Matching-adjusted indirect comparison of kidney function in patients with immunoglobulin A nephropathy treated with nefecon or sparsentan

Aim: We compared the effects of nefecon, an oral targeted-release budesonide formulation, and sparsentan, an oral, dual endothelin-angiotensin receptor antagonist, on estimated glomerular filtration rate (eGFR) in patients with immunoglobulin A nephropathy, a leading cause of chronic kidney disease. Materials & methods: We conducted an anchored matching-adjusted indirect comparison (MAIC) using patient-level data from NefIgArd ( NCT03643965 ; n = 364), a randomized (1:1) trial of nefecon plus optimized renin–angiotensin system inhibitor (RASi) therapy versus placebo plus RASi; and aggregate data from PROTECT ( NCT03762850 ; n = 404), a randomized (1:1) trial of sparsentan versus irbesartan, an angiotensin receptor blocker. Mean absolute eGFR change and mean relative urine protein-to-creatinine and urine albumin-to-creatinine ratio changes from baseline at 9, 12 and 24 months (NefIgArd) or 36, 48 and 106 weeks (PROTECT) were analyzed using a mixed-effects model for repeated measures. A composite outcome (time to confirmed 40% eGFR reduction, end-stage kidney disease or all-cause mortality) was also included. An unanchored MAIC and network meta-analysis were used as sensitivity analyses. Results: The matching process reduced the effective sample for the NefIgArd trial from 364 to 208. Absolute eGFR change significantly favored nefecon over sparsentan at 9 months (mean difference, ml/min/1.73 m 2 [95% credible interval]: 5.7 [3.1–8.2]), 12 months (3.5 [1.0–6.0]) and 24 months (3.3 [0.0–6.5]). Differences in other outcomes were generally not statistically significant. Sensitivity analysis results were consistent with the main findings. Conclusion: In patients with immunoglobulin A nephropathy, nefecon plus optimized RASi may preserve kidney function to a greater extent than sparsentan.