Anders Hans-Joachim, Chan Tak Mao, Sanchez-Guerrero Jorge, Wofsy David, Bensley Karen, Kim Lilianne, Lo Kim Hung, Shu Cathye, Shao Jie, Karyekar Chetan S, Diamond Betty
Division of Nephrology, Department of Medicine IV, Hospital of the Ludwig-Maximilians University, Munich, Germany.
Department of Medicine, School of Clinical Medicine at the University of Hong Kong, Hong Kong, China.
Rheumatology (Oxford). 2025 May 1;64(5):2731-2740. doi: 10.1093/rheumatology/keae647.
Evaluate the efficacy and safety of guselkumab, an IL-23p19-subunit inhibitor, in a phase 2, multicentre, randomized, double-blind, placebo-controlled study of patients with active LN.
Adults (18-75 years) with active LN [Class III-IV proliferative nephritis (kidney biopsy) and urine protein-to-creatinine ratio (UPCR) of ≥1 mg/mg despite standard-of-care therapy] were randomized (1:1; planned sample = 60) to receive i.v. infusions of guselkumab 400 mg or placebo at weeks 0, 4 and 8, then s.c. injections (guselkumab 200 mg or placebo) at week 12 and every 4 weeks through week 48 in addition to their background therapy. The primary endpoint was achievement of ≥50% decrease in proteinuria from baseline at week 24. Major secondary endpoints (week 24) were achievement of complete renal response (CRR), sustained reduction in steroid dose (≤10 mg/day prednisone/equivalent) from weeks 16-24, UPCR <0.5 mg/mg; <0.75 mg/mg, time to achieving CRR, and time to treatment failure. Safety was assessed through the end of the study.
Following enrolment challenges (COVID-19 pandemic; Ukraine/Russia crisis), the sponsor terminated the study early; 33 participants were randomized (placebo, n = 16; guselkumab, n = 17). At week 24, 56.3% (9/16) in the placebo group and 35.3% (6/17) in the guselkumab group achieved the primary endpoint. No apparent differences were observed in the secondary endpoints. Through end-of-study, 75% of placebo patients and 71% of guselkumab patients reported ≥1 adverse event; most were of mild-to-moderate severity.
Guselkumab+background therapy did not demonstrate superior reduction in proteinuria vs placebo+background therapy in this small cohort of patients with active LN. Safety results were consistent with the known safety profile of guselkumab.
ClinicalTrials.gov: NCT04376827.
在一项针对活动性狼疮性肾炎（LN）患者的2期多中心随机双盲安慰剂对照研究中，评估白细胞介素-23 p19亚基抑制剂古塞库单抗的疗效和安全性。
将患有活动性LN的成年人（18 - 75岁）[III - IV级增殖性肾炎（肾活检）且尽管接受了标准治疗但尿蛋白肌酐比（UPCR）≥1mg/mg]随机分组（1:1；计划样本量 = 60），在第0、4和8周接受静脉输注400mg古塞库单抗或安慰剂，然后在第12周及之后每4周皮下注射（200mg古塞库单抗或安慰剂），同时继续其基础治疗。主要终点是在第24周时蛋白尿较基线水平降低≥50%。主要次要终点（第24周）包括达到完全肾脏缓解（CRR）、从第16 - 24周类固醇剂量持续降低（≤10mg/天泼尼松/等效剂量）、UPCR < 0.5mg/mg；< 0.75mg/mg、达到CRR的时间以及治疗失败的时间。通过研究结束时评估安全性。
在经历入组挑战（新冠疫情；俄乌危机）后，申办方提前终止了研究；33名参与者被随机分组（安慰剂组，n = 16；古塞库单抗组，n = 17）。在第24周时，安慰剂组56.3%（9/16）和古塞库单抗组35.3%（6/17）达到主要终点。次要终点未观察到明显差异。至研究结束时，75%的安慰剂组患者和71%的古塞库单抗组患者报告了≥1次不良事件；大多数为轻至中度严重程度。
在这一小群活动性LN患者中，与安慰剂 + 基础治疗相比，古塞库单抗 + 基础治疗在降低蛋白尿方面未显示出优势。安全性结果与古塞库单抗已知的安全性特征一致。
ClinicalTrials.gov：NCT04376827。
