目的:在基线特征定义的银屑病关节炎(PsA)患者亚组中,通过2年的guselkumab在关键疾病识别领域和患者报告结局(PRO)评估严格的疾病控制模式。
方法:这项对DISCOVER-2(Clinicaltrials.govNCT03158285)的事后分析评估了生物性未治疗的PsA患者(≥5个肿胀/≥5个压痛关节,C反应蛋白[CRP]≥0.6mg/dL)每4周(Q4W)随机分配给guselkumab;第0周和第4周,然后是Q8W;或在第24周与guselkumabQ4W交叉的安慰剂。美国风湿病学会的成就提高了50/70%(ACR50/70),研究者的全球评估(IGA)0,指炎/附着点炎的分辨率,慢性疾病治疗的功能评估(FACIT)-疲劳反应(≥4点改善),HAQ-残疾指数(HAQ-DI)反应(≥0.35点改善),PsA疾病活动评分(PASDAS)低疾病活动(LDA),在第24、52和100周,在按性别和基线药物使用定义的亚组中评估了最小疾病活动(MDA),身体质量指数,PsA持续时间,肿胀/触痛关节,CRP,和牛皮癣的严重程度/程度。缺失分类应答数据的患者被认为是无应答者。
结果:442/493(90%)guselkumab随机分组的患者在第100周完成治疗。在足够大小的患者亚组中,guselkumab与安慰剂的显着多结构域功效。在患者亚组的关键PsA域和PRO中观察到持续改善的模式:65%-85%的guselkumab随机分组患者有附着点炎/指炎消退,50%-70%的皮肤完全清除,60%-80%报告了功能/疲劳的有意义的改善,达到40%-65%的PASDASLDA,在第100周时实现了35%-50%的MDA。
结论:接受guselkumab的活性PsA患者在关键PsA领域和PRO的疾病控制方面表现出持久的严格终点,无论基线特征如何。关键点•在高度活跃的银屑病关节炎(PsA)的生物初治患者中,无论基线人口统计学和疾病特征如何,guselkumab在第24周的严格疾病终点和患者报告结局(PRO)间的疗效均一致.•在guselkumab随机的PsA患者亚组中,关节疾病活动的重大改善,完全清除蒙皮,dactyitis/enthetisresolution,临床上有意义的PRO改善,和低的整体疾病活动的成就保持到第100周。•使用guselkumab观察到疾病控制的持久严格终点成就,无论基线患者或疾病特征。
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.