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.Clinical Trial registration number: EUDRACT 2016-004082-39 https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-001377-28/results.

Department of Clinical Sciences Lund University Lund Sweden

Department of Health Technologies Tallinn University of Technology Tallinn Estonia

Department of Internal Medicine 4 Medical University Innsbruck Innsbruck Austria

Department of Laboratory Medicine University of Gothenburg Gothenburg Sweden

Department of Medical Sciences Uppsala University Uppsala Sweden

Department of Medicine Imperial College London London United Kingdom

Department of Nephrology and Department of Health Medicine and Caring Sciences Linköping University Linköping Sweden

Department of Nephrology and Organ Transplantation Université Paul Sabatier Toulouse France

Department of Nephrology Charles University and General University Hospital Prague Czech Republic

Department of Nephrology Hemodialysis Apheresis and Kidney Transplantation EriCHU Grenoble Alpes Grenoble France

Department of Nephrology P Københavns universitet Copenhagen Denmark

Department of Pathology Leiden University Medical Center Leiden the Netherlands

Department of Renal Medicine Karolinska University Hospital and CLINTEC Karolinska Institutet Stockholm Sweden

Hansa Biopharma Lund Sweden

Neohrology service Centre Hospitalier Regional Lille University Lille France

Nephrology Service Hôpital Bichat Université de Paris Paris France

Urgences Néphrologiques et Transplantation Rénale Paris France

J Am Soc Nephrol. 2022 Oct;33(10):1953-1954. doi: 10.1681/ASN.2022050609. PubMed

J Am Soc Nephrol. 2022 Oct;33(10):1954-1955. doi: 10.1681/ASN.2022070747. PubMed

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Risk Stratification to Predict Renal Survival in Anti-Glomerular Basement Membrane Disease