近日，北京协和医学院附属医院张奉春团队研究了泰它西普治疗系统性红斑狼疮的3期临床试验效果。2025年10月16日，《新英格兰医学杂志》发表了这一成果。

泰它西普是一种新的细胞因子b淋巴细胞刺激剂（BLyS）和APRIL（一种增殖诱导配体）的双重抑制剂，在一项2b期临床试验中，它在标准治疗中显示出对成人活动性系统性红斑狼疮（SLE）的疗效。

研究组在中国开展了一项三期临床试验，将活动性系统性红斑狼疮（SLE）受试者按1:1比例随机分组，在标准治疗基础上分别每周一次皮下注射泰它西普（160毫克）或安慰剂，持续52周。主要终点为第52周时达到改良版SLE应答指数4（SRI-4）应答标准，该复合指标要求：狼疮雌激素安全性评估-系统性红斑狼疮疾病活动指数（SELENA-SLEDAI）评分降低≥4分（该评分范围0-105分，分值越高表示疾病活动度越强），不列颠群岛狼疮评估组指数未见新的疾病活动，且医师总体评估无恶化。

在完成筛查的433名成人患者中，共有335例接受随机分组（泰它西普组167例，安慰剂组168例）。第52周时，泰它西普组达到改良SRI-4应答标准的受试者比例显著高于安慰剂组（67.1% vs 32.7%；校正后差异为34.5个百分点，95%置信区间[CI]为24.3-44.7，P<0.001）。泰它西普组SELENA-SLEDAI评分较基线降低≥4分的患者比例为70.1%，安慰剂组为40.5%（差异为29.6个百分点，95%CI为13.1-46.1）。研究者判定与试验方案相关的不良事件发生率在泰它西普组更高（74.9% vs 50.0%），其中上呼吸道感染（31.7% vs 19.0%）、血清IgG水平降低（15.6% vs 1.2%）、血清IgM水平降低（15.0% vs 0.6%）及注射部位反应（12.6% vs 0.6%）在泰它西普组更常见。

在这项为期52周的试验中，涉及正在接受背景治疗的活动性SLE参与者，泰它西普的临床缓解发生率高于安慰剂。然而，使用泰它西普后，上呼吸道感染、免疫球蛋白水平降低和注射部位反应的发生率也更高。

附：英文原文

Title: A Phase 3 Trial of Telitacicept for Systemic Lupus Erythematosus

Author: Ronald F. van Vollenhoven, Li Wang, Joan T. Merrill, Yi Liu, Chunde Bao, Fen Li, Jiankang Hu, Chenghui Huang, Jianhong Zhao, Cibo Huang, Hanyou Mo, Wei Wei, Fu’ai Lu, Jingyang Li, Dongbao Zhao, Wenxiang Wang, Lin Li, Qing Zuraw, Xiaofei Wang, Xuebin Wang, Jianmin Fang, Fengchun Zhang

Issue&Volume: 2025-10-16

Abstract:

BACKGROUND

Telitacicept, a new dual inhibitor of the cytokines B-lymphocyte stimulator (BLyS) and APRIL (a proliferation-inducing ligand), showed efficacy in adults with active systemic lupus erythematosus (SLE) in a phase 2b trial when added to standard therapy.

METHODS

We conducted a phase 3 trial in China in which participants with active SLE were randomly assigned (in a 1:1 ratio) to receive telitacicept (160 mg) or placebo subcutaneously once weekly for 52 weeks, in addition to standard therapy. The primary end point at week 52 was a response on the modified SLE Responder Index 4 (SRI-4), with a response on this composite measure defined as a reduction of at least 4 points in the Safety of Estrogens in Lupus Erythematosus National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score (ranging from 0 to 105, with higher scores indicating greater disease activity), no new disease activity as measured on the British Isles Lupus Assessment Group index, and no worsening in the Physician’s Global Assessment score.

RESULTS

Of 433 adults screened, 335 underwent randomization (167 to the telitacicept group and 168 to the placebo group). At week 52, significantly more participants receiving telitacicept had a response on the modified SRI-4 than those receiving placebo (67.1% vs. 32.7%; adjusted difference, 34.5 percentage points; 95% confidence interval [CI], 24.3 to 44.7; P<0.001). A reduction of at least 4 points from baseline in the SELENA-SLEDAI score had occurred in 70.1% of the telitacicept group and in 40.5% of the placebo group (difference, 29.6 percentage points; 95% CI, 13.1 to 46.1). Adverse events that were considered by the investigator to be related to the trial regimen were more common with telitacicept than with placebo (74.9% vs. 50.0%). Such events that occurred more frequently in the telitacicept group than in the placebo group included upper respiratory tract infection (31.7% vs. 19.0%), a reduced serum IgG level (15.6% vs. 1.2%), a reduced serum IgM level (15.0% vs. 0.6%), and injection-site reactions (12.6% vs. 0.6%).

CONCLUSIONS

In this 52-week trial involving participants with active SLE who were receiving background therapy, the incidence of a clinical response was higher with telitacicept than with placebo. However, the incidence of upper respiratory infections, reduced immunoglobulin levels, and injection-site reactions was also higher with telitacicept.

DOI: NJ202510163931508

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2414719