Real-world multicenter evidence on Nefecon for attenuating proteinuria and kidney function decline in IgA nephropathy

Targeted-release budesonide (Nefecon) has demonstrated efficacy in IgA nephropathy (IgAN) trials, yet real-world data across disease severity spectrum remains limited.

This multicenter, retrospective cohort study included 148 biopsy-proven IgAN adults (Nefecon =79; RASi =69). Primary endpoints were 9-month changes in proteinuria and eGFR. Mahalanobis distance matching within propensity score calipers addressed baseline imbalances. Response dynamics and safety were secondarily evaluated.

Despite worse baseline eGFR (median 54.2 vs. 85.3 mL/min/1.73m²; P < 0.001) and more severe pathological lesions in the Nefecon group compared to RASi group, Nefecon was associated with greater proteinuria reduction (-1.25 vs. -0.58 g/24h; P < 0.001) and favorable eGFR trajectories (+2.7 vs. -11.2 mL/min/1.73m²; between-group difference 13.9 mL/min/1.73m²; 95% CI 12.7 to 15.1; P <0.001), findings remained largely consistent after Mahalanobis distance matching adjustment. Complete and partial remission rates were higher (29.1% and 54.2% vs. 10.1% and 23.2%; P < 0.001), with 59.5% achieving ≥50% proteinuria reduction versus 21.7% (RR 2.70, 95% CI 1.62-4.51). Treatment effects varied by baseline disease severity. Enhanced antiproteinuric efficacy was observed in patients with proteinuria >1.5 g/24h (interaction P = 0.003), while kidney function preservation was most pronounced in those with eGFR <60 mL/min/1.73m². Notably, 51.1% of initial non-responders achieved remission by 9 months, with complete remission rates increasing 4.6-fold over time. Adverse events were consistent with corticosteroid exposure; menstrual disturbance occurred in 39.5% of females. Serious adverse events were rare (2.5%).

This real-world observational analysis shows Nefecon associated with improved proteinuria and eGFR outcomes across IgAN severity, extending randomized trial evidence to patients with advanced CKD and revealing substantial delayed response.