#368 Matching-Adjusted Indirect Comparisons of eGFR slopes in the PROTECT study with UK RaDaR IgA nephropathy population and the control arm of NefIgArd

Abstract

Abstract Background and Aims Immunoglobulin A nephropathy (IgAN) is a rare kidney disorder characterized by deposition of IgA in the glomeruli leading to an increased risk of kidney failure. The PROTECT clinical trial in IgAN was designed to determine the long-term (approximately 2 year) nephroprotective potential of treatment with sparsentan compared to a blinded active control angiotensin receptor blocker (ARB) irbesartan, titrated to the maximum labelled dose after randomization (achieved in 97% of patients). To understand PROTECT clinical trial results relative to delivery of standard of care (SoC) treatment for IgAN in other clinical settings, this study compared two-year eGFR total slope outcomes between the two arms of PROTECT and delivery of SoC in two populations applying similar eligibility criteria: Method Using individual patient data (IPD) from PROTECT, unanchored matching-adjusted indirect comparisons (MAICs) were performed. Patients in both arms of PROTECT were weighted to match key baseline characteristics of the two comparator populations. Matching was based on published clinical characteristics using the method of moments. After weighting, two-year eGFR total slopes were calculated using random coefficients models. Two-tailed z-tests with pooled standard errors were used for indirect comparison. Results Based on assessment of cross-data source characteristics, populations were found to be sufficiently comparable for unanchored MAIC. After weighting IPD from PROTECT, all matched baseline patient characteristics were well-balanced between data sources. Comparative results showed that patients treated with maximally titrated irbesartan or sparsentan in PROTECT exhibited a slower decline in kidney function compared to SoC delivered in a real-world setting (RaDaR), with differences of: Similar results were observed compared to SoC delivered in a clinical trial (NefIgArd), with differences of: Conclusion Both “maximally tolerated dose of ARB” (as recommended in the KDIGO guideline for IgAN) using irbesartan in PROTECT and sparsentan were associated with significantly slower decline in kidney function compared to real-world SoC treatment for IgAN (RaDaR) and delivery of physician defined, optimized SoC (& placebo) in the context of a clinical trial (NefIgArd). 2-year eGFR slope differences between clinical trials in IgAN need to be considered in the context of what is achieved in current clinical practice. With existing real-world and emerging clinical trial data in IgAN, MAIC is an approach that can be applied to compare outcomes between relevant, sufficiently aligned data sources.