Efficacy and safety of eculizumab in patients with anti-glomerular basement membrane disease: an investigator-initiated, open-label, phase II clinical trial

BACKGROUND: Anti-glomerular basement membrane disease (GBM) is the most severe type of autoimmune kidney diseases, and is associated with the overactivation of the complement cascade. We aimed to evaluate the efficacy and safety of eculizumab, a complement C5 blocker that targets terminal pathways, in patients with anti-GBM disease. METHODS: An investigator-initiated, open-label, phase II clinical trial was conducted (NCT06513338). Eligible participants were aged at least 18 years diagnosed with anti-GBM disease at our center. Eculizumab was given at a dose of 900 mg for 4 consecutive weeks, followed by 1200 mg every other week for the subsequent 8 weeks. All patients received standard of care of the disease. The primary endpoint was end-stage kidney disease (ESKD) events at 6 months. Patients with anti-GBM disease diagnosed at the same center during the same period who did not receive eculizumab were retrospectively identified as contemporaneous controls. RESULTS: Between March 2024 and April 2025, a total of 16 patients were enrolled to receive eculizumab treatment, along with 40 contemporaneous controls. ESKD events were 25.0% at 6 months following eculizumab treatment, compared to that of 52.5% in contemporaneous controls. Of 7 patients requiring dialysis, 3 (42.9%) achieved kidney function recovery, compared to that of 8.7% in contemporaneous controls. Eculizumab treatment was associated with improved kidney function injury, while complement inhibition was evidenced by decreased urinary C5a and soluble C5b-9 concentrations and plasma CH50. Adverse events were reported in 2 participants and others showed well tolerance to eculizumab administration during the trial. CONCLUSIONS: Eculizumab treatment showed improvement in kidney survival and kidney function recovery in addition to standard of care. Eculizumab was generally well tolerated in patients with anti-GBM disease. Given the exploratory nature and sample size of this study, larger, adequately powered prospective studies are warranted to confirm and extend these findings.