Eculizumab Safety: Five-Year Experience From the Global Atypical Hemolytic Uremic Syndrome Registry
Introduction: Eculizumab has transformed outcomes for patients with atypical hemolytic uremic syndrome (aHUS). Its efficacy and safety profile was well characterized in the clinical trial program. The long-term safety profile was not previously assessed or compared against nontreated patients in an...
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| Format: | Article |
| Language: | English |
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Elsevier
2019-11-01
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| Series: | Kidney International Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024919314378 |
| _version_ | 1818524839571357696 |
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| author | Eric Rondeau Spero R. Cataland Imad Al-Dakkak Benjamin Miller Nicholas J.A. Webb Daniel Landau, MD |
| author_facet | Eric Rondeau Spero R. Cataland Imad Al-Dakkak Benjamin Miller Nicholas J.A. Webb Daniel Landau, MD |
| author_sort | Eric Rondeau |
| collection | DOAJ |
| description | Introduction: Eculizumab has transformed outcomes for patients with atypical hemolytic uremic syndrome (aHUS). Its efficacy and safety profile was well characterized in the clinical trial program. The long-term safety profile was not previously assessed or compared against nontreated patients in an observational registry setting. Methods: The Global aHUS Registry recruits patients with clinical diagnoses of aHUS. This analysis includes baseline characteristics and targeted safety events from adult and pediatric patients who were “ever treated” versus “never treated” with eculizumab in the first 5 years of the registry, through January 26, 2017. Results: Overall, 1321 patients (adult, n = 842; pediatric, n = 479; ever treated, n = 865; never treated, n = 456) were enrolled. A higher proportion of ever-treated versus never-treated adult and pediatric patients had renal, cardiovascular, pulmonary, central nervous system, gastrointestinal symptoms, and hepatic impairment. No differences in safety event rates between ever-treated and never-treated patients were observed, except serious infections in pediatric patients (5.15 versus 1.12 events/100 patient-years for ever- and never-treated patients, respectively). Deaths were more frequent in adult (4.7% and 9.9% of ever- and never-treated patients) compared with pediatric patients (1.8% of ever-treated patients; no deaths in never-treated patients).Three meningococcal infections were reported in ever-treated patients; 1 infection led to a fatal outcome. Conclusion: In this large observational dataset covering 5 years of registry enrollment, no new safety concerns were identified for adult or pediatric eculizumab-treated patients with aHUS, confirming a positive benefit−risk profile in a real-world setting. Keywords: atypical hemolytic uremic syndrome, complement, thrombotic microangiopathy, safety |
| first_indexed | 2024-12-11T06:02:06Z |
| format | Article |
| id | doaj.art-f4c30169aad14443b7d1e00854abb943 |
| institution | Directory Open Access Journal |
| issn | 2468-0249 |
| language | English |
| last_indexed | 2024-12-11T06:02:06Z |
| publishDate | 2019-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Kidney International Reports |
| spelling | doaj.art-f4c30169aad14443b7d1e00854abb9432022-12-22T01:18:27ZengElsevierKidney International Reports2468-02492019-11-0141115681576Eculizumab Safety: Five-Year Experience From the Global Atypical Hemolytic Uremic Syndrome RegistryEric Rondeau0Spero R. Cataland1Imad Al-Dakkak2Benjamin Miller3Nicholas J.A. Webb4Daniel Landau, MD5Urgences Néphrologiques et Transplantation Rénale, Hôpital Tenon, and Sorbonne Université, Paris, France; Correspondence: Eric Rondeau, Urgences Néphrologiques et Transplantation Rénale, Hôpital Tenon, AP-HP, 4 Rue de la Chine, Paris, France 75020.Division of Hematology, The Ohio State University, Wexner Medical Center, Columbus, Ohio, USAGlobal Epidemiology, Alexion Pharmaceuticals, Inc., Boston, Massachusetts, USAGlobal Epidemiology, Alexion Pharmaceuticals, Inc., Boston, Massachusetts, USADepartment of Paediatric Nephrology, University of Manchester, Royal Manchester Children's Hospital, Manchester, UKSchneider Children's Medical Center, Sackler School of Medicine, Petach Tikva, IsraelIntroduction: Eculizumab has transformed outcomes for patients with atypical hemolytic uremic syndrome (aHUS). Its efficacy and safety profile was well characterized in the clinical trial program. The long-term safety profile was not previously assessed or compared against nontreated patients in an observational registry setting. Methods: The Global aHUS Registry recruits patients with clinical diagnoses of aHUS. This analysis includes baseline characteristics and targeted safety events from adult and pediatric patients who were “ever treated” versus “never treated” with eculizumab in the first 5 years of the registry, through January 26, 2017. Results: Overall, 1321 patients (adult, n = 842; pediatric, n = 479; ever treated, n = 865; never treated, n = 456) were enrolled. A higher proportion of ever-treated versus never-treated adult and pediatric patients had renal, cardiovascular, pulmonary, central nervous system, gastrointestinal symptoms, and hepatic impairment. No differences in safety event rates between ever-treated and never-treated patients were observed, except serious infections in pediatric patients (5.15 versus 1.12 events/100 patient-years for ever- and never-treated patients, respectively). Deaths were more frequent in adult (4.7% and 9.9% of ever- and never-treated patients) compared with pediatric patients (1.8% of ever-treated patients; no deaths in never-treated patients).Three meningococcal infections were reported in ever-treated patients; 1 infection led to a fatal outcome. Conclusion: In this large observational dataset covering 5 years of registry enrollment, no new safety concerns were identified for adult or pediatric eculizumab-treated patients with aHUS, confirming a positive benefit−risk profile in a real-world setting. Keywords: atypical hemolytic uremic syndrome, complement, thrombotic microangiopathy, safetyhttp://www.sciencedirect.com/science/article/pii/S2468024919314378 |
| spellingShingle | Eric Rondeau Spero R. Cataland Imad Al-Dakkak Benjamin Miller Nicholas J.A. Webb Daniel Landau, MD Eculizumab Safety: Five-Year Experience From the Global Atypical Hemolytic Uremic Syndrome Registry Kidney International Reports |
| title | Eculizumab Safety: Five-Year Experience From the Global Atypical Hemolytic Uremic Syndrome Registry |
| title_full | Eculizumab Safety: Five-Year Experience From the Global Atypical Hemolytic Uremic Syndrome Registry |
| title_fullStr | Eculizumab Safety: Five-Year Experience From the Global Atypical Hemolytic Uremic Syndrome Registry |
| title_full_unstemmed | Eculizumab Safety: Five-Year Experience From the Global Atypical Hemolytic Uremic Syndrome Registry |
| title_short | Eculizumab Safety: Five-Year Experience From the Global Atypical Hemolytic Uremic Syndrome Registry |
| title_sort | eculizumab safety five year experience from the global atypical hemolytic uremic syndrome registry |
| url | http://www.sciencedirect.com/science/article/pii/S2468024919314378 |
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