Capogrosso Sansone Alice, Mantarro Stefania, Tuccori Marco, Ruggiero Elisa, Montagnani Sabrina, Convertino Irma, Marino Alessandra, Fornai Matteo, Antonioli Luca, Corona Tiberio, Garibaldi Danila, Blandizzi Corrado
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Pharmaceutical Unit, Health District of Lucca, Lucca, Italy.
Drug Saf. 2015 Oct;38(10):869-88. doi: 10.1007/s40264-015-0336-2.
Certolizumab pegol (CZP), an anti-tumor necrosis factor PEGylated Fab' fragment of a humanized monoclonal antibody, is currently approved for treatment of some immune-mediated inflammatory diseases (IMIDs). To our knowledge, no systematic review and meta-analysis evaluating the overall safety profile of CZP has been performed.
The objective of this systematic review was to assess the adverse event (AE) patterns of CZP versus a control in patients with IMIDs.
A systematic literature search was performed using PubMed/MEDLINE, EMBASE, the Cochrane Library, and the FDA database for clinical trials up to March 2014. Eligible studies were those that compared the safety profile of CZP to a control group in patients with IMIDs. The following data were extracted: number of patients experiencing AEs, serious AEs (SAEs), adverse drug reactions (ADRs), withdrawals due to AEs, fatal AEs, infectious AEs and SAEs, upper respiratory tract infections, injection-site reactions, neoplasms, and tuberculosis.
A total of 2023 references were identified and 18 randomized controlled trials were included. The main pooled risk ratios of CZP-treated versus control patients were as follows: AEs 1.09 (95% confidence interval, CI 1.04-1.14), SAEs 1.50 (95% CI 1.21-1.86), ADRs 1.20 (95% CI 1.03-1.39), infectious AEs 1.28 (95% CI 1.13-1.45), infectious SAEs 2.17 (95% CI 1.36-3.47), and upper respiratory tract infections 1.34 (95% CI 1.15-1.57).
Safety data on CZP suggest an overall favorable tolerability profile, with infections being the most common AE. However, CZP-treated patients had a twofold higher risk of infectious SAEs than control patients. Large observational studies and data from national registries are needed to detect rare AEs, which might occur after long-term exposures to CZP.
赛妥珠单抗（CZP）是一种人源化单克隆抗体的抗肿瘤坏死因子聚乙二醇化Fab'片段，目前已被批准用于治疗某些免疫介导的炎症性疾病（IMID）。据我们所知，尚未对赛妥珠单抗的总体安全性进行系统评价和荟萃分析。
本系统评价的目的是评估赛妥珠单抗与对照组相比在IMID患者中的不良事件（AE）模式。
利用PubMed/MEDLINE、EMBASE、Cochrane图书馆和FDA数据库对截至2014年3月的临床试验进行系统文献检索。符合条件的研究是那些在IMID患者中将赛妥珠单抗的安全性与对照组进行比较的研究。提取了以下数据：发生AE的患者数量、严重AE（SAE）、药物不良反应（ADR）、因AE停药、致命AE、感染性AE和SAE、上呼吸道感染、注射部位反应、肿瘤和结核病。
共识别出2023篇参考文献，纳入18项随机对照试验。赛妥珠单抗治疗组与对照组患者的主要合并风险比如下：AE为1.09（95%置信区间，CI 1.04-1.14），SAE为1.50（95%CI 1.21-1.86），ADR为1.20（95%CI 1.03-1.39），感染性AE为1.28（95%CI 1.13-1.45），感染性SAE为2.17（95%CI 1.36-3.47），上呼吸道感染为1.34（95%CI 1.15-1.57）。
赛妥珠单抗的安全性数据表明其总体耐受性良好，感染是最常见的AE。然而，赛妥珠单抗治疗的患者发生感染性SAE的风险是对照组患者的两倍。需要进行大型观察性研究和国家登记数据来检测长期使用赛妥珠单抗后可能出现的罕见AE。
