Abstract
BACKGROUND: Mas-related G protein-couple receptor x2 (Mrgprx2) activation underlies many common non-IgE-mediated adverse drug reactions (ADRs), yet the features of patients with reactions to Mrgprx2-activating drugs are unknown. OBJECTIVE: To characterize the patient-specific comorbidities and laboratory characteristics associated with listed reactions to Mrgprx2-activating drugs, including fluoroquinolones, morphine, neuromuscular blockade agents, vancomycin, and leuprolide. METHODS: We used a retrospective, observational cohort study design using electronic health record data from adults with an Mrgprx2-activating drug exposure recorded within a hospital system clinical Biobank. Odds ratios (ORs) and incidence rate ratios for clinical characteristics associated with ADRs, including immediate hypersensitivity reactions, were calculated using multivariable logistic regression. RESULTS: Among 59,763 patients exposed to Mrgprx2-activating drugs, 4846 had a listed ADR. Female sex, White race, asthma (OR: 1.81, 95% confidence interval [CI]: 1.68-1.94), chronic urticaria (OR: 1.73, 95% CI: 1.46-2.05), and mastocytosis (OR: 12.79, 95% CI: 5.98-27.02) were associated with increased odds of a reaction. Overall, patients with allergic disease had 1.21 times the rate of an ADR compared with patients without allergic disease. Elevated absolute eosinophil count was inversely associated with reactions, and there was no association with elevated total IgE. Observed associations were similar in a patient subgroup with immediate-type hypersensitivity reactions. CONCLUSION: Specific allergic diseases and common allergic biomarkers are differentially associated with ADRs to Mrgprx2-activating drugs. These findings from a large, "real world" drug-exposed population highlight clinical factors that may contribute to non-IgE-mediated drug allergy.