Ogdie Alexis, Merola Joseph F, Mease Philip J, Ritchlin Christopher T, Scher Jose U, Lafferty Kimberly Parnell, Chan Daphne, Chakravarty Soumya D, Langholff Wayne, Wang Yanli, Choi Olivia, Krol Yevgeniy, Gottlieb Alice B
University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
BMC Rheumatol. 2024 May 21;8(1):20. doi: 10.1186/s41927-024-00386-7.
Tumor necrosis factor inhibitors (TNFi) are frequently chosen as the first biologic for patients with psoriatic arthritis (PsA). Given that many patients with PsA are TNFi inadequate responders (TNF-IR; either inadequate efficacy or intolerance), treatments utilizing alternative mechanisms of action are needed. In phase 3 studies, the fully human interleukin (IL)-23p19 subunit-inhibitor, guselkumab, was efficacious in patients with active PsA, including TNFi-IR. Efficacy was generally consistent between TNFi-naïve and TNFi-experienced cohorts; however, in the latter, higher response rates have been observed with the Q4W dosing regimen relative to the Q8W dosing regimen for some endpoints, suggesting the need to evaluate whether more frequent dosing may provide an incremental clinical benefit for TNFi-IR patients.
The phase 3b SOLSTICE study will assess guselkumab efficacy and safety in TNFi-IR PsA patients. Eligibility criteria include a PsA diagnosis for ≥ 6 months; active disease (≥ 3 swollen, ≥ 3 tender joints, C-reactive protein ≥ 0.3 mg/dL); and inadequate efficacy with, and/or intolerance to, one prior TNFi. Participants will be randomized 1:1:1 to guselkumab Q4W or Q8W or placebo→guselkumab Q4W (at Week 24). The primary endpoint is the proportion of patients achieving ≥ 20% improvement in the American College of Rheumatology criteria (ACR20) at Week 24. Major secondary endpoints include ACR50, ACR70; an Investigator's Global Assessment (IGA) of psoriasis score of 0/1 plus ≥ 2-grade reduction and ≥ 90% improvement in Psoriasis Area and Severity Index (both among patients with ≥ 3% body surface area affected by psoriasis and baseline IGA ≥ 2); minimal/very low disease activity; and changes from baseline in Health Assessment Questionnaire-Disability Index, the 36-item Short-Form Health Survey Physical Component Summary, and Functional Assessment of Chronic Illness Therapy-Fatigue scores. The target sample size (N = 450) is estimated to provide > 90% power in detecting differences between each guselkumab group and the placebo group for the primary endpoint assuming a 2-sided α = 0.05. Cochran-Mantel-Haenszel testing and analyses of covariance will be used to compare efficacy for binary and continuous endpoints, respectively.
Findings from the phase 3b SOLSTICE study, the design of which was informed by results from previously conducted phase 3 studies, is expected to provide important efficacy and safety information on guselkumab therapy in TNFi-IR patients with PsA.
This trial was registered at ClinicalTrials.gov, NCT04936308, on 23 June 2021.
肿瘤坏死因子抑制剂（TNFi）常被选为银屑病关节炎（PsA）患者的首选生物制剂。鉴于许多PsA患者是TNFi反应不足者（TNF-IR；即疗效不足或不耐受），需要采用具有替代作用机制的治疗方法。在3期研究中，全人源白细胞介素（IL）-23p19亚基抑制剂古塞库单抗对活动性PsA患者有效，包括TNF-IR患者。在未使用过TNFi和使用过TNFi的队列中，疗效总体一致；然而，在后者中，对于某些终点，相对于每8周一次的给药方案，每4周一次的给药方案观察到更高的缓解率，这表明需要评估更频繁给药是否可能为TNF-IR患者带来额外的临床益处。
3b期SOLSTICE研究将评估古塞库单抗在TNF-IR PsA患者中的疗效和安全性。纳入标准包括PsA诊断≥6个月；疾病活动（≥3个肿胀关节、≥3个压痛关节、C反应蛋白≥0.3mg/dL）；以及对一种先前的TNFi疗效不足和/或不耐受。参与者将按1:1:1随机分为接受每4周一次或每8周一次的古塞库单抗或安慰剂→每4周一次的古塞库单抗（在第24周）。主要终点是在第24周达到美国风湿病学会标准（ACR20）改善≥20%的患者比例。主要次要终点包括ACR50、ACR70；研究者对银屑病的整体评估（IGA）评分为0/1加≥2级改善，以及银屑病面积和严重程度指数改善≥90%（在银屑病累及体表面积≥3%且基线IGA≥2的患者中）；最小/极低疾病活动度；以及健康评估问卷-残疾指数、36项简明健康调查身体成分总结和慢性病治疗功能评估-疲劳评分相对于基线的变化。目标样本量（N = 450）估计在假设双侧α = 0.05的情况下，在检测每个古塞库单抗组与安慰剂组之间主要终点的差异时具有>9０%的检验效能。将分别使用 Cochrａn-Mａｎｔｅｌ-Hａｅｎｓｚｅｌ检验和协方差分析来比较二元和连续终点的疗效。
3b期SOLSTICE研究的结果有望提供关于古塞库单抗治疗TNF-IR PsA患者的重要疗效和安全性信息，该研究的设计参考了先前进行的3期研究的结果。
本试验于2021年6月23日在ClinicalTrials.gov注册，注册号为NCT04936308。
