Comparative effectiveness and safety for the treatments despite optimized renin-angiotensin system blockade among IgA nephropathy patients at high-risk of disease progression: A network meta-analysis of randomized controlled trials

Objective: Approximately 20-40% of IgA nephropathy patients would develop end-stage renal disease, for whom safety concerns remained a major setback when using conventional pharmaceutical treatments. Evidence is lacking for optimal selection of effective and safe pharmaceuticals to slow the disease progression. To compare the effectiveness and safety profile of different treatments despite optimized RAS blockade for IgA nephropathy patients at high-risk of disease progression.

Study design: PubMed, ScienceDirect and Web of science databases published from 1990 to March 18th, 2023 without language restriction. Immunosuppressant and cortico-steroid treatments were considered as two independent regimens.

Results: Fifteen trials with 1,983 participants were evaluated for the occurrence of five outcomes. For ESRD, dapagliflozin was superior to placebo (RR: 0.30; 95% CI 0.11, 0.80), immunosuppressant (RR:0.14; 95% CI 0.02,0.81) and RAS (RR:0.10; 95% CI 0.01,0.69). Glucocorticoid was superior to placebo (RR: 0.71; 95%CI 0.52,0.99). For clinical remission, immunosuppressant was superior to placebo (RR: 2.71; 95%CI 1.16, 6.31) and RAS monotherapy (RR: 2.87; 95%CI 1.60, 5.17). For 50% reduction in 24 h proteinuria or UPCR, immunosuppressant was superior to placebo (RR: 2.71; 95%CI 1.16, 6.31) and RAS monotherapy (RR: 2.40; 95%CI 1.04, 5.55). For SAE, dapagliflozin was superior to glucocorticoid (RR: 0.22; 95%CI 0.09, 0.54), whereas glucocorticoid was inferior to placebo (RR: 2.91; 95%CI 1.39, 6.07). Cluster ranking showed dapagliflozin appeared to have the lowest SAE risk and the best comparative therapeutic efficacy in preventing ESRD.

Conclusions: The current findings highlighted dapagliflozin was a promising pharmaceutical treatment alternative to achieve optimal outcomes for IgA nephropathy patients at high risk of disease progression.

Registration: PROSPERO CRD42022374418.