Sistema de Salut de Catalunya
Institut Català de la Salut
[Ariceta G] Servei de Nefrologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Dixon BP] Renal Section, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA. [Kim SH] Department of Pediatrics, Pusan National University Children's Hospital, Yangsan, Korea. [Kapur G] Faculty of Pediatric Sciences, Central Michigan University, Mount Pleasant, Michigan, USA. [Mauch T] Division of Pediatric Nephrology, University of Nebraska Medical Center, Omaha Children’s Hospital and Medical Center, Omaha, Nebraska, USA. Department of Nephrology and Hypertension, Division of Pediatrics, University of Utah, Salt Lake City, Utah, USA. [Ortiz S] Clinical and Non-Clinical Pharmacology, Alexion Pharmaceuticals Inc., Boston, Massachusetts, USA
Vall d'Hebron Barcelona Hospital Campus
2022-07-18T10:36:04Z
2022-07-18T10:36:04Z
2021-07
Eculizumab; Ravulizumab; Thrombotic microangiopathy
Eculizumab; Ravulizumab; Microangiopatía trombótica
Eculizumab; Ravulizumab; Microangiopatia trombòtica
Ravulizumab, a long-acting complement C5 inhibitor engineered from eculizumab, allows extending maintenance dosing from every 2-3 weeks to every 4-8 weeks depending on bodyweight. Here, we evaluated the efficacy and safety of ravulizumab in complement inhibitor-naïve children (under 18 years) with atypical hemolytic uremic syndrome. In this phase III, single-arm trial, ravulizumab was administered every eight weeks in patients 20 kg and over, and four weeks in patients under 20 kg. The primary endpoint was a complete thrombotic microangiopathy response (normalization of platelet count and lactate dehydrogenase, and a 25% or more improvement in serum creatinine) through 26 weeks. Secondary endpoints included change in hematologic parameters and kidney function. 18 patients with a median age of 5.2 years were evaluated. At baseline, symptoms of atypical hemolytic uremic syndrome outside the kidney were present in 72.2% of patients and 38.9% had been in intensive care. Baseline estimated glomerular filtration rate was 22 mL/min/1.73 m2. By week 26, 77.8% of patients achieved a complete thrombotic microangiopathy response; 94.4%, 88.9% and 83.3% of patients achieved platelet normalization, lactate dehydrogenase normalization and a 25% or more improvement in serum creatinine, respectively. By week 50, 94.4% patients had achieved a complete thrombotic microangiopathy response. Median improvement in platelet count was 246 and 213 x109/L through week 26 and week 50, respectively. The median increase above baseline in estimated glomerular filtration rate was 80 and 94 mL/min/1.73m2 through week 26 and week 50, respectively. No unexpected adverse events, deaths, or meningococcal infections occurred. Thus, ravulizumab rapidly improved hematologic and kidney parameters with no unexpected safety concerns in complement inhibitor-naïve children with atypical hemolytic uremic syndrome.
Article
Published version
English
Síndrome hemolíticourèmica - Tractament; Nefrologia pediàtrica; DISEASES::Male Urogenital Diseases::Urologic Diseases::Kidney Diseases::Uremia::Hemolytic-Uremic Syndrome::Atypical Hemolytic Uremic Syndrome; Other subheadings::Other subheadings::Other subheadings::/drug therapy; ENFERMEDADES::enfermedades urogenitales masculinas::enfermedades urológicas::enfermedades renales::uremia::síndrome hemolítico-urémico::síndrome hemolítico urémico atípico; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
Elsevier
Kidney International;100(1)
https://doi.org/10.1016/j.kint.2020.10.046
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
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