treatment/smoking status/median body mass index (BMI) status/sex/trial/treatment-smoking status interaction.
RESULTS
PsA/AS cohorts included 342/178 current/past and 572/194 never smokers. Tofacitinib efficacy was generally greater versus placebo to M3/W6 (PsA/AS), and comparable in current/past and never smokers to M6/W16 (PsA/AS). In patients receiving ≥ 1 tofacitinib dose, adjusted treatment-emergent adverse event (TEAE)/serious AE (SAE)/discontinuation due to AE incidence rates (IRs) to M48 in PsA were higher in current/past versus never smokers; adjusted IRs to W48 in AS were higher in current/past versus never smokers for TEAEs, but similar for SAEs/discontinuation due to AEs.
CONCLUSIONS
In both patients with PsA and AS, tofacitinib efficacy was greater versus placebo, and comparable across smoking categories. Adjusted IRs were higher in current/past versus never smokers for TEAEs, SAEs, discontinuation due to AEs in PsA, and for TEAEs in AS, complementing reports of associations between smoking and comorbidities in spondyloarthritis. Findings support increased surveillance/caution for patients with PsA or AS with smoking history.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT01877668/NCT01882439/NCT03486457/NCT01976364/NCT01786668/NCT03502616.
引言
银屑病关节炎（PsA）和强直性脊柱炎（AS）的常规护理研究表明，与从不吸烟者相比，目前/过去吸烟者对肿瘤坏死因子抑制剂的反应减弱。这项事后分析通过试验筛查时的吸烟状况评估了托法替布在PsA或AS患者中的疗效和安全性。
方法
汇总3期和长期扩展（仅安全性）PsA试验以及2期和3期AS试验的数据，根据目前/过去吸烟者与从不吸烟者的状况进行评估。分析包括托法替布5（PsA/AS）和10（仅PsA）mg每日两次（BID）或安慰剂的疗效和安全性数据，以及托法替布2和10 mg BID在AS中的安全性数据。疗效指标包括美国风湿病学会≥50%反应（ACR50）以及PsA中至第6/3个月（托法替布/安慰剂）的最小疾病活动度（MDA）反应；以及国际脊柱关节炎协会评估反应（ASAS40）改善≥40%和AS疾病活动评分（ASDAS）<2.1至第16周（W16）在AS中的反应。安全性评估至第48个月/第48周（PsA/AS），针对治疗/吸烟状况/中位体重指数（BMI）状况/性别/试验/治疗-吸烟状况相互作用进行调整。
结果
PsA/AS队列包括342/178名目前/过去吸烟者和572/194名从不吸烟者。至第3个月/第6周（PsA/AS），托法替布的疗效总体上优于安慰剂，并且在目前/过去吸烟者和从不吸烟者中至第6个月/第16周（PsA/AS）相当。在接受≥1剂托法替布的患者中，PsA中至第48个月调整后的治疗中出现的不良事件（TEAE）/严重不良事件（SAE）/因不良事件导致的停药发生率（IRs）在目前/过去吸烟者中高于从不吸烟者；在AS中，至第48周，TEAE的调整后IRs在目前/过去吸烟者中高于从不吸烟者，但SAE/因不良事件导致的停药情况相似。
结论
在PsA和AS患者中，托法替布的疗效均优于安慰剂，且在不同吸烟类别中相当。在PsA中，目前/过去吸烟者的TEAE、SAE、因不良事件导致的停药调整后IRs高于从不吸烟者，在AS中TEAE也是如此，这补充了脊柱关节炎中吸烟与合并症之间关联的报告。研究结果支持对有吸烟史的PsA或AS患者加强监测/谨慎对待。
试验注册
ClinicalTrials.gov：NCT01877668/NCT01882439/NCT03486457/NCT01976364/NCT01786668/NCT03502616。
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