(X) Association Between Antihistamine Exposure and Newly Diagnosed Juvenile Idiopathic Arthritis: A Nationwide Analysis

Publication Number: 1022

Background: Antibiotic exposure has been linked to incident juvenile idiopathic arthritis (JIA) through a purported mechanism of microbiome disruption. Among non-sedating H1 antagonists, loratadine, but not cetirizine, has direct antibacterial properties and may disrupt microbiota.

Objectives: To test if loratadine exposure is associated with newly diagnosed JIA.

Methods: We performed a nested case-control study using data from 45-state US Medicaid claims data (2001-2012). Cases were newly diagnosed with JIA based on previously validated diagnostic algorithms. Each case was matched to up to 10 randomly selected unaffected controls by age, sex, state, and years of enrollment at the time of JIA diagnosis (index date). Subjects were excluded for non-JIA rheumatic diseases, immunodeficiencies, malignancy, prior immunosuppression, and exposure to multiple antihistamines. Loratadine and cetirizine exposure was defined by a prescription dispensed prior to a 3-month pre-index lag period and categorized by number of courses dispensed and time relative to the index date. The association between antihistamine exposure and incident JIA diagnosis was estimated using conditional logistic regression, adjusting for race, eligibility type, allergic and other comorbid conditions, antibiotics, and prior infections, and expressed as odds ratios (ORs) with 95% confidence intervals (CIs). To approximate an active-comparator study, exposed groups were compared indirectly based on the difference of respective coefficients.

Results: We included 13,012 cases with JIA and 128,996 controls. 16,728 subjects were exposed only to loratadine, 10,369 only to cetirizine, and 105,851 were unexposed to antihistamines. Compared to no antihistamine exposure, we found weak associations for loratadine exposure (OR 1.17 [95% CI 1.11, 1.25]) and cetirizine exposure (OR 1.13 [95% CI 1.05, 1.22]). However, loratadine was not associated with JIA when compared to cetirizine (OR 1.04 [95% CI 0.95, 1.13]). Further, we found a weak association for a single course of loratadine within the past year (OR 1.15 [95% CI 1.01, 1.32]) but not 2+ courses (OR 0.96 [95% CI 0.80, 1.15]). A possible but not significant dose-response relationship was observed for cetirizine (single course, OR 1.07 [95% CI 0.88, 1.29]; 2+ courses, OR 1.19 [95% CI 0.95, 1.48]). The timing of loratadine exposure was also not associated with JIA diagnosis (within past year versus 1-2 years prior, OR 1.09 [95% CI 0.89, 1.33]).

Conclusions: Both loratadine exposure and cetirizine exposure were weakly associated with JIA relative to no antihistamine exposure, but no difference was found between loratadine and cetirizine exposure, with repeated loratadine courses, or with timing of loratadine exposure, arguing against a causal association.