The long-acting C5 inhibitor, Ravulizumab, is effective and safe in adult patients with atypical hemolytic uremic syndrome naïve to complement inhibitor treatment
Eric Rondeau, Marie Scully, Gema Ariceta, Tom Barbour, Spero Cataland, Nils Heyne, Yoshitaka Miyakawa, Stephan Ortiz, Eugene Swenson, Marc Vallee, Sung-Soo Yoon, David Kavanagh, Hermann Haller, 311 Study Group, Sunil Babu, Nilufer Broeders, Nicole Lietar, Fiona Brown, Philip Campbell, Paramit Chowdhury, Theo Kasimatis, Lino Cirami, Leonardo Caroti, Guilia Antognoli, Yahsou Delmas, Vladimir Dobronravov, Anja Gaeckler, Cyril Garrouste, Gregory Greenwood, Siân Griffin, Chiu-Ching Huang, I-Ru Chen, Susan Huang, Jin Seok Kim, Gaetano La Manna, Giorgia Comai, Maria Cappuccilli, Moglie Le Quintrec, Guillaume Jeantet, Iino Fumie, Yosu Luque, Jan Menne, Johan Morelle, Eric Goffin, Anja Muhlfeld, Shashi Nagaraj, Gowthami Arepally, Doyeun Oh, Masayoshi Okumi, Manuel Praga Terente, Elena Gutierréz, Paola Rodriguez, Francois Provot, Ulf Schönermarck, Michael Fischereder, Natalia Ramos Terrada, Barbara Seitz-Polski, Guillaume Favre, Sonia Boyer-Suavet, Maria Vinogradova, Tatiana Kirsanova, Edwin K S Wong, Eric Rondeau, Marie Scully, Gema Ariceta, Tom Barbour, Spero Cataland, Nils Heyne, Yoshitaka Miyakawa, Stephan Ortiz, Eugene Swenson, Marc Vallee, Sung-Soo Yoon, David Kavanagh, Hermann Haller, 311 Study Group, Sunil Babu, Nilufer Broeders, Nicole Lietar, Fiona Brown, Philip Campbell, Paramit Chowdhury, Theo Kasimatis, Lino Cirami, Leonardo Caroti, Guilia Antognoli, Yahsou Delmas, Vladimir Dobronravov, Anja Gaeckler, Cyril Garrouste, Gregory Greenwood, Siân Griffin, Chiu-Ching Huang, I-Ru Chen, Susan Huang, Jin Seok Kim, Gaetano La Manna, Giorgia Comai, Maria Cappuccilli, Moglie Le Quintrec, Guillaume Jeantet, Iino Fumie, Yosu Luque, Jan Menne, Johan Morelle, Eric Goffin, Anja Muhlfeld, Shashi Nagaraj, Gowthami Arepally, Doyeun Oh, Masayoshi Okumi, Manuel Praga Terente, Elena Gutierréz, Paola Rodriguez, Francois Provot, Ulf Schönermarck, Michael Fischereder, Natalia Ramos Terrada, Barbara Seitz-Polski, Guillaume Favre, Sonia Boyer-Suavet, Maria Vinogradova, Tatiana Kirsanova, Edwin K S Wong
Abstract
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-naïve 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.
Keywords: atypical hemolytic uremic syndrome; complement; eculizumab; hemolytic uremic syndrome; ravulizumab; thrombotic microangiopathy.
Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
Source: PubMed