New enzyme therapy shows promise in rare kidney disease, but antibody rebound remains a challenge
A clinical trial of imlifidase—an enzyme that rapidly strips antibodies from the bloodstream—offers insights into anti-GBM disease, a severe autoimmune kidney condition. Patients whose antibodies rebounded after treatment experienced worse kidney function, suggesting that controlling antibody rebound could be critical to improving outcomes in this hard-to-treat disease.
Originaltitel: Using imlifidase to elucidate the characteristics and importance of anti-GBM antibodies produced after start of treatment
<p>Background: Autoantibodies are common in glomerulonephritis, but the clinical benefit of rapid elimination has not been determined, even in anti-glomerular basement membrane (GBM) disease. Even less is known about the importance of autoantibody characteristics, including epitope specificity and immunoglobulin G (IgG) subclass distribution. We aimed to address this by characterizing the autoantibody profile in anti-GBM patients: we utilized samples from the GOOD-IDES-01 (treating GOODpastures disease with Imunoglobulin G Degrading Enzyme of Streptococcus pyogenous) ( identifier: NCT03157037) trial , where imlifidase, which cleaves all IgG in vivo within hours, was given to 15 anti-GBM patients.Methods: In the GOOD-IDES-01 trial, plasmapheresis was (re)started if anti-GBM antibodies rebounded. Serum samples were collected prospectively for 6 months and analyzed for anti-GBM epitope specificity using recombinant constructs of the E-A and E-B epitopes, IgG subclass using monoclonal antibodies, and anti-neutrophil cytoplasmic antibodies (ANCA). The results were correlated with clinical data.Results: Patients with a rebound (n = 10) tended to have lower eGFR at 6 months (11 vs 34 mL/min/1.73 m(2), P = .055), and patients with dialysis at 6 months had a higher E-B/E-A ratio at rebound (0.8 vs 0.5, P = .047). Moreover, two patients demonstrated increasing epitope restriction and several patients displayed a shift in subclass distribution at rebound. Six patients were double positive for ANCA. ANCA rebound was seen in 50% of patients; only one patient remained ANCA positive at 6 months.Conclusions: In this study, rebound of anti-GBM antibodies, especially if directed against the E-B epitope, was associated with a worse outcome. This supports the notion that all means should be used to eliminate anti-GBM antibodies. In this study ANCA was removed early and long-term by imlifidase and cyclophosphamide.</p>