Parasitic infections related to anti-type 2 immunity monoclonal antibodies: a disproportionality analysis in the food and drug administration's adverse event reporting system (FAERS)

Front Pharmacol. 2023 Nov 14:14:1276340. doi: 10.3389/fphar.2023.1276340. eCollection 2023.

Abstract

Introduction: 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. Methods: 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). Results: 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). Conclusion: 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.

Keywords: FAERS; biologicals; disproportionality analysis; helminth infections; monoclonal antibodies; parasitic infections; pharmacovigilance; spontaneous reporting.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work has received support from the European Health Data and Evidence Network (EHDEN) project. EHDEN has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No. 806968. SR is funded through the Health, innovation and research institute at Ghent University Hospital (HIRUZ), grant FIKO21/TYPE2/033.