Recent antibiotic exposure and response to treatment of juvenile idiopathic arthritis: a retrospective cohort study.

Abstract

Background: Juvenile idiopathic arthritis (JIA) has been tied to microbiome disruption and antibiotic exposure. Gut microbiota may affect how adults with rheumatoid arthritis respond to methotrexate. We tested if exposure to antibiotics was associated with response to methotrexate for JIA.

Methods: We conducted a retrospective cohort study using national US public and private insurance claims data (2001-2023). We included children ages 1-17 continuously enrolled for ≥ 10 months and diagnosed with JIA who initiated methotrexate monotherapy or, for comparison, tumor necrosis factor inhibitor (TNFi) monotherapy without prior disease-modifying antirheumatic drug (DMARD) exposure. Antibiotic exposure during the 10-month baseline period was characterized by number of courses, timing, and type. The primary outcome was initiation of a second DMARD after ≥ 30 days (proxy of treatment ineffectiveness). Associations between antibiotic exposure and treatment change were estimated using Cox regression, adjusting for database and baseline demographic, disease, treatment, and health utilization covariates, and represented by adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). In additional analyses, we examined differences based on JIA category (juvenile spondyloarthritis vs. others), outcome specification, and follow-up starting up to 90 days after initial DMARD exposure.

Results: We identified 6,135 new methotrexate users (54.4% antibiotic-exposed) and 1,554 new TNFi users (49.5% antibiotic-exposed), among whom approximately 20% experienced the primary outcome over 10 months of follow-up. No relationships were observed between pre-DMARD antibiotic exposure and DMARD changes in methotrexate users (aHR 1.01, 95% CI 0.90, 1.13) or TNFi users (aHR 1.10, 95% CI 0.86, 1.40). Number of antibiotic courses, antibiotic timing, and type of antibiotic exposure, as well as nonbacterial antimicrobial drug exposure, were also not associated with treatment changes in methotrexate or TNFi users. Findings based on JIA category, alternative outcome definitions, and delayed start of follow-up were consistent.

Conclusions: Recent antibiotic exposure is not associated with changes in DMARD treatment in children with JIA. This finding is reassuring for a population with higher risks for serious infections than other children and with high rates of antibiotic exposure.