Efficacy and Safety of a Targeted-Release Formulation of Budesonide in Patients with IgAN and Severe Renal Impairment: A Real-World Study

Background: The targeted-release formulation of budesonide (Nefecon), which specifically targets gut-associated lymphoid tissue to reduce galactose-deficient IgA1 production, has been shown to significantly decrease proteinuria and stabilize renal function in patients with IgA nephropathy (IgAN) who have mild to moderate renal impairment. However, there is limited clinical evidence regarding its efficacy and safety in IgAN patients with severe renal impairment. Methods: This single-center retrospective study included patients with primary IgAN and persistent proteinuria (UPCR ≥ 0.8 mg/mg or 24-hour proteinuria ≥ 1 g/d) despite supportive therapy and with eGFR ≤ 35 ml/min/1.73 m2. The primary endpoints were changes in UPCR, UACR, and urinary RBC count. Secondary efficacy outcomes included changes in eGFR and the assessment of adverse events. Results: 26 eligible patients with IgAN were treated with Nefecon. After 12 weeks of treatment, the UPCR decreased from 1.87mg/mg (IQR 1.12-2.89) to 0.70 mg/mg (0.39-1.23) (P < 0.001), resulting in a median reduction of -56.09% (IQR -77.92 to -36.80). The UACR reduced from 1.42 mg/mg (0.83-2.25) to 0.44 mg/mg (0.22-1.04) (P < 0.001), with a median reduction of -65.85% (-90.24 to -41.80). The urinary RBC count decreased from 40.3 cells/μl (15.5-124.7) to 11.6 cells/μl (4.9-27.5) (P < 0.001), showing a median reduction of -66.07% (-84.41 to -26.61). The eGFR increased from 21.31 ± 8.85 ml/min/1.73 m2 to 26.00 ± 11.40 ml/min/1.73 m2 (P = 0.008), with a median increase of 14.62% (IQR -3.53 to 48.15). Throughout the treatment period, no serious adverse events were observed. Conclusion: Nefecon, when administered to IgAN patients with severe renal impairment and persistent proteinuria, was well-tolerated and resulted in a significant reduction in both proteinuria and hematuria, along with an improvement in eGFR. Funding: Government Support – Non-U.S.Changes in (a, b) UPCR, (c, d) UACR, (e, f) urinary RBC count, and (g, h) eGFR during treatment with Nefecon.