Efficacy and safety of belimumab in IgA nephropathy: real-world evidence

Belimumab, a monoclonal antibody targeting B lymphocyte stimulator, has shown benefits in systemic lupus erythematosus and lupus nephritis, but its role in IgA nephropathy (IgAN) remains unclear. We evaluated the effectiveness and safety of belimumab in IgAN.

This retrospective cohort study included biopsy-proven IgAN patients at Tongji Hospital, China (July 2020-June 2024). 69 patients treated with belimumab were compared with 137 propensity score-matched controls receiving standard therapy. The primary outcome was proteinuria remission, defined as a reduction in 24-hour urinary protein excretion or urine protein-to-creatinine ratio (UPCR) to < 50% of baseline.

Among 206 patients with IgAN (median age 37 years, baseline eGFR 79 ml/min/1.73 m², proteinuria 1.1 g/24 h), 173 (84%) achieved proteinuria remission within 12 months. Remission was higher in the belimumab group: 59% vs 46% at 3 months, 77% vs 66% at 6 months, and 93% vs 80% at 12 months (P = 0.025 at 12 months), with lower time-averaged UPCR at 6 months [371 (248 738) vs.463(262 855) mg/g] and 12 months [360 (234 560) vs.433(243 720) mg/g, P = 0.066]. In newly diagnosed patients, remission was significantly higher at 3 months (76.5% vs. 47.1%, P = 0.009) and 6 months (88.2% vs. 67.6%, P = 0.045), with similar trends at later time points. In patients with baseline UPCR >600 mg/g and those receiving RAAS inhibitors, belimumab demonstrated comparable or superior proteinuria reduction. No excess of common adverse events was observed in the belimumab group.

Belimumab treatment was associated with higher proteinuria remission rates in patients with IgAN, without an increased incidence of common adverse events. These findings suggest that belimumab may represent a superior therapeutic approach for IgAN in real-world clinical practice.