Ritchlin Christopher T, Mease Philip J, Boehncke Wolf-Henning, Tesser John, Chakravarty Soumya D, Rampakakis Emmanouil, Shawi May, Schiopu Elena, Merola Joseph F, McInnes Iain B, Deodhar Atul
University of Rochester Medical Center, Rochester, NY, USA.
Rheumatology Research, Providence Swedish Medical Center, Seattle, WA, USA.
Clin Rheumatol. 2024 Aug;43(8):2551-2563. doi: 10.1007/s10067-024-06991-8. Epub 2024 Jun 7.
Evaluate patterns of stringent disease control with 2 years of guselkumab across key disease-identified domains and patient-reported outcomes (PROs) in subgroups of patients with psoriatic arthritis (PsA) defined by baseline characteristics.
This post hoc analysis of DISCOVER-2 (Clinicaltrials.gov NCT03158285) evaluated biologic-naïve PsA patients (≥ 5 swollen/ ≥ 5 tender joints, C-reactive protein [CRP] ≥ 0.6 mg/dL) randomized to guselkumab every 4 weeks (Q4W); guselkumab at Weeks 0 and 4, then Q8W; or placebo with crossover to guselkumab Q4W at Week 24. Achievement of American College of Rheumatology 50/70% improvement (ACR50/70), Investigator's Global Assessment (IGA) 0, dactylitis/enthesitis resolution, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue response (≥ 4-point improvement), HAQ-Disability Index (HAQ-DI) response (≥ 0.35-point improvement), PsA Disease Activity Score (PASDAS) low disease activity (LDA), and minimal disease activity (MDA) was assessed at Weeks 24, 52, and 100 in subgroups defined by sex and baseline medication use, body mass index, PsA duration, swollen/tender joints, CRP, and psoriasis severity/extent. Patients with missing categorical response data were considered nonresponders.
442/493 (90%) guselkumab-randomized patients completed treatment through Week 100. Significant multi-domain efficacy of guselkumab versus placebo was shown across adequately sized patient subgroups. A pattern of continuous improvement was observed across key PsA domains and PROs within patient subgroups: 65%-85% of guselkumab-randomized patients had enthesitis/dactylitis resolution, 50%-70% achieved complete skin clearance, 60%-80% reported meaningful improvements in function/fatigue, 40%-65% achieved PASDAS LDA, and 35%-50% achieved MDA at Week 100.
Patients with active PsA receiving guselkumab demonstrated durable achievement of stringent endpoints associated with disease control across key PsA domains and PROs, regardless of baseline characteristics. Key Points • Among biologic-naïve patients with highly active psoriatic arthritis (PsA), efficacy of guselkumab across stringent disease endpoints and patient-reported outcomes (PROs) at Week 24 was consistent regardless of baseline demographics and disease characteristics. • Within guselkumab-randomized PsA patient subgroups, major improvements in joint disease activity, complete skin clearance, dactylitis/enthesitis resolution, clinically meaningful improvements in PROs, and achievement of low overall disease activity were maintained through Week 100. • Durable stringent endpoint achievement indicating disease control was observed with guselkumab, regardless of baseline patient or disease characteristics.
在根据基线特征定义的银屑病关节炎（PsA）患者亚组中，评估使用古塞库单抗治疗2年期间在关键疾病领域和患者报告结局（PROs）方面的严格疾病控制模式。
对DISCOVER-2（Clinicaltrials.gov NCT03158285）进行的这项事后分析评估了初治生物制剂的PsA患者（≥5个肿胀关节/≥5个压痛关节，C反应蛋白[CRP]≥0.6mg/dL），这些患者被随机分为每4周接受一次古塞库单抗治疗（Q4W）；在第0周和第4周接受古塞库单抗治疗，然后每8周一次（Q8W）；或接受安慰剂治疗，并在第24周交叉接受Q4W的古塞库单抗治疗。在第24周、52周和100周时，对按性别、基线用药情况、体重指数、PsA病程、肿胀/压痛关节、CRP以及银屑病严重程度/范围定义的亚组患者评估美国风湿病学会改善50/70%（ACR50/70）、研究者整体评估（IGA）为0、指（趾）炎/附着点炎缓解、慢性病治疗功能评估（FACIT）-疲劳反应（改善≥4分）、健康评估问卷残疾指数（HAQ-DI）反应（改善≥0.35分）、PsA疾病活动评分（PASDAS）达到低疾病活动度（LDA）以及达到最小疾病活动度（MDA）的情况。缺失分类反应数据的患者被视为无反应者。
442/493（90%）接受古塞库单抗随机分组的患者完成了至第100周的治疗。在规模足够大的患者亚组中，显示出古塞库单抗相对于安慰剂具有显著的多领域疗效。在患者亚组的关键PsA领域和PROs中观察到持续改善的模式：在接受古塞库单抗随机分组的患者中，65%-85%的患者指（趾）炎/附着点炎得到缓解，50%-70%的患者皮肤完全清除，60%-80%的患者报告功能/疲劳有有意义的改善，40%-65%的患者达到PASDAS LDA，35%-50%的患者在第100周达到MDA。
接受古塞库单抗治疗的活动性PsA患者在关键PsA领域和PROs方面持久地达到了与疾病控制相关的严格终点，无论基线特征如何。要点• 在初治生物制剂的高度活动性银屑病关节炎（PsA）患者中，无论基线人口统计学和疾病特征如何，古塞库单抗在第24周时在严格疾病终点和患者报告结局（PROs）方面的疗效是一致的。• 在接受古塞库单抗随机分组的PsA患者亚组中，关节疾病活动度的主要改善、皮肤完全清除、指（趾）炎/附着点炎缓解、PROs的临床有意义改善以及总体低疾病活动度的达成在第100周时得以维持。• 观察到使用古塞库单抗能持久地达到表明疾病得到控制的严格终点，无论患者基线或疾病特征如何。
