Efficacy and Safety of Deucravacitinib, a Selective, Allosteric TYK2 Inhibitor, by Baseline DMARD Use in a Phase 2 Psoriatic Arthritis Study: A Post Hoc Analysis.

IF 2.9 3区医学 Q2 RHEUMATOLOGY

Rheumatology and Therapy Pub Date : 2025-10-01 Epub Date: 2025-07-05 DOI:10.1007/s40744-025-00776-4

Atul Deodhar, Miroslawa Nowak, June Y Ye, Tom Lehman, Subhashis Banerjee, Philip J Mease

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引用次数: 0

Abstract

Introduction: This study aimed to evaluate the influence of background conventional synthetic disease-modifying antirheumatic drug (csDMARD) use on efficacy and safety of deucravacitinib, a first-in-class, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, in patients with psoriatic arthritis (PsA).

Methods: This phase 2, double-blind trial randomized 203 patients with active PsA 1:1:1 to oral placebo, deucravacitinib 6 mg, or deucravacitinib 12 mg once daily for 16 weeks. Patients had failed or were intolerant to ≥ 1 non-steroidal anti-inflammatory drug (NSAID), glucocorticoid, csDMARD and/or one tumour necrosis factor inhibitor. Patients were not stratified by csDMARD use and were allowed one background csDMARD if used for ≥ 3 months with stable dose for > 28 days prior to day 1; patients could not initiate new csDMARD treatment. This post hoc analysis evaluated the influence of background csDMARD use on efficacy outcomes, which included American College of Rheumatology (ACR) 20 responses and ACR scoring components; Psoriasis Area and Severity Index (PASI) scores; Psoriatic Arthritis Disease Activity Scores (PASDAS); and on safety measures.

Results: Baseline clinical characteristics and disease activity were generally similar among subgroups regardless of csDMARD use. At baseline, 65.0% of patients were taking background csDMARDs and among these 84.1% were taking methotrexate; percentages of methotrexate use were similar across groups. Similar ACR 20 response rates at week 16 were observed with deucravacitinib treatment in patients with vs without baseline csDMARD use compared with placebo (deucravacitinib 6 mg: 57.8% vs 44.0%; deucravacitinib 12 mg: 62.8% vs 62.5%; and placebo: 31.8% vs 31.8%, respectively). Similar responses with deucravacitinib compared with placebo, regardless of background csDMARD use, were observed in individual ACR components, PASI score, and PASDAS. The safety profile of deucravacitinib treatment was similar in patients with and without csDMARD use.

Conclusion: Background csDMARD use did not affect the efficacy or safety of deucravacitinib in this phase 2 PsA study. Graphical Abstract available for this article.

Trial registration: ClinicalTrials.gov ( https://clinicaltrials.gov ): NCT03881059.

Abstract Image

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Deucravacitinib（一种选择性变质TYK2抑制剂）在2期银屑病关节炎研究中基线使用的疗效和安全性：事后分析

简介：本研究旨在评价背景下使用常规合成疾病缓解抗风湿药（csDMARD）对deucravacitinib（一种口服、选择性、变构酪氨酸激酶2 （TYK2）抑制剂）治疗银屑病关节炎（PsA）患者疗效和安全性的影响。方法：这项2期双盲试验将203例PsA为1:1:1的患者随机分配给口服安慰剂、deucravacitinib 6mg或deucravacitinib 12mg，每天一次，持续16周。患者对≥1种非甾体抗炎药（NSAID）、糖皮质激素、csDMARD和/或一种肿瘤坏死因子抑制剂无效或不耐受。患者未按使用csDMARD进行分层，如果使用csDMARD≥3个月，则允许在第1天前28天使用稳定剂量的csDMARD；患者不能开始新的csDMARD治疗。本事后分析评估了背景使用csDMARD对疗效结果的影响，包括美国风湿病学会（ACR） 20反应和ACR评分成分；银屑病面积及严重程度指数（PASI）评分；银屑病关节炎疾病活动评分（PASDAS）；还有安全措施。结果：无论是否使用csDMARD，亚组的基线临床特征和疾病活动性基本相似。在基线时，65.0%的患者正在服用背景csDMARDs，其中84.1%的患者正在服用甲氨蝶呤；各组间甲氨蝶呤使用率相似。与安慰剂相比，基线csDMARD使用与未使用deucravacitinib治疗的患者在第16周的acr20缓解率相似(deucravacitinib 6 mg: 57.8% vs 44.0%；Deucravacitinib 12mg: 62.8% vs 62.5%；安慰剂：分别为31.8%和31.8%)。与安慰剂相比，无论背景是否使用csDMARD，在单个ACR成分、PASI评分和PASDAS中观察到deucravacitinib的相似反应。在使用和未使用csDMARD的患者中，deucravacitinib治疗的安全性相似。在这项2期PsA研究中，csDMARD的使用并未影响deucravacitinib的疗效和安全性。本文提供的图形摘要。试验注册：ClinicalTrials.gov (https://clinicaltrials.gov): NCT03881059。

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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. 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