Liu Meng, Yin Pan, Fan Ruihan, Zhang Guanfei, Zhao Kaidi
Department of Dermatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
Frontier Institute of Science and Technology, and Interdisciplinary Research Center of Frontier Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Sci Rep. 2025 Aug 5;15(1):28529. doi: 10.1038/s41598-025-13502-5.
Certolizumab pegol (CZP), a PEGylated anti-tumor necrosis factor alpha (TNF-α) biologic, is approved for treating autoimmune disorders, including psoriatic arthritis (PsA). Despite its good therapeutic effects, its real-world safety remains limited. This study aims to evaluate the real-world safety of CZP using the FDA Adverse Event Reporting System (FAERS). We collected FAERS data from Q2 2008 to Q4 2024 related to adverse event reports associated with CZP. Four disproportionality analysis methods were used to explore the relationship between CZP and adverse events (AEs), including: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). Additionally, the study analyzed the time to onset of AEs. A total of 78,143 reports listed CZP as the primary suspect (PS), with 216,522 associated AEs. CZP-induced AEs spanned 24 system organ classes (SOCs). The median time to onset for AEs was 92 days (interquartile range: 3-409 days). At the PT level, a total of 322 AE signals were identified as positive, with known positive events including infections and infestations, general disorders, administration site conditions, and musculoskeletal and connective tissue disorders. Additionally, unexpected positive AEs, such as spontaneous abortion, premature birth, pemphigus, and basal cell carcinoma, were identified. This study systematically evaluated the safety of CZP using the FAERS database, confirming some known AEs and revealing unexpected AEs. This post-marketing safety evaluation has deepened our understanding of the safety profile of CZP, and prospective studies are needed to validate the findings of this study.
聚乙二醇化抗肿瘤坏死因子α（TNF-α）生物制剂赛妥珠单抗（CZP）已被批准用于治疗包括银屑病关节炎（PsA）在内的自身免疫性疾病。尽管其治疗效果良好，但其实际应用中的安全性仍存在局限性。本研究旨在使用美国食品药品监督管理局不良事件报告系统（FAERS）评估CZP的实际应用安全性。我们收集了2008年第二季度至2024年第四季度与CZP相关不良事件报告的FAERS数据。使用四种不成比例分析方法来探究CZP与不良事件（AE）之间的关系，包括：报告比值比（ROR）、比例报告比（PRR）、贝叶斯置信传播神经网络（BCPNN）和多项目伽马泊松收缩器（MGPS）。此外，该研究分析了不良事件的发病时间。共有78,143份报告将CZP列为主要怀疑对象（PS），涉及216,522起相关不良事件。CZP引发的不良事件涵盖24个系统器官类别（SOC）。不良事件的发病中位时间为92天（四分位间距：3 - 409天）。在首选术语（PT）层面，共识别出322个阳性不良事件信号，已知的阳性事件包括感染和寄生虫感染、全身性疾病、给药部位情况以及肌肉骨骼和结缔组织疾病。此外，还识别出了意外的阳性不良事件，如自然流产、早产、天疱疮和基底细胞癌。本研究使用FAERS数据库系统地评估了CZP的安全性，证实了一些已知的不良事件并揭示了意外的不良事件。这项上市后安全性评估加深了我们对CZP安全性概况的理解，需要进行前瞻性研究以验证本研究的结果。
