OBJECTIVE: We linked pharmacy dispensing data to clinical data in the electronic health record (EHR) to (1) identify characteristics associated with adherence to methotrexate (MTX) and (2) determine the association between adherence and disease activity in patients with juvenile idiopathic arthritis (JIA). METHODS: We conducted a single-center retrospective cohort study of incident MTX recipients with JIA treated between January 2016 and September 2023 for ≥12 months. Using pharmacy dispensing data, complemented by EHR data, we estimated adherence using medication possession ratios (MPRs) over the first 365 days of treatment. We used Fisher's exact and Wilcoxon rank-sum tests to compare patient characteristics between adherent (MPR ≥80%) and nonadherent (MPR <
80%) groups and multivariable linear regression to investigate associations between MPR and active joint count. RESULTS: Among 224 patients, 81 (36.2%) were classified as nonadherent. In bivariate analysis, patients of younger age, of Black race, and from areas with lower child opportunity index were more likely to be classified as nonadherent. In multivariable analysis, active joint count changed from baseline to 12-month follow-up by -0.38 joints in the adherent compared to nonadherent group (95% confidence interval [CI] -0.74 to -0.01) and by -1.18 joints in patients with polyarticular course (95% CI -2.23 to -0.13). CONCLUSION: Linking dispense data to clinical EHR data offers a novel, objective method for evaluating adherence to chronic medications. We identified demographic and area-level determinants of adherence, along with small but statistically significant differences in JIA disease activity measures by adherence status. Future work is needed to evaluate adherence as a potential mediator of known outcome disparities for socially disadvantaged populations.