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Lookup NU author(s): Professor David KavanaghORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Rationale & Objective: Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) caused by complement dysregulation. Ravulizumab is a complement C5 inhibitor (C5i) approved for the treatment of aHUS. This analysis assessed long-term outcomes of ravulizumab in adults and pediatric patients with aHUS. Study Design: This analysis reports 2-year data from two phase 3, single-arm studies. Setting & Participants: One study included C5i-naive adults (NCT02949128) and the other included two cohorts of pediatric patients (C5i-naive and those who switched to ravulizumab from eculizumab [pediatric switch patients]; NCT03131219). Exposure(s): Patients received intravenous ravulizumab every 4–8 weeks, with the dose depending on body weight. Outcomes: The primary endpoint in the studies of C5i-naive patients was complete TMA response, which consisted of platelet count normalization, lactate dehydrogenase normalization, and ≥25% improvement in serum creatinine from baseline, at two consecutive assessments at least 4 weeks apart. Analytical Approach: All analyses used descriptive statistics. No formal statistical comparisons were performed. Results: In total, 86 and 92 patients were included in efficacy and safety analyses, respectively. Complete TMA response rates over 2 years were 61% and 90% in C5i-naive adults and pediatric patients, respectively. The median increase in eGFR from baseline was maintained over 2 years in C5i-naive adults (35 mL/min/1.73m2 ) and pediatric patients (82.5 mL/min/1.73m2 ). Most adverse events and serious adverse events occurred during the first 26 weeks. No meningococcal infections were reported. Improvement in the Functional Assessment of Chronic Illness Therapy – Fatigue score achieved by 26 weeks was maintained over 2 years. Journal Pre-proof 3 Limitations: Limitations were the small sample of pediatric switch patients and limited availability of genetic data. Conclusions: Long-term treatment with ravulizumab is well tolerated and associated with improved hematological and renal parameters and quality of life in adults and pediatric patients with aHUS.
Author(s): Dixon BP, Kavanagh D, Aris ADM, Adams B, Kang HG, Wang E, Garlo K, Ogawa M, Amancha P, Chakravarty S, Heyne N, Kim SH, Cataland S, Yoon S, Miyakawa Y, Luque Y, Muff-Luett M, Tanaka L, Greenbaum LA
Publication type: Article
Publication status: Published
Journal: Kidney Medicine
Year: 2024
Pages: epub ahead of print
Online publication date: 14/06/2024
Acceptance date: 20/03/2024
Date deposited: 11/07/2024
ISSN (electronic): 2590-0595
Publisher: Elsevier BV
URL: https://doi.org/10.1016/j.xkme.2024.100855
DOI: 10.1016/j.xkme.2024.100855
Data Access Statement: Alexion will consider requests for disclosure of clinical study participant-level data provided that participant privacy is assured through methods like data de-identification, pseudonymization, or anonymization (as required by applicable law), and if such disclosure was included in the relevant study informed consent form or similar documentation. Qualified academic investigators may request participant-level clinical data and supporting documents (statistical analysis plan and protocol) pertaining to Alexion sponsored studies. Further details regarding data availability and instructions for requesting information are available in the Alexion Clinical Trials Disclosure and Transparency Policy at https://alexion.com/our-research/research-anddevelopment. Link to Data Request Form (https://alexion.com/contactalexion/medical-information)
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