The immunoglobulin g degrading enzyme imlifidase for the treatment of anti-gbm disease: The good-ides 01 trial

Background: Anti-GBM disease is an ultra-rare small vessel vasculitis with a yearly incidence below 2 per million. Most cases present with rapidly progressive glomerulonephritis and despite aggressive treatment with plasma exchange and cyclophosphamide renal survival is poor, at least for those presenting with advanced kidney injury. Imlifidase has been shown to cause depletion of circulating and kidney bound anti-GBM within a few hours, but it is not known if this leads to an improved outcome. Methods: We conducted an international multi-center one-arm open-label study giving a single dose of 0.25mg/kg of imlifidase (non-proprietary name for IdeS = Immunoglobulin G Degrading Enzyme of Streptococcus pyogenes) on top of standard of care (ClinicalTrials.gov: NCT03157037). Main inclusion criteria were eGFR <15 ml/min/1.73m2 and circulating anti-GBM antibodies. Main exclusion criteria were moderate or severe lung hemorrhage, dialysis dependency > 5 days and/or oliguria >48 hours. The primary outcome was dialysis free survival at 6 months. Results: At 17 tertiary referral hospitals in 5 European countries 15 patients (6 women) were recruited between June 2017 and January 2020. Their median age was 60 years (range 19-77) and 5 were double positive for anti-GBM and ANCA. At inclusion 10 patients were dialysis dependent including 5 that were oliguric/anuric; the remaining 5 patients had eGFR of 7-14 ml/min. 6h hours after imflidase no patient had anti-GBM above the reference range. Return of antibodies prompting plasma exchange was seen in 10 patient 4 to 22 days after imlifidase (median 7 days), and they received a median of 8 session (range 2-17). At six months 10 patients were dialysis independent (median eGFR 27 ml/min, range 16-67), one was dead and 4 had developed ESRD. A favorable response was seen also in some patients that were anuric on inclusion and in some with 100% crescents. The safety profile was good; there were 7 serious adverse events (SAEs) reported but no serious unexpected suspected adverse reaction (SUSAR). Conclusions: Imflidase leads to rapid clearance of anti-GBM which seems to widen the window of opportunity for treatment thereby increasing the chance of renal survival in difficult to treat patients with anti-GBM disease.