Matera Maria Gabriella, Ora Josuel, Calzetta Luigino, Rogliani Paola, Cazzola Mario
Unit of Pharmacology, Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.
Division of Respiratory Medicine, University Hospital "Fondazione Policlinico Tor Vergata", Rome, Italy.
J Asthma. 2024 Sep;61(9):905-911. doi: 10.1080/02770903.2024.2311236. Epub 2024 Feb 7.
Modification of the immune system with biologics raises theoretical concerns about the risk of infections but it is still unclear whether currently routinely used biologics in severe asthma may facilitate the development of pneumonia. Therefore, we aimed to determine whether omalizumab, mepolizumab, benralizumab, and dupilumab are associated with pneumonia in a real-world setting.
A retrospective disproportionality analysis was performed using adverse event (AE) reports submitted to FAERS from January 2020 to September 30, 2023. MedDRA was used to identify infections and infestations and then pneumonia cases. ROR and PRR were used to measure disproportionality.
The percentage of reported cases of pneumonia compared to infections and infestations was highest for mepolizumab (36.8%), followed by omalizumab (32.6%), benralizumab (19.2%) and dupilumab (5.7%). We found a moderate or strong signal for increased risk of pneumonia with mepolizumab (ROR = 3.74, 95%CI 3.50-4.00), omalizumab (ROR = 3.26, 95%CI 3.06-3.49) and benralizumab (ROR = 2.65, 95%CI 2.49-2.83).
Mepolizumab, omalizumab and benralizumab, but not dupilumab, were associated with high odds of reporting pneumonia. Our results represent only potential associations between these biologics and pneumonia but not causality. The nature of the FAERS database is such that the cause of the reported events is uncertain. Therefore, we can only roughly estimate the incidence of AEs by the signal strength (ROR value). Nevertheless, although causality could not be assessed, the signal from our study is interesting. We believe it deserves to be further substantiated by real-world studies with robust designs.
使用生物制剂调节免疫系统引发了对感染风险的理论担忧，但目前尚不清楚重度哮喘中常规使用的生物制剂是否会促进肺炎的发生。因此，我们旨在确定在现实环境中，奥马珠单抗、美泊利单抗、贝那利珠单抗和度普利尤单抗是否与肺炎相关。
使用2020年1月至2023年9月30日提交给美国食品药品监督管理局不良事件报告系统（FAERS）的报告进行回顾性不成比例分析。使用医学术语词典（MedDRA）识别感染和寄生虫感染，然后确定肺炎病例。使用报告比值比（ROR）和比例报告比值（PRR）来衡量不成比例性。
与感染和寄生虫感染相比，美泊利单抗报告的肺炎病例百分比最高（36.8%），其次是奥马珠单抗（32.6%）、贝那利珠单抗（19.2%）和度普利尤单抗（5.7%）。我们发现美泊利单抗（ROR = 3.74，95%置信区间3.50 - 4.00）、奥马珠单抗（ROR = 3.26，95%置信区间3.06 - 3.49）和贝那利珠单抗（ROR = 2.65，95%置信区间2.49 - 2.83）有中度或强烈信号表明肺炎风险增加。
美泊利单抗、奥马珠单抗和贝那利珠单抗，而非度普利尤单抗，与报告肺炎的高可能性相关。我们的结果仅代表这些生物制剂与肺炎之间的潜在关联，而非因果关系。FAERS数据库的性质使得报告事件的原因不确定。因此，我们只能通过信号强度（ROR值）大致估计不良事件的发生率。然而，尽管无法评估因果关系，但我们研究中的信号很有意思。我们认为值得通过设计严谨的现实研究进一步证实。
