(SLC-026) Association between antibiotic exposure and response to treatment of juvenile idiopathic arthritis

Background: Juvenile idiopathic arthritis (JIA), the most common pediatric rheumatic disease, has been tied to microbiome disruption (dysbiosis). Dysbiosis in adults with arthritis affects response to methotrexate, a common disease-modifying antirheumatic drug (DMARD), but the effects of microbiome-altering drugs (e.g., antibiotics) on methotrexate response for JIA are unknown.

Objectives: To test if antibiotic exposure is associated with response to methotrexate for JIA, hypothesizing shorter times to treatment change after antibiotic exposure and larger effects with more recent, frequent, and disruptive exposures.

Methods: We conducted a retrospective cohort study using national US public insurance administrative claims data (2001-2019). We included children ages 1-17 diagnosed with JIA who were initiating methotrexate monotherapy or, for comparison, tumor necrosis factor inhibitor (TNFi) monotherapy, after ≥10 months of continuous enrollment without DMARDs (baseline period). Antibiotic exposure during the baseline period was assessed and characterized by timing, number of courses, and type. Nonbacterial antimicrobial drugs were evaluated as a negative control exposure. As a proxy of treatment ineffectiveness, the primary outcome was initiation of a second DMARD after at least 1 month, a lag representing hypothetical induction time between antibiotic-induced dysbiosis and altered DMARD response. Censoring occurred with a 60-day gap in DMARDs, completion of 10 months of follow-up, loss of enrollment, or death. Associations between antibiotic exposure and treatment change were estimated using Cox regression, adjusting for demographic, disease, treatment, and health utilization covariates, and represented by adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs).

Results: We identified 5510 new methotrexate users (mean age 9.5±4.9 years, 68.6% female, 55.4% exposed, 16.1% with outcomes) and 1274 new TNFi users (mean age 11.6±4.5 years, 61.9% female, 50.2% exposed, 15.6% with outcomes). No relationship was observed between baseline antibiotic exposure and treatment change in methotrexate users (aHR 0.99, 95% CI 0.86, 1.13) or TNFi users (aHR 1.19, 95% CI 0.83, 1.52). Timing, number of courses, and type of antibiotic exposure, as well as nonbacterial antimicrobial drug exposure, were also not associated with treatment changes in methotrexate or TNFi users.

Conclusions: Antibiotic exposure is not associated with changes in DMARD treatment in children with JIA, suggesting that dysbiosis does not play a major role in response to methotrexate or TNFi for JIA.