美国Biogen制药公司Nathalie Franchimont团队研究了抗BDCA2抗体lifilimab治疗系统性红斑狼疮的疗效与安全性。相关论文发表在2022年9月7日出版的《新英格兰医学杂志》上。

血液树突状细胞抗原2（BDCA2）的抗体结合抑制了参与系统性红斑狼疮（SLE）发病机制的I型干扰素的产生，该抗原仅在浆细胞样树突状上皮细胞上表达。皮下注射litifilimab（一种结合BDCA2的人源化单克隆抗体）在SLE患者中的安全性和有效性尚未得到广泛研究。

研究组进行了litifilimab的2期临床试验，参与者包括系统性红斑狼疮患者。最初的试验设计要求随机分配参与者在第0、2、4、8、12、16和20周接受皮下注射litifilimab（剂量为50、150或450 mg）或安慰剂，主要终点为评估皮肤狼疮活动性。

随后改良了试验设计；患有系统性红斑狼疮、关节炎和活动性皮肤病的成人被随机分配接受450 mg剂量的litifilimab或安慰剂。修订的主要终点是第24周活动性关节总数（定义为肿胀关节和压痛关节之和）与基线相比的变化。次要终点是皮肤和全身疾病活动性的变化。还评估了安全性。

研究组共评估了334名成年人的合格性，其中132名接受了随机分组（64名接受450 mg litifilimab，6名接受150 mg litifilimab，5名接受50 mg litifilimab，56名接受安慰剂）。主要分析在102名接受450 mg litifilimab或安慰剂治疗的参与者中进行，他们至少有四个关节压痛和至少四个关节肿胀。

Lifilimab组和安慰剂组的活动性关节平均（±SD）基线数分别为19.0±8.4和21.6±8.5。从基线到第24周活动性关节总数的最小二乘平均值变化在litifilimab组为-15.0±1.2，安慰剂组为-11.6±1.3，组间差异显著。大多数次要终点不支持主要终点的分析结果。接受litifilimab导致不良事件，包括2例带状疱疹和1例疱疹角膜炎。

研究结果表明，在涉及系统性红斑狼疮参与者的2期临床试验中，在24周内，litifilimab与基线相比，肿胀和关节压痛的数量减少更多。但仍需更长时间和更大规模的试验来确定litifilimab治疗系统性红斑狼疮的安全性和有效性。

附：英文原文

Title: Trial of Anti-BDCA2 Antibody Litifilimab for Systemic Lupus Erythematosus

Author: Richard A. Furie, M.D.,, Ronald F. van Vollenhoven, M.D.,, Kenneth Kalunian, M.D.,, Sandra Navarra, M.D.,, Juanita Romero-Diaz, M.D.,, Victoria P. Werth, M.D.,, Xiaobi Huang, Ph.D.,, George Clark, B.S.,, Hua Carroll, M.D.,, Adam Meyers, M.S.,, Cristina Musselli, M.D.,, Catherine Barbey, Ph.D.,, and Nathalie Franchimont, M.D., Ph.D.

Issue&Volume: 2022-09-07

Abstract: Background

Antibody-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.

Methods

We 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.

Results

A 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.

Conclusions

In 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.

DOI: 10.1056/NEJMoa2118025

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2118025