Reshaping the therapeutic landscape of IgA nephropathy: a Bayesian network meta-analysis on the comparative efficacy and safety of immunosuppressants and targeted agents.

backgroundComparative evidence between conventional immunosuppressants and emerging targeted therapies for IgA nephropathy (IgAN) is limited by a lack of head-to-head trials. We conducted a Bayesian network meta-analysis to compare efficacy and safety signals across available randomized evidence.

methodsPubMed, the Cochrane Library, Web of Science, Scopus, and Embase were searched from inception to March 2025 for randomized controlled trials in adults with biopsy-proven IgAN comparing methylprednisolone, mycophenolate mofetil (MMF), tacrolimus, targeted-release budesonide (Nefecon), iptacopan, or sibeprenlimab versus placebo or supportive care. Outcomes included serious adverse events (SAEs), estimated glomerular filtration rate (eGFR) slope, proteinuria, and urinary protein-to-creatinine ratio (UPCR). Bayesian random-effects models generated risk ratios or mean differences with 95% credible intervals, and surface under the cumulative ranking (SUCRA) probabilities were used to describe comparative rankings. Prespecified subgroup analyses by baseline eGFR (< 60 vs. ≥ 60 mL/min/1.73 m²) were assessed using interaction tests.

resultsSeventeen trials were included. For SAEs, most comparisons were inconclusive because of sparse data and wide uncertainty intervals, although iptacopan showed a numerically lower point estimate for serious adverse events within the network. Subgroup analyses did not suggest effect modification by baseline eGFR. For kidney function, Nefecon showed the most favorable point estimate for eGFR slope, ranking highest in SUCRA analyses; however, credible intervals crossed the null and these rankings should be interpreted with caution given the sparse evidence network. For proteinuria outcomes, methylprednisolone showed the largest reductions versus placebo when assessed by UPCR, while iptacopan and sibeprenlimab were also associated with reductions; many between-treatment contrasts remained imprecise.

conclusionsAmong evaluated therapies, Nefecon showed the most favorable point estimate for eGFR slope; however, this finding was imprecise and should be interpreted as hypothesis-generating rather than evidence of superiority. Overall, comparative estimates remain uncertain because of sparse networks, heterogeneous regimens, and limited follow-up. SUCRA rankings should be considered exploratory rather than evidence of treatment superiority. These findings support individualized treatment decisions and highlight the need for larger, longer-term, directly comparative trials with hard renal outcomes.