Eculizumab Safety: Five-Year Experience From the Global Atypical Hemolytic Uremic Syndrome Registry

Eric Rondeau; Spero R Cataland; Imad Al-Dakkak; Benjamin Miller; Nicholas J A Webb; Daniel Landau

doi:10.1016/j.ekir.2019.07.016

Eculizumab Safety: Five-Year Experience From the Global Atypical Hemolytic Uremic Syndrome Registry

Kidney Int Rep. 2019 Aug 2;4(11):1568-1576. doi: 10.1016/j.ekir.2019.07.016. eCollection 2019 Nov.

Authors

Eric Rondeau¹, Spero R Cataland², Imad Al-Dakkak³, Benjamin Miller³, Nicholas J A Webb⁴, Daniel Landau⁵

Affiliations

¹ Urgences Néphrologiques et Transplantation Rénale, Hôpital Tenon, and Sorbonne Université, Paris, France.
² Division of Hematology, The Ohio State University, Wexner Medical Center, Columbus, Ohio, USA.
³ Global Epidemiology, Alexion Pharmaceuticals, Inc., Boston, Massachusetts, USA.
⁴ Department of Paediatric Nephrology, University of Manchester, Royal Manchester Children's Hospital, Manchester, UK.
⁵ Schneider Children's Medical Center, Sackler School of Medicine, Petach Tikva, Israel.

Abstract

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; safety; thrombotic microangiopathy.