The long-acting C5 inhibitor, ravulizumab, is effective and safe in pediatric patients with atypical hemolytic uremic syndrome naïve to complement inhibitor treatment.

Autor:	Ariceta G; Paediatric Nephrology Department, University Hospital Vall d'Hebron, Barcelona, Spain. Electronic address: gariceta@vhebron.net., 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., Vallee M; Biostatistics, Alexion Pharmaceuticals Inc., Boston, Massachusetts, USA., Denker AE; Clinical Development, Alexion Pharmaceuticals Inc., Boston, Massachusetts, USA., Kang HG; Division of Pediatric Nephrology, Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea., Greenbaum LA; Division of Pediatric Nephrology, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
Jazyk:	angličtina
Zdroj:	Kidney international [Kidney Int] 2021 Jul; Vol. 100 (1), pp. 225-237. Date of Electronic Publication: 2020 Dec 08.
DOI:	10.1016/j.kint.2020.10.046
Abstrakt:	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 m 2 . 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 x10 9 /L through week 26 and week 50, respectively. The median increase above baseline in estimated glomerular filtration rate was 80 and 94 mL/min/1.73m 2 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. (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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