Guselkumab Efficacy in Biologic-Naïve Participants with Psoriatic Arthritis and Severe Disease Activity: Post Hoc Analysis of a Phase 3 Study.

IF 2.9 3区医学 Q2 RHEUMATOLOGY

Rheumatology and Therapy Pub Date : 2025-10-01 Epub Date: 2025-07-21 DOI:10.1007/s40744-025-00777-3

Christopher T Ritchlin, Ennio Lubrano, Maria Sole Chimenti, Evan Leibowitz, Mohamed Sharaf, Emmanouil Rampakakis, Francois Nantel, Frederic Lavie, Atul Deodhar

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引用次数: 0

Abstract

Introduction: The aim of this study was to evaluate guselkumab efficacy through week 100 in participants with psoriatic arthritis (PsA) and severe disease activity or patient global assessment (PtGA).

Methods: This post hoc analysis utilized DISCOVER-2 (NCT03158285) data from 739 biologic-naïve adults with active PsA (≥ 5 swollen/tender joints, C-reactive protein ≥ 0.6 mg/dL) randomized to guselkumab every 4 weeks (Q4W) or at weeks 0 and 4, then every 8 weeks (Q8W); or placebo with crossover to guselkumab Q4W at week 24. Severe disease activity was defined as clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) > 27, Psoriatic Arthritis Disease Activity Score (PASDAS) ≥ 5.4, and PtGA Arthritis + Psoriasis ≥ 80 mm. Least squares mean (LSM) changes in cDAPSA, PASDAS, and PtGA were estimated with mixed models for repeated measures adjusted for baseline factors.

Results: Baseline characteristics among 648 (88%), 639 (86%), and 218 (29%) participants meeting the cDAPSA, PASDAS, and PtGA criteria for severe disease activity, respectively, were generally balanced across cohorts. LSM improvements from baseline with guselkumab Q4W/Q8W vs. placebo were -5.9 (p = 0.3905)/-7.2 (p = 0.0379) for cDAPSA at week 2; -1.5/-1.5 for PASDAS (both p < 0.0001); and -30.0/-32.1 for PtGA at week 8 (both p < 0.01). Differences vs. placebo increased through week 24 in the respective cohorts with guselkumab Q4W/Q8W: -9.8/-9.0, -1.1/-1.1, -24.0/-20.2 (all p < 0.0001). Through week 100 of guselkumab Q4W/Q8W treatment, LSM improvements of 69/74%, 52/54%, and 64/63% from baseline in cDAPSA (-35.9/-35.6), PASDAS (-3.6/-3.7), and PtGA (-56.8, -55.5), respectively, were observed. Regardless of severe disease activity definition, approximately 80% of guselkumab-randomized participants who achieved low disease activity at week 24 maintained this response at week 100.

Conclusion: In biologic-naïve participants with PsA and severe disease activity, guselkumab demonstrated early and durable clinically meaningful improvements in key PsA domains through 2 years.

Trial registration: ClinicalTrials.gov, NCT03158285.

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Guselkumab对Biologic-Naïve银屑病关节炎和严重疾病活动性患者的疗效：一项3期研究的事后分析

本研究的目的是评估guselkumab在患有银屑病关节炎（PsA）和严重疾病活动性或患者整体评估（PtGA）的参与者中100周的疗效。方法：这项事后分析利用discovery -2 （NCT03158285）数据，这些数据来自739名biologic-naïve成年人，他们的PsA活性（≥5个肿胀/柔软关节，c反应蛋白≥0.6 mg/dL），随机分配到每4周（Q4W）或第0周和第4周，然后每8周（Q8W）；或安慰剂，在第24周交叉到guselkumab Q4W。严重疾病活动性定义为：银屑病关节炎临床疾病活动性指数（cDAPSA） bb0.27，银屑病关节炎疾病活动性评分(PASDAS)≥5.4，PtGA关节炎+银屑病≥80 mm。最小二乘均值（LSM）变化的cDAPSA， PASDAS，和PtGA估计混合模型的重复测量调整基线因素。结果：648名（88%）、639名（86%）和218名（29%）参与者分别符合cDAPSA、PASDAS和PtGA严重疾病活动性标准的基线特征在队列中基本平衡。第2周时，与安慰剂相比，休赛库单抗Q4W/Q8W对cDAPSA的LSM改善为-5.9 (p = 0.3905)/-7.2 (p = 0.0379)；PASDAS为-1.5/-1.5 (p < 0.0001)；结论：在患有PsA和严重疾病活动性的biologic-naïve参与者中，guselkumab在2年内显示出关键PsA结构域的早期和持久的临床有意义的改善。试验注册：ClinicalTrials.gov, NCT03158285。

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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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