Budesonside improves urinary protein to creatinine ratio (UPCR) and maintains estimated glomerular filtration rate (eGFR) in adult patients with IgA nephropathy (IgAN), according to interim results from a phase 3 trial.
In Part A of the double-blind NefIgArd trial (ClinicalTrials.gov: NCT03643965), investigators randomly assigned 199 patients with IgAN and persistent proteinuria despite stable, optimized renin angiotensin system blockade to budesonide (16 mg/d) or placebo for 9 months. At baseline, median UPCR was 1.26 g/g and median proteinuria was 2.26 g/24 hours (58% had proteinuria of 2 g or more in 24 hours). Median eGFR was 55 mL/min/1.73 m2.
The budesonide formulation was Nefecon, a corticosteroid that is hypothesized to target mucosal B-cells in the ileum, including the Peyer’s patches, which are responsible for the production of galactose-deficient IgA1 antibodies (Gd-Ag1) causing IgAN.
At 9 and 12 months, 24-hour UPCR was a significant 27% and 48% lower, respectively, in the budesonide vs placebo group, Brad H. Rovin, MD, of Ohio State University Wexner Medical Center in Columbus, Ohio, and colleagues reported in Kidney International. In addition, eGFR at 9 months was preserved in the budesonide group with a decrease from baseline of 0.17 vs 4.04 mL/min/1.73 m2 in the placebo group.
Treatment-emergent adverse events (TEAEs) occurred in 86.6% of the budesonide group and 73.0% of the placebo group. Most TEAEs were mild to moderate (1% severe) and reversible, the investigators reported. The most common TEAEs in the budesonide group were hypertension, peripheral edema, muscle spasms, and acne. Infection occurred in 39.2% of the budesonide and 41.0% of the placebo group. None of the patients experienced severe infections requiring hospitalization. Treatment discontinuation occurred in 9.3% of the budesonide group and 1.0% of the placebo group.
“This is the first phase 3 RCT to show treatment benefits of this magnitude with a drug that we postulate may target the underlying pathophysiology of IgAN,” Dr Rovin’s team wrote. Results from Part B of the trial are expected in 2023 and will inform FDA approval.
Disclosure: This research was supported by Calliditas Therapeutics AB. Please see the original reference for a full list of disclosures.
Barratt J, Lafayette R, Kristensen J, et al. Results from part A of the multi-center, double-blind, randomized, placebo-controlled NefIgArd trial evaluated targeted-release formulation of budesonide for the treatment of primary immunoglobulin A nephropathy. Kidney Int. Published online October 18, 2022. doi:10.1016/j.kint.2022.09.017