Use of renin angiotensin aldosterone system inhibitors in children with lupus and time to glucocorticoid discontinuation

Abstract

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.

Keywords: angiotensin-converting enzyme inhibitors; glomerulonephritis; pediatric nephrology; renin-angiotensin system; systemic lupus erythematosus.