#4499 MATCHING-ADJUSTED INDIRECT COMPARISON OF SPARSENTAN VS DELAYED-RELEASE FORMULATION BUDESONIDE FOR PROTEINURIA REDUCTION IN ADULTS WITH IGA NEPHROPATHY

Abstract

Abstract Background and Aims Immunoglobulin A (IgA) nephropathy is a rare kidney disorder characterized by deposition of IgA in the glomeruli and associated with a reduction in renal function and increased risk of kidney failure [1,2]. In the absence of head-to-head trials, this study used matching-adjusted indirect comparison (MAIC)[3] of randomized control trial data to compare 9-month efficacy outcomes between potential treatment options for IgA nephropathy, sparsentan and recently FDA and EMA approved delayed-release formulation budesonide [4,5]. Method An unanchored MAIC was conducted using individual patient level data from the PROTECT trial for sparsentan and aggregate data from the NefIgArd trial for delayed-release formulation budesonide. Patients in the sparsentan arm of PROTECT were weighted to match the key baseline characteristics of patients in the budesonide delayed-release formulation arm of NefIgArd. After matching, the percentage reduction of urine protein-creatinine ratio (UPCR) at Month 9 relative to baseline were compared between sparsentan and delayed-release formulation budesonide. A two-tailed z-test was performed to estimate the p-value. Results Assessment of cross-trial heterogeneities suggested that PROTECT and NefIgArd trials were sufficiently similar in terms of patient population, key inclusion and exclusion criteria, and outcome definitions; however, due to differences in control arms (renin-angiotensin system blocker [RASB] optimization), an unanchored MAIC (comparing treatment arms directly) was selected. After matching, all matched baseline patient characteristics were well-balanced between corresponding treatment arms of the two trials. The comparative results showed that patients treated with sparsentan achieved a greater mean percentage reduction in UPCR at 9 months from baseline compared to budesonide-treated patients (p-value withheld pending FDA approval of sparsentan due to regulatory requirements). Conclusion The MAIC results showed that sparsentan was associated with a significantly larger percentage reduction in UPCR, a recognized surrogate of long-term kidney outcomes, from baseline to month 9 compared with delayed-release formulation budesonide.