OPEN LABEL, SINGLE ARM, MULTICENTER, PROSPECTIVE STUDY ON ORAL ENTERIC COATED BUDESONIDE THERAPY FOR PRIMARY IGA NEPHROPATHY

Introduction:

In recent years, targeted release Budesonide has become the sheet anchor of therapy in the management of IgA nephropathy.  In India only an enteric coated formulation (Iganef 9 mg) is available which is also more economical than the target release preparation.  This study was conducted to investigate its efficacy on proteinuria reduction and eGFR stabilization in biopsy proven patients with IgA Nephropathy.

Methods:

All biopsy proven patients with IgA Nephropathy who were on maximally tolerated ACEinhibitors/ARB doses for at least 3 months and having proteinuria (urine albumin creatinine ratio) UACR >300 mg/g creatinine (≥ A3) were prospectively evaluated between Jan 2023 to June 2024 in 6 centers from different parts of India.  We included all patients irrespective of eGFR, who were not currently on any renal replacement therapy. Iganef was initiated at 9 mg orally twice daily for 9 months.  The primary outcome was percentage UACR reduction at 3-m, 6-m and 9-m of initiation of therapy. The secondary outcome was eGFR stabilization at follow-up.

Results:

Of 242 patients receiving Iganef treatment, 182 were included in the analysis. The median (IQR) age of the cohort was 34.2(28-42) years, with 104(57.1%) male population. The baseline blood pressure at the time of Iganef initiation [systolic = 127(120-136) and diastolic = 81(75-88) mmHg].  The baseline UACR was 1792(IQR = 1058-2607; range = 303-10,000) mg/g creatinine.  The distribution of proteinuria was as follows : <1000 [37(20.3%)] mg ,1000 to 3000 mg [102(56%)] and > 3000 mg proteinuria [43(23.6%)].  The baseline serum creatinine was 1.43(1.02 -2.12) mg/dl. The baseline eGFR calculated by CKD-EPI 2021 equation was 46.25(32.1-72.9) ml/min/1.73m2, with KDIGO eGFR staging as G5, G4, G3b, G3a, G2, and G1 in 5(2.7%), 33(18.1%),48(26.3%), 27(14.8%), 36(19.7%), and 33(18.1%) patients respectively. The percentage proteinuria reduction from baseline at 3 m, 6 m and 9 m follow-up was 36.22(16.9 - 61.13) 52.17(39.4-71.2) 69(56.6-79) % with linear correlation (R2 = 0.99) within follow-up period. There was lesser % UACR reduction with baseline UACR < 1000 mg/g compared to above 1000 mg/g at 3m [33.42±43.3 vs 36.5±33.1; p-value = 0.6807],  6-m [40.4±44.3 vs 50.4±39.5;p-value =  0.1907] and 9-m[   38±58.6 vs 66.3±20.8);p-value =0.0018]. MEST-C staging (n = 103), where M1, E1, S1, T1 and C1/ C2 was classified in   59(79.5%), 20(19.4%), 73(70.8%), 32(31%), 12/2(13.5%) patients. MEST -C correlation with % UACR reduction with baseline eGFR is shown in Figure 1. In our cohort, with baseline eGFR is below 40 ml/min/1.73m2, the % U-ACR reduction is similar irrespective of MEST-C staging. When baseline eGFR is above 60 ml/min/1.73 m2, the %UACR reduction does not correlate with E, S, and T score. However, M 0 and C0 has higher %UACR reduction when baseline eGFR is above 60 ml/min/1.73m2The eGFR stabilized with a slight improvement at 3-m[ 0(-12 to 6)], 6-m [5(-2.9 to 11.1)], and 9-m 5.6(0 to 14.5) ml/min. Additionally, we compared proteinuria reduction in patients with baseline UACR < 800mg/g (n=27 )  creatinine vs > 800 mg/g (n=155) creatinine. At 9 months of therapy %UACR reduction was similar 52.6 and 56.1 respectively.  On subgroup analysis, patients with baseline eGFR (in ml/min/1.73m2) < 35 (n=55) had lower eGFR improvement (1.76 vs 9.36) compared to patients with baseline  eGFR > 35  (n=127). There were no serious adverse events resulting requiring hospitalization or drug discontinuation.

Conclusions:

This is the largest real world study till date in IgA nephropathy patients which demonstrates  a significant reduction in proteinuria in the cohort with the extended release budesonide (Iganef) with eGFR stabilization at 9 months of therapy. In our study Iganef was beneficial even in pateints with lower grades of proteinuria  (<800 mg/g)  and advanced stages of CKD ( eGFR <35) which were not evaluated in Nefgan trial.  However, a longer follow-up study is needed to confirm its sustained benefit beyond completion of nine months of therapy on both proteinuria reduction and eGFR stabilization. Additionally, Iganef has a promising safety profile, with no serious hospitalizations for infections being reported in our cohort.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.