一项3期、多中心、随机、安慰剂对照研究，评估优特克单抗治疗系统性红斑狼疮患者的疗效和安全性。
Phase 3, multicentre, randomised, placebo-controlled study evaluating the efficacy and safety of ustekinumab in patients with systemic lupus erythematosus.
作者信息
van Vollenhoven Ronald F, Kalunian Kenneth C, Dörner Thomas, Hahn Bevra H, Tanaka Yoshiya, Gordon Robert M, Shu Cathye, Fei Kaiyin, Gao Sheng, Seridi Loqmane, Gallagher Patrick, Lo Kim Hung, Berry Pamela, Zuraw Qing C
机构信息
Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Amsterdam, The Netherlands
Division of Rheumatology, Allergy and Immunology, University of California San Diego, La Jolla, California, USA.
出版信息
Ann Rheum Dis. 2022 Oct 12;81(11):1556-1563. doi: 10.1136/ard-2022-222858.
OBJECTIVE
Evaluate the efficacy and safety of ustekinumab, an anti-interleukin-12/23 p40 antibody, in a phase 3, randomised, placebo-controlled study of patients with active systemic lupus erythematosus (SLE) despite receiving standard-of-care.
METHODS
Active SLE patients (SLE Disease Activity Index 2000 (SLEDAI-2K) ≥6 during screening and SLEDAI-2K ≥4 for clinical features at week 0) despite receiving oral glucocorticoids, antimalarials, or immunomodulatory drugs were randomised (3:2) to receive ustekinumab (intravenous infusion ~6 mg/kg at week 0, followed by subcutaneous injections of ustekinumab 90 mg at week 8 and every 8 weeks) or placebo through week 48. The primary endpoint was SLE Responder Index (SRI)-4 at week 52, and major secondary endpoints included time to flare through week 52 and SRI-4 at week 24.
RESULTS
At baseline, 516 patients were randomised to placebo (n=208) or ustekinumab (n=308). Following the planned interim analysis, the sponsor discontinued the study due to lack of efficacy but no safety concerns. Efficacy analyses included 289 patients (placebo, n=116; ustekinumab, n=173) who completed or would have had a week 52 visit at study discontinuation. At week 52, 44% of ustekinumab patients and 56% of placebo patients had an SRI-4 response; there were no appreciable differences between the treatment groups in the major secondary endpoints. Through week 52, 28% of ustekinumab patients and 32% of placebo patients had a British Isles Lupus Assessment Group flare, with a mean time to first flare of 204.7 and 200.4 days, respectively. Through week 52, 70% of ustekinumab patients and 74% of placebo patients had ≥1 adverse event.
CONCLUSIONS
Ustekinumab did not demonstrate superiority over placebo in this population of adults with active SLE; adverse events were consistent with the known safety profile of ustekinumab.
TRIAL REGISTRATION NUMBER
NCT03517722.
目的
在一项3期、随机、安慰剂对照研究中，评估抗白细胞介素-12/23 p40抗体优特克单抗对尽管接受了标准治疗但仍患有活动性系统性红斑狼疮（SLE）患者的疗效和安全性。
方法
尽管接受了口服糖皮质激素、抗疟药或免疫调节药物治疗，但活动性SLE患者（筛查时系统性红斑狼疮疾病活动指数2000（SLEDAI-2K）≥6，第0周临床特征的SLEDAI-2K≥4）被随机分组（3:2），接受优特克单抗（第0周静脉输注约6 mg/kg，随后在第8周和每8周皮下注射优特克单抗90 mg）或安慰剂治疗至第48周。主要终点是第52周时的SLE缓解指数（SRI）-4，主要次要终点包括至第52周的疾病复发时间和第24周时的SRI-4。
结果
在基线时，516例患者被随机分配至安慰剂组（n = 208）或优特克单抗组（n = 308）。在计划的中期分析后，由于缺乏疗效，申办方终止了该研究，但无安全性问题。疗效分析纳入了289例患者（安慰剂组，n = 116；优特克单抗组，n = 173），这些患者在研究终止时完成或本应进行第52周访视。在第52周时，44%的优特克单抗组患者和56%的安慰剂组患者有SRI-4反应；在主要次要终点方面，治疗组之间无明显差异。至第52周时，28%的优特克单抗组患者和32%的安慰剂组患者出现不列颠群岛狼疮评估组疾病复发，首次复发的平均时间分别为204.7天和200.4天。至第52周时，70%的优特克单抗组患者和74%的安慰剂组患者发生≥1次不良事件。
结论
在这群患有活动性SLE的成年人中，优特克单抗未显示出优于安慰剂的效果；不良事件与优特克单抗已知的安全性特征一致。
试验注册号
NCT03517722。
Zotero 插件