Trial of Anti-BDCA2 Antibody Litifilimab for Systemic Lupus Erythematosus
Trial of Anti-BDCA2 Antibody Litifilimab for Systemic Lupus Erythematosus
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DOI：
10.1056/nejmoa2118025
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发表时间：
2022-09-08
影响因子：
158.5
通讯作者：
Franchimont, Nathalie
中科院分区：
文献类型：
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作者：
Furie, Richard A.;van Vollenhoven, Ronald F.;Franchimont, Nathalie
背景：血树突状细胞抗原2(BDCA2)的抗体结合能抑制I型干扰素的产生，而I型干扰素参与了系统性红斑狼疮(SLE)的发病。皮下注射人源化抗BDCA2单抗在SLE患者中的安全性和有效性尚未得到广泛研究。最初的试验设计要求随机分配参与者在0周、2周、4周、8周、12周、16周和20周皮下给药，主要终点是评估皮肤狼疮活动。试验设计随后被修改；患有系统性红斑狼疮、关节炎和活动性皮肤病的成年人被随机分配接受450毫克剂量的利非利单抗或安慰剂。修订的主要终点是第24周活动关节总数(定义为肿胀关节和压痛关节的总和)与基线的变化。次要终点是皮肤和全球疾病活动的变化。结果共有334名成年人接受了资格评估，132人接受了随机分组(被分配接受450毫克的利非利单抗，6人接受150毫克的利非利单抗，6人接受50毫克的利非利单抗，56人接受安慰剂)。初步分析是在102名参与者中进行的，这些参与者接受了450毫克的利非利单抗或安慰剂，并且至少有四次疼痛和至少四次关节肿胀。平均(+/-SD)活动关节基线数在liphilimab组为19.0+/-8.4，在安慰剂组为21.6+/-8.5。从基线到第24周，活动关节总数的最小二乘均值(+/-SE)变化，利非利单抗为-15.0+/-1.2，安慰剂为-11.6+/-1.3(平均差异-3.4；95%可信区间-6.7至-0.2；P=0.04)。大多数次要终点不支持主要终点的分析结果。在一项涉及系统性红斑狼疮参与者的2期试验中，在为期24周的试验中，与安慰剂相比，接受litifilimab的患者关节肿胀和压痛的数量减少得更多。需要更长时间和更大规模的试验来确定司非利单抗治疗系统性红斑狼疮的安全性和有效性。
BACKGROUNDAntibody-binding of blood dendritic cell antigen 2 (BDCA2), which is expressed exclusively on plasmacytoid dendritic cells, suppresses the production of type I interferon that is involved in the pathogenesis of systemic lupus erythematosus (SLE). The safety and efficacy of subcutaneous litifilimab, a humanized monoclonal antibody that binds to BDCA2, in patients with SLE have not been extensively studied.METHODSWe conducted a phase 2 trial of litifilimab involving participants with SLE. The initial trial design called for randomly assigning participants to receive litifilimab (at a dose of 50, 150, or 450 mg) or placebo administered subcutaneously at weeks 0, 2, 4, 8, 12, 16, and 20, with the primary end point of evaluating cutaneous lupus activity. The trial design was subsequently modified; adults with SLE, arthritis, and active skin disease were randomly assigned to receive either litifilimab at a dose of 450 mg or placebo. The revised primary end point was the change from baseline in the total number of active joints (defined as the sum of the swollen joints and the tender joints) at week 24. Secondary end points were changes in cutaneous and global disease activity. Safety was also assessed.RESULTSA total of 334 adults were assessed for eligibility, and 132 underwent randomization (64 were assigned to receive 450-mg litifilimab, 6 to receive 150-mg litifilimab, 6 to receive 50-mg litifilimab, and 56 to receive placebo). The primary analysis was conducted in the 102 participants who had received 450-mg litifilimab or placebo and had at least four tender and at least four swollen joints. The mean (+/- SD) baseline number of active joints was 19.0 +/- 8.4 in the litifilimab group and 21.6 +/- 8.5 in the placebo group. The least-squares mean (+/- SE) change from baseline to week 24 in the total number of active joints was -15.0 +/- 1.2 with litifilimab and -11.6 +/- 1.3 with placebo (mean difference, -3.4; 95% confidence interval, -6.7 to -0.2; P=0.04). Most of the secondary end points did not support the results of the analysis of the primary end point. Receipt of litifilimab was associated with adverse events, including two cases of herpes zoster and one case of herpes keratitis.CONCLUSIONSIn a phase 2 trial involving participants with SLE, litifilimab was associated with a greater reduction from baseline in the number of swollen and tender joints than placebo over a period of 24 weeks. Longer and larger trials are required to determine the safety and efficacy of litifilimab for the treatment of SLE.