古塞库单抗在初治的银屑病关节炎及严重疾病活动患者中的疗效：一项3期研究的事后分析
Guselkumab Efficacy in Biologic-Naïve Participants with Psoriatic Arthritis and Severe Disease Activity: Post Hoc Analysis of a Phase 3 Study.
作者信息
Ritchlin Christopher T, Lubrano Ennio, Chimenti Maria Sole, Leibowitz Evan, Sharaf Mohamed, Rampakakis Emmanouil, Nantel Francois, Lavie Frederic, Deodhar Atul
机构信息
Department of Medicine, Allergy/Immunology and Rheumatology, University of Rochester Medical Center, 400 Red Creek Dr, Ste 240, Rochester, NY, 14623, USA.
Vincenzo Tiberio Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy.
出版信息
Rheumatol Ther. 2025 Jul 21. doi: 10.1007/s40744-025-00777-3.
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.
简介
本研究旨在评估古塞库单抗在患有银屑病关节炎（PsA）且疾病活动严重或患者整体评估（PtGA）的参与者中至第100周的疗效。
方法
这项事后分析利用了DISCOVER-2（NCT03158285）的数据，该数据来自739名初治生物制剂的活动性PsA成年患者（≥5个肿胀/压痛关节，C反应蛋白≥0.6mg/dL），这些患者被随机分为每4周（Q4W）或在第0周和第4周接受古塞库单抗治疗，然后每8周（Q8W）一次；或接受安慰剂治疗，并在第24周交叉接受古塞库单抗Q4W治疗。严重疾病活动定义为银屑病关节炎临床疾病活动指数（cDAPSA）>27、银屑病关节炎疾病活动评分（PASDAS）≥5.4以及PtGA关节炎+银屑病≥80mm。使用针对基线因素进行调整的重复测量混合模型估计cDAPSA、PASDAS和PtGA的最小二乘均值（LSM）变化。
结果
分别符合cDAPSA、PASDAS和PtGA严重疾病活动标准的648名（88%）、639名（86%）和218名（29%）参与者的基线特征在各队列中总体均衡。在第2周时，与安慰剂相比，古塞库单抗Q4W/Q8W组的cDAPSA的LSM改善分别为-5.9（p=0.3905）/-7.2（p=0.0379）；PASDAS为-1.5/-1.5（均p<0.0001）；在第8周时，PtGA为-30.0/-32.1（均p<0.01）。在接受古塞库单抗Q4W/Q8W治疗的各队列中，与安慰剂相比的差异在第24周时增加：-9.8/-9.0、-1.1/-1.1、-24.0/-20.2（均p<0.0001）。在古塞库单抗Q4W/Q8W治疗至第100周时，观察到cDAPSA（-35.9/-35.6）、PASDAS（-3.6/-3.7）和PtGA（-56.8，-55.5）相对于基线的LSM改善分别为69/74%、52/54%和64/63%。无论严重疾病活动如何定义，在第24周达到低疾病活动的接受古塞库单抗随机分组的参与者中，约80%在第100周维持了这种反应。
结论
在初治生物制剂的PsA且疾病活动严重的参与者中，古塞库单抗在2年时间里在关键的PsA领域显示出早期且持久的具有临床意义的改善。
试验注册
ClinicalTrials.gov，NCT03158285。
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