托珠单抗在儿科患者中的安全性信号：基于FAERS数据库的真实世界药物警戒分析及网络药理学见解。
Safety signals of tocilizumab in pediatric patients: A real-world pharmacovigilance analysis based on the FAERS database with network pharmacology insights.
文献信息
| PMID | 42873988 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Gang Wu |
| 作者单位 | Department of Pediatrics, Yancheng Maternal and Child Health Care Hospital Affiliated to Yangzhou University, Yancheng, China. |
| 期刊 | Human vaccines & immunotherapeutics |
| SCI 分区 | Q2 |
| IF | 3.7 |
| 研究类型 | 临床研究 · 临床 |
| 所属专科 | 耳科 |
中文摘要
托珠单抗是一种靶向白细胞介素-6受体的人源化单克隆抗体，广泛用于免疫介导性疾病，但其在儿科人群中的真实世界安全性仍未被充分描述。这项回顾性药物警戒研究分析了美国食品药品监督管理局不良事件报告系统（FAERS）数据库（2010-2025年）中的不良事件（AE）报告，重点关注托珠单抗为主要可疑药物的儿科病例。数据清洗后，共纳入1,485份报告。采用四种经典的不比例分析方法——报告比值比（ROR）、比例报告比（PRR）、贝叶斯置信传播神经网络（BCPNN）和多伽马泊松收缩器（MGPS）——来识别安全性信号。应用发病时间、分层和Weibull分析来表征不良事件模式，并使用网络药理学探索潜在机制。女性占报告的58.9%，12-17岁青少年是最大的群体。共识别出109个安全性信号。最常报告的不良事件包括幼年特发性关节炎（ROR = 28.62，95% CI：24.30-33.72）、噬血细胞性淋巴组织细胞增生症（ROR = 15.83，95% CI：13.18-19.02）和白细胞计数减少（ROR = 12.14，95% CI：9.90-14.88）。还检测到潜在未列出的不良事件，如突发性听力损失（ROR = 48.11，95% CI：16.74-138.26）和银屑病（ROR = 11.44，95% CI：8.81-14.85）。大多数不良事件发生在30天内，中位发病时间为14天，并显示出早期失败模式。网络药理学提示银屑病可能涉及JAK-STAT和Th17/Th1通路，但需要进一步验证。总体而言，本研究提供了真实世界证据，以支持改善儿科患者的安全性监测。
英文摘要
Tocilizumab, a humanized monoclonal antibody targeting the interleukin-6 receptor, is widely used in immune-mediated diseases, yet its real-world safety in pediatric populations remains insufficiently characterized. This retrospective pharmacovigilance study analyzed adverse event (AE) reports from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database (2010-2025), focusing on pediatric cases where tocilizumab was the primary suspect drug. After data cleaning, 1,485 reports were included. Four classical disproportionality methods - reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multiple gamma Poisson shrinker (MGPS) - were used to identify safety signals. Time-to-onset, stratified, and Weibull analyses were applied to characterize adverse event patterns, and network pharmacology was used to explore potential underlying mechanisms. Females accounted for 58.9% of reports, and adolescents aged 12-17 years represented the largest group. A total of 109 safety signals were identified. The most frequently reported AEs included juvenile idiopathic arthritis (ROR = 28.62, 95% CI: 24.30-33.72), haemophagocytic lymphohistiocytosis (ROR = 15.83, 95% CI: 13.18-19.02), and decreased white blood cell count (ROR = 12.14, 95% CI: 9.90-14.88). Potential unlisted AEs, such as sudden hearing loss (ROR = 48.11, 95% CI: 16.74-138.26) and psoriasis (ROR = 11.44, 95% CI: 8.81-14.85), were also detected. Most AEs occurred within 30 days, with a median onset of 14 days, and showed an early failure pattern. Network pharmacology suggested psoriasis may involve JAK-STAT and Th17/Th1 pathways, though further validation is needed. Overall, this study provides real-world evidence to support improved safety monitoring in pediatric patients.