Endopeptidase Cleavage of Anti-Glomerular Basement Membrane Antibodies in vivo in Severe Kidney Disease: An Open-Label Phase 2a Study

Fredrik Uhlin, Wladimir Szpirt, Andreas Kronbichler, Annette Bruchfeld, Inga Soveri, Lionel Rostaing, Eric Daugas, Arnaud Lionet, Nassim Kamar, Cedric Rafat, Marek Myslivecek, Vladimir Tesar, Anders Fernstrom, Christian Kjellman, Charlotte Elfving, Stephen McAdoo, Johan Molne, Ingeborg Bajema, Elisabeth Sonesson, Marten Segelmark

Research output: Contribution to journalArticlepeer-review


Background The prognosis for kidney survival is poor in patients presenting with circulating anti–glomerular basement membrane (GBM) antibodies and severe kidney injury. It is unknown if treatment with an endopeptidase that cleaves circulating and kidney bound IgG can alter the prognosis. Methods An investigator-driven phase 2a one-arm study (EudraCT 2016–004082–39) was performed in 17 hospitals in five European countries. A single dose of 0.25 mg/kg of imlifidase was given to 15 adults with circulating anti-GBM antibodies and an eGFR <15 ml/min per 1.73m2. All patients received standard treatment with cyclophosphamide and corticosteroids, but plasma exchange only if autoantibodies rebounded. The primary outcomes were safety and dialysis independency at 6 months. Results At inclusion, ten patients were dialysis dependent and the other five had eGFR levels between 7 and 14 ml/min per 1.73m2. The median age was 61 years (range 19–77), six were women, and six were also positive for anti–neutrophil cytoplasmic antibodies. Then 6 hours after imlifidase infusion, all patients had anti-GBM antibodies levels below the reference range of a prespecified assay. At 6 months 67% (ten out of 15) were dialysis independent. This is significantly higher compared with 18% (nine out of 50) in a historical control cohort (P<0.001, Fisher's exact test). Eight serious adverse events (including one death) were reported, none assessed as probably or possibly related to the study drug. Conclusions In this pilot study, the use of imlifidase was associated with a better outcome compared with earlier publications, without major safety issues, but the findings need to be confirmed in a randomized controlled trial.

Original languageEnglish
Pages (from-to)829-838
Number of pages10
JournalJournal of the American Society of Nephrology
Issue number4
Publication statusPublished - 2022 Apr

Subject classification (UKÄ)

  • Urology and Nephrology


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