The long-acting C5 inhibitor, ravulizumab, is effective and safe in pediatric patients with atypical hemolytic uremic syndrome naïve to complement inhibitor treatment
Ariceta Iraola, Gema (Hospital Universitari Vall d'Hebron)
Dixon, B.P. (Renal Section. Department of Pediatrics. University of Colorado School of Medicine)
Kim, S.H. (Department of Pediatrics. Pusan National University Children's Hospital)
Kapur, G. (Faculty of Pediatric Sciences. Central Michigan University. Mount Pleasant)
Mauch, T. (Department of Nephrology and Hypertension. Division of Pediatrics. University of Utah)
Ortiz, S. (Clinical and Non-Clinical Pharmacology. Alexion Pharmaceuticals Inc.)
Vallee, M. (Biostatistics. Alexion Pharmaceuticals Inc.)
Denker, A.E. (Clinical Development. Alexion Pharmaceuticals Inc.)
Kang, H.G. (Division of Pediatric Nephrology. Department of Pediatrics. Seoul National University College of Medicine)
Greenbaum, L.A. (Division of Pediatric Nephrology. Emory University School of Medicine and Children's Healthcare of Atlanta)
Lovell, H.
Muff-Luett, M.
Malone, K.
Adeagbo, O.
Wilkerson, A.
Fraga Rodríguez, Gloria María (Institut d'Investigació Biomèdica Sant Pau)
Sarri, S.
Cheong, H.I.
Ahn, Y.H.
Han, K.H.

Data:	2021
Resum:	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. 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/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 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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Atypical hemolytic uremic syndrome ; Complement ; Eculizumab ; Hemolytic uremic syndrome ; Ravulizumab ; Thrombotic microangiopathy
Publicat a:	Kidney International, Vol. 100 Núm. 1 (july 2021) , p. 225-237, ISSN 1523-1755

DOI: 10.1016/j.kint.2020.10.046
PMID: 33307104

13 p, 1.8 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut de Recerca Sant Pau
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