Efficacy and safety of complement inhibitors in IgAN: a systematic review and meta-analysis

The benefits and risks of complement inhibitors for the treatment of immunoglobulin A nephropathy (IgAN) remain uncertain. We conducted this systematic review and meta-analysis to compare the efficacy and safety of complement inhibitors vs. placebo.

The PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases were searched until December 20, 2024. This study analyzed the effects of complement inhibitors on the 24-h urinary protein-to-creatinine ratio (24-h UPCR), estimated glomerular filtration rate (eGFR), and the incidence of adverse events in IgAN.

In total, 4 studies with 398 patients were included in the systematic review and meta-analysis. In patients with IgAN, complement inhibitors significantly attenuated the decline in eGFR [MD = 3.50 ml/min/1.73 m², 95% CI (0.44, 6.57), P < 0.05] and demonstrated superior efficacy in reducing proteinuria markers: a 24-h UPCR reduction of -0.71 g/g [95% CI (-0.91, -0.50), P < 0.05] was observed. Safety analyses revealed comparable tolerability between the intervention and control groups, with no statistically significant difference in adverse event incidence [RR = 0.91, 95% CI (0.74, 1.11), P = 0.35].

Complement inhibitors appear to confer renal protective effects without increasing the risk of adverse events in patients with IgAN.