Pera Victor, Brusselle Guy G, Riemann Sebastian, Kors Jan A, Van Mulligen Erik M, Parry Rowan, de Wilde Marcel, Rijnbeek Peter R, Verhamme Katia M C
Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, Netherlands.
Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
Front Pharmacol. 2023 Nov 14;14:1276340. doi: 10.3389/fphar.2023.1276340. eCollection 2023.
Monoclonal antibodies (mAbs) targeting immunoglobulin E (IgE) [omalizumab], type 2 (T2) cytokine interleukin (IL) 5 [mepolizumab, reslizumab], IL-4 Receptor (R) α [dupilumab], and IL-5R [benralizumab]), improve quality of life in patients with T2-driven inflammatory diseases. However, there is a concern for an increased risk of helminth infections. The aim was to explore safety signals of parasitic infections for omalizumab, mepolizumab, reslizumab, dupilumab, and benralizumab. Spontaneous reports were used from the Food and Drug Administration's Adverse Event Reporting System (FAERS) database from 2004 to 2021. Parasitic infections were defined as any type of parasitic infection term obtained from the Standardised Medical Dictionary for Regulatory Activities (MedDRA). Safety signal strength was assessed by the Reporting Odds Ratio (ROR). 15,502,908 reports were eligible for analysis. Amongst 175,888 reports for omalizumab, mepolizumab, reslizumab, dupilumab, and benralizumab, there were 79 reports on parasitic infections. Median age was 55 years (interquartile range 24-63 years) and 59.5% were female. Indications were known in 26 (32.9%) reports; 14 (53.8%) biologicals were reportedly prescribed for asthma, 8 (30.7%) for various types of dermatitis, and 2 (7.6%) for urticaria. A safety signal was observed for each biological, except for reslizumab (due to lack of power), with the strongest signal attributed to benralizumab (ROR = 15.7, 95% Confidence Interval: 8.4-29.3). Parasitic infections were disproportionately reported for mAbs targeting IgE, T2 cytokines, or T2 cytokine receptors. While the number of adverse event reports on parasitic infections in the database was relatively low, resulting safety signals were disproportionate and warrant further investigation.
靶向免疫球蛋白E（IgE）的单克隆抗体（mAb）[奥马珠单抗]、2型（T2）细胞因子白细胞介素（IL）-5[美泊利单抗、瑞利珠单抗]、IL-4受体（R）α[度普利尤单抗]和IL-5受体[贝那利珠单抗]可改善T2驱动的炎症性疾病患者的生活质量。然而，人们担心蠕虫感染的风险会增加。目的是探索奥马珠单抗、美泊利单抗、瑞利珠单抗、度普利尤单抗和贝那利珠单抗的寄生虫感染安全信号。使用了美国食品药品监督管理局不良事件报告系统（FAERS）数据库2004年至2021年的自发报告。寄生虫感染定义为从标准化监管活动医学词典（MedDRA）中获得的任何类型的寄生虫感染术语。通过报告比值比（ROR）评估安全信号强度。15502908份报告符合分析条件。在175888份关于奥马珠单抗、美泊利单抗、瑞利珠单抗、度普利尤单抗和贝那利珠单抗的报告中，有79份关于寄生虫感染的报告。中位年龄为55岁（四分位间距24 - 63岁），59.5%为女性。26份（32.9%）报告中的适应证已知；据报道，14份（53.8%）生物制剂用于哮喘，8份（30.7%）用于各种类型的皮炎，2份（7.6%）用于荨麻疹。除瑞利珠单抗（由于效力不足）外，每种生物制剂均观察到安全信号，最强的信号归因于贝那利珠单抗（ROR = 15.7，95%置信区间：8.4 - 29.3）。针对IgE、T2细胞因子或T2细胞因子受体的单克隆抗体的寄生虫感染报告不成比例。虽然数据库中关于寄生虫感染的不良事件报告数量相对较少，但由此产生的安全信号不成比例，值得进一步调查。
