Comparative Evidence for IgA Nephropathy Therapies in a Network Meta-Analysis

Key Takeaways

• Nefecon was associated with the most favorable eGFR slope point estimate and the highest SUCRA ranking, although uncertainty remained.
• Methylprednisolone showed the largest UPCR reductions versus placebo, while iptacopan and sibeprenlimab were also associated with proteinuria reductions.
• Serious adverse event comparisons were mostly inconclusive because the network was sparse and intervals were wide, and SUCRA rankings were treated as exploratory.

A Bayesian network meta-analysis of 17 randomized trials in adults with biopsy-proven IgA nephropathy compared conventional immunosuppressants with newer targeted agents across efficacy and safety outcomes. For kidney function, targeted-release budesonide (Nefecon) had the most favorable point estimate for eGFR slope and ranked highest by SUCRA, although the 95% credible intervals crossed the null. Those findings suggested a potentially favorable signal but did not establish treatment superiority.

Published 24 April 2026, this Bayesian network meta-analysis searched PubMed, the Cochrane Library, Web of Science, Scopus, and Embase from inception through March 2025. The investigators included randomized controlled trials enrolling adults with biopsy-proven IgA nephropathy. Treatments were methylprednisolone, mycophenolate mofetil, tacrolimus, Nefecon, iptacopan, and sibeprenlimab, each compared against placebo or supportive care. Outcomes included serious adverse events, eGFR slope, proteinuria, and urinary protein-to-creatinine ratio, with Bayesian random-effects models generating risk ratios or mean differences, 95% credible intervals, and SUCRA rankings. The network was centered on placebo or supportive care, allowing both direct and indirect comparisons.

For kidney function, Nefecon had the most favorable point estimate for eGFR slope within the treatment network and ranked highest in SUCRA analyses for that outcome. The corresponding credible intervals crossed the null, which limited confidence in the apparent advantage. Several between-treatment contrasts were also imprecise, leaving the eGFR pattern directional rather than definitive.

Proteinuria findings followed a different pattern across agents. Methylprednisolone showed the largest reductions versus placebo when urinary protein-to-creatinine ratio was assessed. Iptacopan and sibeprenlimab were also associated with reductions in proteinuria outcomes within the network. Overall, the results suggested proteinuria benefit across several therapies without resolving their relative positions with certainty.

Serious adverse event comparisons were mostly inconclusive because sparse data and wide uncertainty intervals limited precision across the network. Iptacopan showed a numerically lower point estimate for serious adverse events, but that signal remained uncertain. Prespecified subgroup analyses used interaction tests and did not suggest effect modification by baseline eGFR below 60 versus at least 60 mL/min/1.73 m². The authors concluded that sparse networks, heterogeneous regimens, and limited follow-up kept comparative estimates uncertain; that SUCRA rankings were exploratory rather than evidence of superiority; and that larger, longer-term, directly comparative trials with hard renal outcomes remain needed while current signals may inform individualized treatment decisions.