A second course of budesonide had additional positive effects on proteinuria and kidney function in previously treated patients with immunoglobulin A nephropathy
Presenter: Richard A. Lafayette, MD, Stanford University, Stanford, CA
In patient with immunoglobulin A nephropathy previously treated with budesonide, a second 9-month treatment course had an additional positive effect on proteinuria and kidney function, according to this open-label extension study.
In adult patients with primary immunoglobulin A nephropathy (IgAN) at risk of disease progression, a second 9-month course of treatment with budesonide had positive effects on proteinuria and kidney function decline, according to results from this open-label 9-month extension study of the NeflgArd trial presented at Kidney Week 2024.
Budesonide, a novel, oral, targeted-release formulation (Tarpeyo, formerly Nefecon), had similar effects on proteinuria and kidney function as the double-blind treatment regimen, according to lead author Richard A. Lafayette, MD, Stanford University, Stanford, CA.
Budesonide was first approved by the US Food and Drug Administration in December 2021 based on proteinuria reductions in the phase 3 NeflgArd study. In December of 2023, it became the first fully FDA-approved treatment for IgAN based on estimated glomerular filtration rate (eGFR) improvements found in NeflgArd at 2 years (Lafayette. Lancet 2023;402:859).
In the NeflgArd trial, budesonide (Nefecon) treatment at 16 mg/d for 9 months led to a statistically significant benefit in time-weighted average eGFR and a durable proteinuria reduction compared with placebo. In this data presentation, Dr. Lafayette reported on the effect of budesonide in patients who completed the NeflgArd trial open-label extension.
This phase 3b open-label extension of NeflgArd enrolled 119 patients: 45 [38%] were budesonide experienced and 74 [62%] were budesonide naive. All participants had completed the initial 9-month double-blind trial and had persistent proteinuria of at least 1 g/d or a urine protein-creatinine ratio (UPCR) of at least 0.8 g/g and an eGFR of at least 30 mL/min/1.73 m2 despite optimized renin-angiotensin system blockade.
Patients who completed a full 9-month course of budesonide without dose reductions were included in the extension trial. All participants (79% male, 84% White) received budesonide for 9 months (plus 2 weeks of tapering at 8 mg/d). The primary efficacy endpoints were ratios of eGFR and UPCR at 9 months versus the open-label extension baseline values.
The median eGFR at the open-label extension baseline was 50.4 and 49.2 mL/min/1.73 m2, respectively, for budesonide-experienced versus budesonide-naive participants, with median UPCR at 1.28 and 1.37 g/g, respectively.
For all 119 pts, the overall UPCR reduction from baseline to 9 months was 32%, with an absolute eGFR decline of 1.43 mL/min/1.73 m2. After 9 months of open-label treatment, similar UPCR reductions and eGFR changes were observed in both the budesonide-experienced and budesonide-naive groups. Generally, Dr. Lafayette said, treatment was well tolerated.
He concluded, “These study findings provide valuable insights into the efficacy and safety of additional treatment with Nefecon and demonstrate that, in previously treated patients, a second 9-month course had an effect on proteinuria and kidney function decline similar to a first treatment course, without additional safety concerns.”