Gossec Laure, Baraliakos Xenofon, Aletaha Daniel, Sharaf Mohamed, Rampakakis Emmanouil, Lavie Frédéric, López-Medina Clementina, Selmi Carlo, Coates Laura C
INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Universite, Paris, France.
APHP, Rheumatology Department, Pitie Salpetriere Hospital, Paris, France.
Rheumatology (Oxford). 2025 May 1;64(5):2565-2574. doi: 10.1093/rheumatology/keae586.
Evaluate guselkumab efficacy, an anti-interleukin-23p19-subunit antibody, in patients with active psoriatic arthritis (PsA) and inadequate response to 1 or 2 tumour necrosis factor inhibitors (TNFi-IR), utilizing composite indices assessing disease activity across disease domains.
In the Phase IIIb COSMOS trial, 285 adults with TNFi-IR PsA were randomized (2:1) to receive guselkumab 100 mg or placebo at Week (W)0, W4, then every 8 weeks through W44. Patients receiving placebo crossed over to guselkumab at W24. In this post hoc analysis, composite indices evaluated included the Disease Activity Index for Psoriatic Arthritis (DAPSA), Disease Activity Score 28 (DAS28), Psoriatic Arthritis Response Criteria (PsARC), Psoriatic Arthritis Disease Activity Score (PASDAS), GRAPPA Composite score (GRACE), modified Composite Psoriatic Disease Activity Index (mCPDAI), minimal disease activity (MDA), and very low disease activity (VLDA). Through W24, treatment failure rules were applied. Through W48, non-responder imputation was used for missing data.
Greater proportions of guselkumab- than placebo-randomized patients achieved composite index endpoints relating to low disease activity (LDA; 14.8-52.4% vs 3.1-28.1%) or remission (3.7-5.3% vs 0.0-2.1%) at W24. Among guselkumab-randomized patients, LDA rates increased to W48 (DAPSA, 44.4%; DAS28, 47.8%; PASDAS, 34.4%; GRACE, 33.3%; mCPDAI, 40.2%), and 27.0% and 64.0% achieved MDA and a PsARC response, respectively. In the placebo→guselkumab crossover group, W48 response rates were similar to the guselkumab-randomized group.
Guselkumab treatment provided substantial benefits across multiple disease domains, with increasing proportions of patients achieving LDA/remission over 1 year, highlighting the effectiveness of guselkumab despite previous inadequate response to TNFi.
利用评估疾病各领域活动度的综合指标，评估抗白细胞介素-23p19亚基抗体古塞库单抗对活动性银屑病关节炎（PsA）患者且对1种或2种肿瘤坏死因子抑制剂反应不足（TNFi-IR）的疗效。
在IIIb期COSMOS试验中，285例TNFi-IR PsA成人患者被随机分组（2:1），在第0周、第4周接受古塞库单抗100mg或安慰剂治疗，然后每8周一次直至第44周。接受安慰剂的患者在第24周交叉接受古塞库单抗治疗。在这项事后分析中，评估的综合指标包括银屑病关节炎疾病活动指数（DAPSA）、疾病活动评分28（DAS28）、银屑病关节炎反应标准（PsARC）、银屑病关节炎疾病活动评分（PASDAS）、GRAPPA综合评分（GRACE）、改良综合银屑病疾病活动指数（mCPDAI）、最小疾病活动度（MDA）和极低疾病活动度（VLDA）。至第24周，应用治疗失败规则。至第48周，对缺失数据采用无反应者插补法。
在第24周时，与安慰剂组相比，更多接受古塞库单抗治疗的患者达到了与低疾病活动度（LDA；14.8 - 52.4%对3.1 - 28.1%）或缓解（3.7 - 5.3%对0.0 - 2.
