Long-Term Efficacy and Safety of the Long-Acting Complement C5 Inhibitor Ravulizumab for the Treatment of Atypical Hemolytic Uremic Syndrome in Adults
Thomas Barbour, Marie Scully, Gema Ariceta, Spero Cataland, Katherine Garlo, Nils Heyne, Yosu Luque, Jan Menne, Yoshitaka Miyakawa, Sung‐Soo Yoon, David Kavanagh, Sunil Babu, Nilüfer Broeders, Nicole Lietar, Fiona G. Brown, Philip Campbell, Josep M. Campistol, 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 S. Huang, Jin Seok Kim, Gaetano La Manna, Moglie Le Quintrec, Guillaume Jeantet, Iino Fumie, Éric Rondeau, Hermann Haller, J Morelle, Éric Goffin, Anja Mühlfeld, Shashi Nagaraj, Gowthami M. Arepally, Doyeun Oh, Masayoshi Okumi, Manuel Praga Terente, François Provôt, Ulf Schönermarck, Michael Fischereder, Natàlia Ramos Terrada, Barbara Seitz‐Polski, Guillaume Favrè, Sonia Boyer‐Suavet, Maria Vinogradova, Tatiana Kirsanova, Edwin Wong
Abstract
INTRODUCTION: Atypical hemolytic uremic syndrome (aHUS) is a rare, complex, multisystem disease of dysregulated complement activity, characterized by progressive thrombotic microangiopathy (TMA), acute kidney injury, and multiorgan dysfunction, which often progresses to chronic kidney disease. Results from the prospective clinical trial of ravulizumab (NCT02949128) reveal rapid resolution of TMA in patients with aHUS, with sustained efficacy and safety in a 26-week initial evaluation period. METHODS: The aim of this analysis was to characterize the long-term efficacy and the safety profile of ravulizumab in adults with aHUS who had completed the initial evaluation period of the trial. Complete TMA response, hematologic and kidney functions, and safety were evaluated for all patients available for follow-up in the extension period (median follow-up: 76.7 weeks; range: 0.6-118.3). This trial included a total of 58 patients, 49 of whom entered the extension period. RESULTS: A total of 4 additional patients achieved complete TMA response during the follow-up period. Normalization of platelet count, serum lactate dehydrogenase (LDH), and hemoglobin observed in the 26-week initial evaluation period was sustained until the last available follow-up, as were the improvements in the estimated glomerular filtration rate (eGFR) and patient quality of life. All efficacy endpoints were correlated with the sustained inhibition of complement C5. Most adverse events (AEs) occurred early during the initial evaluation period and decreased substantially during the extension period. No patient developed a meningococcal infection or died during the extension period. CONCLUSION: This analysis reveals that ravulizumab administered every 8 weeks is efficacious with an acceptable safety profile for the long-term treatment of adults with aHUS and provides additional clinical benefit beyond 6 months of treatment.