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

Autor: Sunil Babu, Guilia Antognoli, Elena Gutierréz, Yoshitaka Miyakawa, Moglie Le Quintrec, Jan Menne, David J. Kavanagh, Tatiana Kirsanova, Edwin K.S. Wong, Maria Vinogradova, Philip Campbell, Guillaume Favre, Michael Fischereder, Spero R. Cataland, Iino Fumie, Hermann Haller, Vladimir A. Dobronravov, Paramit Chowdhury, Guillaume Jeantet, Marie Scully, Sonia Boyer-Suavet, Thomas D. Barbour, Yosu Luque, Leonardo Caroti, Stephan Ortiz, Shashi K. Nagaraj, Cyril Garrouste, Masayoshi Okumi, Anja Gaeckler, Maria Cappuccilli, Chiu-Ching Huang, Anja Muhlfeld, Gema Ariceta, Gaetano La Manna, Eric Rondeau, Nils Heyne, Giorgia Comai, Natalia Ramos Terrada, Eric Goffin, Paola Rodriguez, Gregory Greenwood, Eugene Swenson, Barbara Seitz-Polski, Nilufer Broeders, Gowthami M. Arepally, Manuel Praga Terente, Marc Vallee, Johan Morelle, Siân V. Griffin, Nicole Lietar, Doyeun Oh, Theo Kasimatis, I-Ru Chen, Ulf Schönermarck, Susan Huang, Jin Seok Kim, Fiona G. Brown, François Provôt, Lino Cirami, Sung-Soo Yoon, Yahsou Delmas
Přispěvatelé: UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, Sorbonne Université (SU), The Ohio State University Press, Hannover Medical School [Hannover] (MHH)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Kidney international, Vol. 97, no.6, p. 1287-1296 (2020)
Kidney International
Kidney International, Nature Publishing Group, 2020, 97, pp.1287-1296. ⟨10.1016/j.kint.2020.01.035⟩
Kidney international, Vol. 97, no. 6, p. 1287-1296 (2020)
ISSN: 0085-2538
1523-1755
DOI: 10.1016/j.kint.2020.01.035⟩
Popis: Ravulizumab is a long-acting C5 inhibitor engineered from eculizumab with increased elimination half-life, allowing an extended dosing interval from two to eight weeks. Here we evaluate the efficacy and safety of ravulizumab in adults with atypical hemolytic uremic syndrome presenting with thrombotic microangiopathy. In this global, phase 3, single arm study in complement inhibitor-naive adults (18 years and older) who fulfilled diagnostic criteria for atypical hemolytic uremic syndrome, enrolled patients received ravulizumab through a 26-week initial evaluation period. The primary endpoint was complete thrombotic microangiopathy response defined as normalization of platelet count and lactate dehydrogenase and 25% or more improvement in serum creatinine. Secondary endpoints included changes in hematologic variables and renal function. Safety was also evaluated. Ravulizumab treatment resulted in an immediate, complete, and sustained C5 inhibition in all patients. Complete thrombotic microangiopathy response was achieved in 53.6% of patients. Normalization of platelet count, lactate dehydrogenase and 25% or more improvement in serum creatinine was achieved in 83.9%, 76.8% and 58.9% of patients, respectively. Improvement in estimated glomerular filtration rate by one or more stage was achieved in 68.1% of patients by day 183. No unexpected adverse events were reported across a safety analysis set of 58 patients. Four deaths occurred (three within one month of study initiation, including one in a patient excluded based on eligibility criteria after the first dose) with none considered treatment-related by the study investigator. Thus, treatment with ravulizumab once every eight weeks resulted in rapidly improved hematologic and renal endpoints with no unexpected adverse events in adults with atypical hemolytic uremic syndrome.
Databáze: OpenAIRE
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