Efficacy and Safety of Tofacitinib in Patients with Psoriatic Arthritis or Ankylosing Spondylitis by Cigarette Smoking Status.

IF 2.9 3区医学 Q2 RHEUMATOLOGY

Rheumatology and Therapy Pub Date : 2024-12-01 Epub Date: 2024-09-25 DOI:10.1007/s40744-024-00711-z

Alexis Ogdie, Lars E Kristensen, Enrique R Soriano, Servet Akar, Yanhui Sun, David Gruben, Lara Fallon, Cassandra D Kinch, Dafna D Gladman

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引用次数: 0

Abstract

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.

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按吸烟状况区分托法替尼对银屑病关节炎或强直性脊柱炎患者的疗效和安全性

简介：银屑病关节炎（PsA）和强直性脊柱炎（AS）的常规治疗研究表明，目前/过去吸烟者与从不吸烟者相比，对肿瘤坏死因子抑制剂的反应减弱。这项事后分析根据试验筛选时的吸烟状况评估了托法替尼对PsA或AS患者的疗效和安全性：方法：根据目前/过去与从不吸烟者的状况，对PsA试验3期和长期延长期（仅安全性）以及AS试验2期和3期的汇总数据进行评估。分析包括托法替尼5毫克（PsA/AS）和10毫克（仅PsA）每日两次（BID）或安慰剂的疗效和安全性数据，以及托法替尼2毫克和10毫克每日两次的AS安全性数据。疗效结果包括美国风湿病学会≥50%应答（ACR50）和最低疾病活动度（MDA）应答至月（M）6/M3（托法替尼/安慰剂）的PsA；以及脊柱关节炎国际协会应答评估（ASAS40）和AS疾病活动度评分（ASDAS）结果≥40%的改善：PsA/AS队列包括342/178名当前/过去吸烟者和572/194名从不吸烟者。对于M3/W6（PsA/AS），托法替尼的疗效普遍高于安慰剂，而对于M6/W16（PsA/AS），目前/过去和从不吸烟者的疗效相当。在接受≥1个托法替尼剂量的患者中，PsA患者M48的调整后治疗突发不良事件（TEAE）/严重AE（SAE）/因AE而停药的发生率（IRs）在目前/过去与从不吸烟者中更高；AS患者W48的调整后TEAE发生率（IRs）在目前/过去与从不吸烟者中更高，但SAE/因AE而停药的发生率（IRs）相似：结论：在PsA和AS患者中，托法替尼的疗效高于安慰剂，且在不同吸烟类别中疗效相当。调整后的IRs在PsA的TEAEs、SAEs、因AEs而停药方面，以及在AS的TEAEs方面，当前/既往吸烟者高于从不吸烟者，补充了有关脊柱关节炎患者吸烟与合并症之间关系的报道。研究结果支持对有吸烟史的PsA或AS患者加强监测/警惕：试验注册：ClinicalTrials.gov：NCT01877668/NCT01882439/NCT03486457/NCT01976364/NCT01786668/NCT03502616.

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来源期刊

Rheumatology and Therapy RHEUMATOLOGY-

CiteScore

6.00

自引率

5.30%

发文量

审稿时长

6 weeks

期刊介绍： Aims and Scope Rheumatology and Therapy is an international, open access, peer reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world and health outcomes research around the discovery, development, and use of rheumatologic therapies. Studies relating to diagnosis, pharmacoeconomics, public health, quality of life, and patient care, management, and education are also welcomed. Areas of focus include, but are not limited to, rheumatoid arthritis, gout, gouty arthritis, psoriatic arthritis, osteoarthritis, juvenile idiopathic/rheumatoid arthritis, systemic lupus erythematosus, axial spondyloarthritis, Pompe’s disease, inflammatory joint conditions, musculoskeletal conditions, systemic sclerosis, and fibromyalgia. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, case reports, trial protocols, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Rheumatology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research. Ethics and Disclosures The journal is a member of the Committee on Publication Ethics (COPE) and subscribes to its principles on how to deal with acts of misconduct thereby committing to investigate allegations of misconduct in order to ensure the integrity of research. Content in this journal is peer-reviewed (Single-blind). For more information on our publishing ethics policies, please see here: https://www.springer.com/gp/editorial-policies Rapid Publication The journal’s rapid publication timelines aim for a peer review decision within 2 weeks of submission. If an article is accepted it will be published online 3-4 weeks from acceptance. These rapid timelines are achieved through the combination of a dedicated in-house editorial team, who closely manage article workflow, and an extensive Editorial and Advisory Board who assist with rapid peer review. This allows the journal to support the rapid dissemination of research, whilst still providing robust peer review. Combined with the journal’s open access model this allows for the rapid and efficient communication of the latest research and reviews, allowing the advancement of rheumatologic therapies. 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For further information about digital features, please contact the journal editor (see ‘Contact the Journal’ for email address), and see the ‘Guidelines for digital features and plain language summaries’ document under ‘Submission guidelines’. For examples of digital features please visit: https://springerhealthcare.com/expertise/publishing-digital-features/ Preprints We encourage posting of preprints of primary research manuscripts on preprint servers, authors'' or institutional websites, and open communications between researchers whether on community preprint servers or preprint commenting platforms. Posting of preprints is not considered prior publication and will not jeopardize consideration in our journals. Authors should disclose details of preprint posting during the submission process or at any other point during consideration in the journal. 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