古塞库单抗与戈利木单抗治疗活动性银屑病关节炎且对初始肿瘤坏死因子抑制剂反应不足的患者：EVOLUTION研究方案，一项实用的3b期、开放标签、随机、对照有效性试验

Guselkumab versus golimumab in patients with active psoriatic arthritis and inadequate response to an initial tumor necrosis factor inhibitor: study protocol for EVOLUTION, a pragmatic, phase 3b, open-label, randomized, controlled effectiveness trial.

作者信息

Ogdie Alexis, Reddy Soumya M, Gillespie Sarah H, Husni M Elaine, Scher Jose U, Salomon-Escoto Karen, Kay Jonathan, Luedders Brent A, Curtis Jeffrey R, Shields Alisa J Stephens, Chakravarty Soumya D, Gong Cinty, Walsh Jessica A

机构信息

University of Pennsylvania School of Medicine, 3400 Spruce St., White Building, Rm 5023, Philadelphia, PA, 19104, USA.

New York University Grossman School of Medicine, New York, NY, USA.

出版信息

Trials. 2025 Mar 19;26(1):96. doi: 10.1186/s13063-025-08777-y.

DOI:10.1186/s13063-025-08777-y

PMID:40102973

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11921613/

Abstract

BACKGROUND

Psoriatic arthritis (PsA) is a multi-domain, inflammatory disease impacting joints, soft tissues, and skin; tumor necrosis factor inhibitors (TNFi) are typically the first biologic following inadequate response (IR) to conventional therapies. Although guidance is lacking on therapy selection after initial TNFi failure, data suggest TNFi-IR PsA patients may benefit from switching to a different mechanism of action (MOA) vs. cycling to another TNFi. Guselkumab is a fully human monoclonal antibody targeting the interleukin-23p19 subunit. Emphasizing practicality and applicability to routine clinical practice, EVOLUTION will pragmatically evaluate whether switching to guselkumab is more effective than cycling to a second TNFi (subcutaneous [SC] golimumab) in TNFi-IR PsA patients.

METHODS

The multicenter, longitudinal, prospective, observational Psoriatic Arthritis Research Consortium study guided eligibility criteria, outcome measures, and sample size estimates. Adults seen in clinical practice with active PsA (≥ 1 swollen joint) while receiving TNFi treatment will be eligible. Participants will be randomized (1:1:1) to guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at Week 0, Week 4, and Q8W; or SC golimumab 50 mg Q4W (no washout period). The novel primary composite endpoint is achievement of clinical Disease Activity in Psoriatic Arthritis (cDAPSA) low disease activity (≤ 13) and an Investigator's Global Assessment (IGA) of psoriasis score of 0/1 (scale: 0-4) at Month12. Secondary endpoints include cDAPSA + IGA 0/1 at Month 6; achievement of minimal disease activity, resolution of enthesitis and dactylitis (among patients affected at baseline) at Months 6/12; and mean changes at Months 6/12 in the 12-item PsA Impact of Disease, Dermatology Life Quality Index, Patient-Reported Outcomes Measurements Information System fatigue and depression questionnaires, and Bath Ankylosing Spondylitis Disease Activity Index (patients with physician-determined axial disease). The target sample size is 150 participants (50/treatment group); all analyses are considered exploratory.

DISCUSSION

EVOLUTION will employ a pragmatic approach, including a novel primary endpoint relevant to clinical practice, to assess whether switching to an alternate MOA biologic with guselkumab is more effective than cycling to a second TNFi among TNFi-IR PsA patients.

TRIAL REGISTRATION

This trial was registered at ClinicalTrials.gov, NCT05669833, on 3 January 2023, https://www.

CLINICALTRIALS

gov/study/NCT05669833?term=%20NCT05669833&rank=1.

摘要

背景

银屑病关节炎（PsA）是一种多领域的炎症性疾病，会影响关节、软组织和皮肤；肿瘤坏死因子抑制剂（TNFi）通常是在对传统疗法反应不足（IR）后使用的第一种生物制剂。尽管在初始TNFi治疗失败后缺乏治疗选择的指导，但数据表明，TNFi反应不足的PsA患者可能从换用不同作用机制（MOA）的药物而非换用另一种TNFi中获益。古塞库单抗是一种靶向白细胞介素-23p19亚基的全人单克隆抗体。EVOLUTION研究将强调实用性以及对常规临床实践的适用性，切实评估在TNFi反应不足的PsA患者中，换用古塞库单抗是否比换用第二种TNFi（皮下注射[SC]戈利木单抗）更有效。

方法

多中心、纵向、前瞻性观察性银屑病关节炎研究联盟的研究指导了纳入标准、结局指标和样本量估计。在接受TNFi治疗时临床诊断为活动性PsA（≥1个肿胀关节）的成年人符合纳入条件。参与者将被随机分组（1:1:1），分别接受每4周一次（Q4W）注射100mg古塞库单抗；在第0周、第4周注射100mg古塞库单抗，之后每8周一次（Q8W）；或每4周一次（Q4W）皮下注射50mg戈利木单抗（无洗脱期）。新的主要复合终点是在第12个月时达到银屑病关节炎临床疾病活动度（cDAPSA）低疾病活动度（≤13）且银屑病的研究者整体评估（IGA）评分为0/1（范围：0 - 4）。次要终点包括第6个月时的cDAPSA + IGA 0/1；在第6/12个月时达到最小疾病活动度、肌腱端炎和指（趾）炎缓解（基线时受影响的患者）；以及在第6/12个月时12项银屑病关节炎疾病影响量表、皮肤病生活质量指数、患者报告结局测量信息系统疲劳和抑郁问卷以及巴斯强直性脊柱炎疾病活动指数（有医生确定的轴向疾病的患者）的平均变化。目标样本量为150名参与者（每组50名）；所有分析均视为探索性分析。