本文由小咖机器人翻译整理

期刊来源：Nat Med

原文链接：https://doi.org/10.1038/s41591-024-03009-3

摘要内容如下：

舍格伦病（SJD）是一种慢性、全身性自身免疫性疾病，目前尚无已获批准的疾病改善疗法。Dazodalibep（DAZ）是一种新型的非抗体融合蛋白，是一种CD40配体拮抗剂，可阻断T细胞和B细胞与抗原呈递细胞之间的共刺激信号，从而抑制SJD中驱动自身免疫的广谱细胞和体液反应。本研究是一项DAZ的第二阶段、随机、双盲、安慰剂（PBO）对照试验，在两个不同的SJD参与者人群中进行交叉阶段。人群1具有中度至重度全身性疾病活动，人群2具有不可接受的症状负担和有限的全身器官受累。所有参与者均诊断为SJD，人群1和2中分别有21.6%和10.1%患有相关的结缔组织疾病（类风湿性关节炎或系统性红斑狼疮）。其余参与者将被视为患有原发性干燥综合征。人群1（n=74）的主要终点是第169天欧洲抗风湿联盟干燥综合征疾病活动指数相对于基线的变化。人群2（n=109）的主要终点是第169天欧洲抗风湿联盟干燥综合征患者报告指数相对于基线的变化。主要终点（最小二乘均数±标准误差）在两个群体1（DAZ，-6.3±0.6；PbO，-4.1±0.6；P=0.0167）和群体2（DAZ，-1.8±0.2；PbO，-0.5±0.2；P=0.0002）。DAZ总体上是安全的，耐受性良好。最常报告的不良事件包括COVID-19、腹泻、头痛、鼻咽炎、上呼吸器官感染、关节痛、便秘和尿路感染。总之，DAZ似乎是治疗SJD的一种潜在的新疗法，其疗效暗示了CD40/CD40配体途径在其发病机制中的重要作用。ClinicalTrials.gov标识符：NCT04129164。

英文原文如下：

Abstracts

Sjögren's disease (SjD) is a chronic, systemic autoimmune disease with no approved disease-modifying therapies. Dazodalibep (DAZ), a novel nonantibody fusion protein, is a CD40 ligand antagonist that blocks costimulatory signals between T and B cells and antigen-presenting cells, and therefore may suppress the wide spectrum of cellular and humoral responses that drive autoimmunity in SjD. This study was a phase 2, randomized, double-blinded, placebo (PBO)-controlled trial of DAZ with a crossover stage in two distinct populations of participants with SjD. Population 1 had moderate-to-severe systemic disease activity and population 2 had an unacceptable symptom burden and limited systemic organ involvement. All participants had a diagnosis of SjD, with 21.6% and 10.1% having an associated connective tissue disease (rheumatoid arthritis or systemic lupus erythematosus) in populations 1 and 2, respectively. The remaining participants would be considered as having primary Sjögren's syndrome. The primary endpoint for population 1 (n = 74) was the change from baseline in the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index at day 169. The primary endpoint for population 2 (n = 109) was the change from baseline in the European League Against Rheumatism Sjögren's Syndrome Patient Reported Index at day 169. The primary endpoints (least squares mean ± standard error) were achieved with statistical significance for both population 1 (DAZ, -6.3 ± 0.6; PBO, -4.1 ± 0.6; P = 0.0167) and population 2 (DAZ, -1.8 ± 0.2; PBO, -0.5 ± 0.2; P = 0.0002). DAZ was generally safe and well tolerated. Among the most frequently reported adverse events were COVID-19, diarrhea, headache, nasopharyngitis, upper respiratory tract infection, arthralgia, constipation and urinary tract infection. In summary, DAZ appears to be a potential new therapy for SjD and its efficacy implies an important role for the CD40/CD40 ligand pathway in its pathogenesis. ClinicalTrials.gov identifier: NCT04129164 .

-----------分割线---------

点击链接：https://www.mediecogroup.com/community/user/vip/categories/ ，成为医咖会员，获取12项专属权益。