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)

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.

FIGURE 1

Overview of the data extraction process.

FIGURE 2

Reported health outcomes for benralizumab, dupilumab, mepolizumab, and omalizumab, expressed in absolute numbers and proportions per drug.

FIGURE 3

Signals of disproportionate reporting for biologics of interest compared to other drugs concerning parasitic infections. Results are shown of the primary analysis utilizing the entire database and of the 1st secondary analysis. No signal could be produced for reslizumab due to lack of power. † Results from the 1st secondary analysis utilizing the entire database, excluding drugs under Anatomical Therapeutic Chemical classification group Antiparasitic products, insecticides and repellents [see methods for detailed description]. ATC, Anatomical Therapeutical Chemical classification; CI, Confidence Interval; ROR, Reporting Odds Ratio.

FIGURE 4

Signals of disproportionate reporting within the group of biologics of interest concerning parasitic infections. Results are shown of the 2nd secondary analysis utilizing reports only from dupilumab, omalizumab, mepolizumab, benralizumab, and reslizumab [see methods for detailed description]. No signal could be produced for reslizumab due to lack of power panel. ATC, Anatomical Therapeutical Chemical classification; CI, Confidence Interval; ROR, Reporting Odds Ratio.