古塞库单抗早期改善与银屑病关节炎的持续控制相关：两项3期试验的事后分析
Early Improvements with Guselkumab Associate with Sustained Control of Psoriatic Arthritis: Post hoc Analyses of Two Phase 3 Trials.
作者信息
Curtis Jeffrey R, Deodhar Atul, Soriano Enrique R, Rampakakis Emmanouil, Shawi May, Shiff Natalie J, Han Chenglong, Tillett William, Gladman Dafna D
机构信息
Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA.
Division of Arthritis and Rheumatic Diseases, Oregon Health and Science University, Portland, OR, USA.
出版信息
Rheumatol Ther. 2024 Dec;11(6):1501-1517. doi: 10.1007/s40744-024-00702-0. Epub 2024 Sep 11.
INTRODUCTION
Patterns of treatment response can inform clinical decision-making. This study assessed the course and impact of achieving minimal clinically important improvement (MCII) in clinical measures and patient-reported outcomes (PROs) with guselkumab in patients with active psoriatic arthritis (PsA).
METHODS
Post hoc analyses evaluated 1120 patients with PsA receiving guselkumab every 4 or 8 weeks (Q4W/Q8W) or placebo from DISCOVER-1 (31% tumor necrosis factor inhibitor-experienced) and DISCOVER-2 (biologic-naïve). Achievement of MCII in clinical Disease Activity Index for PsA (cDAPSA), patient global assessment (PtGA) of arthritis, PtGA of psoriasis, patient-reported pain, Functional Assessment of Chronic Illness Therapy-Fatigue, Health Assessment Questionnaire-Disability Index, 36-item Short-Form Health Survey Physical Component Summary score, PtGA Arthritis + Psoriasis, and PsA Disease Activity Score (PASDAS) was compared between the guselkumab and placebo groups using Cox regression. Logistic regression adjusting for baseline factors evaluated associations between early (W4/W8) MCII achievement and stringent response (≥%50/%70 improvement in American College of Rheumatology response criteria, cDAPSA low disease activity [LDA], PASDAS LDA, and minimal disease activity) at W24/W52 among guselkumab-randomized patients.
RESULTS
Among patients with highly active PsA (baseline cDAPSA = 44.1-45.0, PASDAS = 6.4-6.5), times to MCII were significantly faster for guselkumab vs. placebo (hazard ratios 1.3-2.5; P < 0.05). Across measures, at first timepoint assessed, MCII rates were significantly higher with guselkumab (Q4W/Q8W 28-68%/29-65%) vs. placebo (19-47%; both P < 0.05). Early (W4/W8) MCII with guselkumab associated with higher odds of achieving stringent responses at W24/W52 (odds ratios 1.4-17.2/1.4-5.4).
CONCLUSIONS
In a mixed PsA population, significant proportions of patients treated with guselkumab achieved early (W4/W8) MCII across clinical and PRO measures, which associated with a higher likelihood of attaining clinically relevant improvements and low levels of disease activity at W24/W52.
TRIAL REGISTRATION
DISCOVER-1 (NCT03162796). DISCOVER-2 (NCT03158285).
引言
治疗反应模式可为临床决策提供参考。本研究评估了在活动性银屑病关节炎（PsA）患者中，古塞库单抗治疗实现临床指标和患者报告结局（PRO）的最小临床重要改善（MCII）的过程及影响。
方法
事后分析评估了1120例来自DISCOVER-1（31%曾使用肿瘤坏死因子抑制剂）和DISCOVER-2（未使用过生物制剂）研究中每4周或8周接受一次古塞库单抗（Q4W/Q8W）或安慰剂治疗的PsA患者。使用Cox回归比较了古塞库单抗组和安慰剂组在银屑病关节炎临床疾病活动指数（cDAPSA）、关节炎患者整体评估（PtGA）、银屑病患者整体评估、患者报告的疼痛、慢性病治疗功能评估-疲劳、健康评估问卷-残疾指数、36项简短健康调查身体成分汇总得分、PtGA关节炎+银屑病以及PsA疾病活动评分（PASDAS）方面达到MCII的情况。对基线因素进行调整的逻辑回归评估了在随机接受古塞库单抗治疗的患者中，早期（第4/8周）达到MCII与第24/52周达到严格缓解（美国风湿病学会缓解标准改善≥50%/70%、cDAPSA低疾病活动度[LDA]、PASDAS LDA以及最小疾病活动度）之间的关联。
结果
在高活动性PsA患者（基线cDAPSA = 44.1 - 45.0，PASDAS = 6.4 - 6.5）中，与安慰剂相比，古塞库单抗达到MCII的时间显著更快（风险比1.3 - 2.5；P < 0.05）。在所有评估指标中，在首次评估时间点，古塞库单抗（Q4W/Q8W 28% - 68%/29% - 65%）达到MCII的比例显著高于安慰剂（19% - 47%；P均< 0.05）。早期（第4/8周）使用古塞库单抗达到MCII与在第24/52周达到严格缓解的较高几率相关（优势比1.4 - 17.2/1.4 - 5.4）。
结论
在混合的PsA患者群体中，接受古塞库单抗治疗的患者中有很大比例在早期（第4/8周）在临床和PRO指标方面达到MCII，这与在第24/52周获得临床相关改善和低疾病活动水平的较高可能性相关。
试验注册
DISCOVER-1（NCT03162796）。DISCOVER-2（NCT03158285）。
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