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There is little data to inform use of renin angiotensin aldosterone system (RAAS) inhibitors in pediatric patients with systemic lupus erythematosus (SLE). Here, we sought to characterize RAAS inhibitor use in pediatric SLE and determine whether early RAAS inhibitor initiation among children with incident lupus nephritis is associated with decreased duration of chronic glucocorticoid exposure. A retrospective cohort study was performed of children (ages 5-18) with SLE and/or lupus nephritis in the Truven MarketScan™ Medicaid and Commercial databases (2013-2018) and estimated RAAS inhibitor use. Among incident nephritis cases, we used competing risk hazard models with inverse probability of treatment weighting to estimate the association between RAAS inhibitor initiation less than 180 days after diagnosis and time to glucocorticoid discontinuation with kidney failure as a competing event. Among 592 children with nephritis and 1407 children with non-kidney SLE, 67% and 15% ever received RAAS inhibitors, respectively. Median duration of RAAS inhibitor use among 323 incident users was 14 and 9 months in children with and without nephritis, respectively. Medicaid enrollment was independently associated with greater likelihood of RAAS inhibitor use, irrespective of nephritis. Among 158 incident nephritis cases, early RAAS inhibitor initiation was significantly associated with a faster rate of glucocorticoid discontinuation (adjusted sub-distribution hazard ratio 1.81, 95% confidence interval [1.09 - 3.00]). Thus, early initiation of RAAS inhibitors may have a role in children newly diagnosed with lupus nephritis; not only those with refractory proteinuria after induction therapy. Hence, integrated health systems data could be leveraged to confirm these findings and optimize adjunctive therapies in pediatric lupus.

Using a representative sample of children with systemic lupus erythematosus (SLE) in the United States, we characterized prescription claim-based hydroxychloroquine and immunosuppressant adherence estimates and evaluated their concurrent and predictive validity.We identified children ages 5-18 with SLE in the Truven Health MarketScan® Commercial and Medicaid claims databases (2013-2018). Among new users of hydroxychloroquine and immunosuppressant medications, we calculated proportion of days covered (PDC) over 365 days to estimate adherence by user group (mycophenolate, azathioprine, methotrexate, and any immunosuppressant use). Agreement between adherence estimates was evaluated with intraclass correlation coefficients (ICC) and kappa statistics. Separate negative binomial regression models were used to estimate associations between (a) hydroxychloroquine, (b) immunosuppressant, or (c) concurrent immunosuppressant/hydroxychloroquine non-adherence and subsequent hospitalizations, adjusted for baseline demographics, disease severity, and healthcare utilization.Among 423 new hydroxychloroquine/immunosuppressant users, 63% were Medicaid recipients. Sufficient adherence (PDC≥80%) ranged from 33 to 45% for immunosuppressants vs. 51-52% for hydroxychloroquine. Agreement between hydroxychloroquine and immunosuppressant adherence was modest overall, but better for mycophenolate (ICC 0.55) than methotrexate (0.27). Hydroxychloroquine non-adherence was associated with a 2.9-fold higher incidence of subsequent hospitalizations (95% CI [1.2-7.1]), whereas immunosuppressant and concurrent non-adherence were associated with 5.9 [2.4-14.6] and 5.6-fold [2.0-15.5] increased incidence, respectively. Use of concurrent adherence improved upon estimation of hospitalization risk compared to hydroxychloroquine adherence, but not immunosuppressant adherence alone.Hydroxychloroquine adherence is an imperfect proxy for adherence to other lupus medications among children with SLE, and therefore assessing immunosuppressant adherence concurrently adds value to hydroxychloroquine adherence assessments. Prescription claims-based immunosuppressant adherence measures are predictive of acute care utilization and may inform population management strategies.