Endopeptidase Cleavage of Anti-Glomerular Basement Membrane Antibodies in vivo in Severe Kidney Disease: An Open-Label Phase 2a Study
- PMID: 35260419
- PMCID: PMC8970456
- DOI: 10.1681/ASN.2021111460
Endopeptidase Cleavage of Anti-Glomerular Basement Membrane Antibodies in vivo in Severe Kidney Disease: An Open-Label Phase 2a Study
Abstract
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.
Keywords: Goodpasture syndrome; anti-GBM disease; clinical trial; endopeptidases; glomerulonephritis.
Copyright © 2022 by the American Society of Nephrology.
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Comment in
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Endopeptidase Therapy for Anti-Glomerular Basement Membrane Disease: Beware of Anti-Hinge Antibodies!J Am Soc Nephrol. 2022 Oct;33(10):1953-1954. doi: 10.1681/ASN.2022050609. Epub 2022 Aug 10. J Am Soc Nephrol. 2022. PMID: 35948435 Free PMC article. No abstract available.
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Authors' Reply: Endopeptidase Therapy for Anti-Glomerular Basement Membrane Disease: Beware of Anti-Hinge Antibodies!J Am Soc Nephrol. 2022 Oct;33(10):1954-1955. doi: 10.1681/ASN.2022070747. Epub 2022 Aug 10. J Am Soc Nephrol. 2022. PMID: 35948436 Free PMC article. No abstract available.
References
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- Hudson BG, Tryggvason K, Sundaramoorthy M, Neilson EG: Alport’s syndrome, Goodpasture’s syndrome, and type IV collagen. N Engl J Med 348: 2543–2556, 2003 - PubMed
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- Kidney Disease: Improving Global Outcomes Glomerular Diseases Work Group : KDIGO 2021 clinical practice guideline for the management of glomerular diseases. Available at: https://kdigo.org/guidelines/gd/
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