Global aHUS Registry Analysis of Patients Switching to Ravulizumab From Eculizumab

Introduction: Atypical hemolytic uremic syndrome (aHUS) is a progressive rare disease that, if untreated, can result in severe organ damage and death. Ravulizumab, a next-generation terminal complement inhibitor, provides immediate, complete, and sustained complement C5 inhibition. Real-world data i...

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Main Authors: Franz Schaefer, Imad Al-Dakkak, Katerina Anokhina, David Cohen, Larry A. Greenbaum, Gema Ariceta
Format: Article
Language:English
Published: Elsevier 2024-09-01
Series:Kidney International Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2468024924017960
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author Franz Schaefer
Imad Al-Dakkak
Katerina Anokhina
David Cohen
Larry A. Greenbaum
Gema Ariceta
author_facet Franz Schaefer
Imad Al-Dakkak
Katerina Anokhina
David Cohen
Larry A. Greenbaum
Gema Ariceta
author_sort Franz Schaefer
collection DOAJ
description Introduction: Atypical hemolytic uremic syndrome (aHUS) is a progressive rare disease that, if untreated, can result in severe organ damage and death. Ravulizumab, a next-generation terminal complement inhibitor, provides immediate, complete, and sustained complement C5 inhibition. Real-world data in patients with aHUS who switched to ravulizumab from eculizumab are lacking. Methods: The Global aHUS Registry is a multicenter study (NCT01522183) collecting data on adult or pediatric patients with an aHUS diagnosis, regardless of treatment. Patient characteristics, genetic data, hematological and renal parameters, clinical events (e.g., dialysis and kidney transplantation), and adverse events (AEs) were extracted from patients who switched to ravulizumab from eculizumab up to July 3, 2023. Results: Overall, 60 patients switched to ravulizumab (adult: n = 43; pediatric: n = 17); 11 patients were excluded from effectiveness and genetic analyses (N = 49; adult: n = 40; pediatric: n = 9) because they received <3 months ravulizumab treatment and/or had >1 month between eculizumab discontinuation and ravulizumab initiation. Pathogenic complement variants were identified in 11 of 49 patients (22%); the most common was a complement factor H variant (n = 5/49 [10%]). During ravulizumab treatment, 20 AEs occurred in 13 patients, with no unexpected AEs and only 3 treatment-related AEs (infusion reaction, headaches, and fatigue). No meningococcal infections or deaths were reported. No new events of dialysis, kidney transplantation, or thrombotic microangiopathy were reported. Renal and hematological parameters remained stable after switching to ravulizumab. Conclusion: This is the first real-world cohort analysis of data from patients treated with ravulizumab and reinforces the real-world safety and effectiveness data of ravulizumab in patients with aHUS who switched from eculizumab.
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spelling doaj-art-13daf4d90a904443af6a7b4f7f55321e2025-08-20T03:21:18ZengElsevierKidney International Reports2468-02492024-09-01992648265610.1016/j.ekir.2024.06.020Global aHUS Registry Analysis of Patients Switching to Ravulizumab From EculizumabFranz Schaefer0Imad Al-Dakkak1Katerina Anokhina2David Cohen3Larry A. Greenbaum4Gema Ariceta5Division of Pediatric Nephrology, Heidelberg University Hospital, Heidelberg, Germany; Correspondence: Franz Schaefer, Heidelberg University Hospital, Im Neuenheimer Feld 672, Heidelberg 69120, Germany.Epidemiology, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, USADivision of Pediatric Nephrology, Heidelberg University Hospital, Heidelberg, Germany; Epidemiology, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, USA; Global Medical Affairs, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, USA; Department of Medicine, Columbia University Medical Center, New York, New York, USA; Division of Pediatric Nephrology, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia, USA; Department of Pediatric Nephrology, Vall d'Hebron Hospital, Barcelona, SpainDepartment of Medicine, Columbia University Medical Center, New York, New York, USADivision of Pediatric Nephrology, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia, USADepartment of Pediatric Nephrology, Vall d'Hebron Hospital, Barcelona, SpainIntroduction: Atypical hemolytic uremic syndrome (aHUS) is a progressive rare disease that, if untreated, can result in severe organ damage and death. Ravulizumab, a next-generation terminal complement inhibitor, provides immediate, complete, and sustained complement C5 inhibition. Real-world data in patients with aHUS who switched to ravulizumab from eculizumab are lacking. Methods: The Global aHUS Registry is a multicenter study (NCT01522183) collecting data on adult or pediatric patients with an aHUS diagnosis, regardless of treatment. Patient characteristics, genetic data, hematological and renal parameters, clinical events (e.g., dialysis and kidney transplantation), and adverse events (AEs) were extracted from patients who switched to ravulizumab from eculizumab up to July 3, 2023. Results: Overall, 60 patients switched to ravulizumab (adult: n = 43; pediatric: n = 17); 11 patients were excluded from effectiveness and genetic analyses (N = 49; adult: n = 40; pediatric: n = 9) because they received <3 months ravulizumab treatment and/or had >1 month between eculizumab discontinuation and ravulizumab initiation. Pathogenic complement variants were identified in 11 of 49 patients (22%); the most common was a complement factor H variant (n = 5/49 [10%]). During ravulizumab treatment, 20 AEs occurred in 13 patients, with no unexpected AEs and only 3 treatment-related AEs (infusion reaction, headaches, and fatigue). No meningococcal infections or deaths were reported. No new events of dialysis, kidney transplantation, or thrombotic microangiopathy were reported. Renal and hematological parameters remained stable after switching to ravulizumab. Conclusion: This is the first real-world cohort analysis of data from patients treated with ravulizumab and reinforces the real-world safety and effectiveness data of ravulizumab in patients with aHUS who switched from eculizumab.http://www.sciencedirect.com/science/article/pii/S2468024924017960atypical hemolytic uremic syndromeeculizumabreal-world dataravulizumaboutcomespatient characteristics
spellingShingle Franz Schaefer
Imad Al-Dakkak
Katerina Anokhina
David Cohen
Larry A. Greenbaum
Gema Ariceta
Global aHUS Registry Analysis of Patients Switching to Ravulizumab From Eculizumab
Kidney International Reports
atypical hemolytic uremic syndrome
eculizumab
real-world data
ravulizumab
outcomes
patient characteristics
title Global aHUS Registry Analysis of Patients Switching to Ravulizumab From Eculizumab
title_full Global aHUS Registry Analysis of Patients Switching to Ravulizumab From Eculizumab
title_fullStr Global aHUS Registry Analysis of Patients Switching to Ravulizumab From Eculizumab
title_full_unstemmed Global aHUS Registry Analysis of Patients Switching to Ravulizumab From Eculizumab
title_short Global aHUS Registry Analysis of Patients Switching to Ravulizumab From Eculizumab
title_sort global ahus registry analysis of patients switching to ravulizumab from eculizumab
topic atypical hemolytic uremic syndrome
eculizumab
real-world data
ravulizumab
outcomes
patient characteristics
url http://www.sciencedirect.com/science/article/pii/S2468024924017960
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