Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
School of Pharmacy, Lanzhou University, Lanzhou, Gansu Province, China.
Expert Opin Drug Saf. 2024 Mar;23(3):353-362. doi: 10.1080/14740338.2023.2251382. Epub 2023 Aug 29.
Anti-IL-5 monoclonal antibodies (mAbs) targeting IL-5 or IL-5 R α (including mepolizumab, benralizumab, and reslizumab) are widely used for inflammatory diseases such as asthma, eosinophilia, and polyangiitis. However, real-world data regarding its safety in a large sample population are incomplete. So, we evaluated the safety of anti-IL-5 mAbs by pharmacovigilance analyzes based on related adverse events (AEs) from the FDA Adverse Event Reporting System (FAERS).
In disproportionality analysis, four algorithms were employed to detect the signals of anti-IL-5 mAbs from the FAERS between 2016 and 2022. In addition, we also used MYSQL 8.0, Navicat Premium 15, and Microsoft EXCEL 2019 to analyze the signals of anti-IL-5 mAbs systematically.
There are 9,476,351 reports collected from the FAERS database, of which 22,174 reports listed anti-IL-5 mAbs as the 'primary suspected (PS)' drug. A total of 59 (20 new signals, mepolizumab) and 62 (19 new signals, benralizumab) significant disproportionality preferred terms (PTs) conforming to the four algorithms were retained synchronously. Finally, we detected that the anti-IL-5 mAbs-induced AEs occurred in 31 organ systems (mepolizumab) and 30 organ systems (benralizumab). For mepolizumab and reslizumab, unexpected and new significant PTs of AEs were found, such as asthmatic crisis, chronic obstructive pulmonary disease (COPD), pneumonia, COVID-19, pneumothorax, adrenal insufficiency and so on. Notably, the risk signal of asthmatic crisis for mepolizumab was stronger than benralizumab (ROR 108.04 [95%CI, 96.09-121.47] vs 26.83 [95%CI, 18.91-38.06]). Comparing with mepolizumab and benralizumab, we found the proportion of serious adverse events in mepolizumab was both greater than benralizumab in each age group (≤20, 20-65, and ≥ 65). The median onset time of mepolizumab was 280 days (interquartile range [IQR] 1-367 days).
Analysis of FAERS data identified anti-IL-5 mAbs-associated AEs, and our findings supported continuous clinical monitoring, pharmacovigilance, and further studies of anti-IL-5 mAbs. In addition, clinicians may be more aware of the limitations of use in package inserts of anti-IL-5 mAbs: Not for relief of acute bronchospasm or status asthmaticus. Because of some limitations in the FAERS such as self-reports from patients and other confounding factors, the safety of anti-IL-5 mAbs needed more studies in different dimensions, especially the risk of cancer.
靶向白细胞介素 5（IL-5）或 IL-5 受体 α（包括美泊利珠单抗、贝那利珠单抗和瑞利珠单抗）的抗 IL-5 单克隆抗体（mAb）广泛用于哮喘、嗜酸性粒细胞增多症和多血管炎等炎症性疾病。然而，关于其在大样本人群中的安全性的真实世界数据并不完整。因此，我们通过基于美国食品药品监督管理局不良事件报告系统（FAERS）中相关不良事件（AE）的药物警戒分析来评估抗 IL-5 mAb 的安全性。
在比例失调分析中，我们使用了四种算法来检测 2016 年至 2022 年期间 FAERS 中抗 IL-5 mAb 的信号。此外，我们还使用 MySQL 8.0、Navicat Premium 15 和 Microsoft EXCEL 2019 来系统地分析抗 IL-5 mAb 的信号。
从 FAERS 数据库中收集到 9476351 份报告，其中 22174 份报告将抗 IL-5 mAb 列为“主要怀疑（PS）”药物。同时保留了 59 个（20 个新信号，美泊利珠单抗）和 62 个（19 个新信号，贝那利珠单抗）符合四种算法的显著比例失调首选术语（PT）。最后，我们发现抗 IL-5 mAb 引起的 AE 发生在 31 个器官系统（美泊利珠单抗）和 30 个器官系统（贝那利珠单抗）中。对于美泊利珠单抗和瑞利珠单抗，我们发现了一些意外的新的 AE 显著 PT，如哮喘危象、慢性阻塞性肺疾病（COPD）、肺炎、COVID-19、气胸、肾上腺功能不全等。值得注意的是，美泊利珠单抗的哮喘危象风险信号强于贝那利珠单抗（RR 108.04[95%CI，96.09-121.47]vs 26.83[95%CI，18.91-38.06]）。与美泊利珠单抗和贝那利珠单抗相比，我们发现美泊利珠单抗在每个年龄组（≤20 岁、20-65 岁和≥65 岁）的严重不良事件比例均大于贝那利珠单抗。美泊利珠单抗的中位发病时间为 280 天（IQR 1-367 天）。
FAERS 数据分析确定了抗 IL-5 mAb 相关的 AE，我们的研究结果支持对抗 IL-5 mAb 进行持续的临床监测、药物警戒和进一步研究。此外，临床医生可能会更加意识到抗 IL-5 mAb 说明书使用限制的局限性：不适用于缓解急性支气管痉挛或哮喘持续状态。由于 FAERS 存在一些局限性，例如来自患者的自我报告和其他混杂因素，因此需要在不同维度，特别是癌症风险方面，对抗 IL-5 mAb 的安全性进行更多研究。
