Eculizumab discontinuation in children and adults with atypical hemolytic-uremic syndrome: a prospective multicenter study
Fadi Fakhouri, Marc Fila, Aurélie Hummel, David Ribes, Anne-Laure Sellier-Leclerc, Simon Ville, Claire Pouteil-Noble, Jean-Philippe Coindre, Moglie Le Quintrec, Eric Rondeau, Olivia Boyer, François Provôt, Djamal Djeddi, William Hanf, Yahsou Delmas, Ferielle Louillet, Annie Lahoche, Guillaume Favre, Valérie Châtelet, Emma Allain Launay, Claire Presne, Ariane Zaloszyc, Sophie Caillard, Stéphane Bally, Quentin Raimbourg, Leïla Tricot, Christiane Mousson, Aurélie Le Thuaut, Chantal Loirat, Véronique Frémeaux-Bacchi, Fadi Fakhouri, Marc Fila, Aurélie Hummel, David Ribes, Anne-Laure Sellier-Leclerc, Simon Ville, Claire Pouteil-Noble, Jean-Philippe Coindre, Moglie Le Quintrec, Eric Rondeau, Olivia Boyer, François Provôt, Djamal Djeddi, William Hanf, Yahsou Delmas, Ferielle Louillet, Annie Lahoche, Guillaume Favre, Valérie Châtelet, Emma Allain Launay, Claire Presne, Ariane Zaloszyc, Sophie Caillard, Stéphane Bally, Quentin Raimbourg, Leïla Tricot, Christiane Mousson, Aurélie Le Thuaut, Chantal Loirat, Véronique Frémeaux-Bacchi
Abstract
The optimal duration of eculizumab treatment in patients with atypical hemolytic uremic syndrome (aHUS) remains poorly defined. We conducted a prospective national multicenter open-label study to assess eculizumab discontinuation in children and adults with aHUS. Fifty-five patients (including 19 children) discontinued eculizumab (mean treatment duration, 16.5 months). Twenty-eight patients (51%) had rare variants in complement genes, mostly in MCP (n = 12; 22%), CFH (n = 6; 11%), and CFI (n = 6; 10%). At eculizumab discontinuation, 17 (30%) and 4 patients (7%) had stage 3 and 4 chronic kidney disease, respectively. During follow-up, 13 patients (23%; 6 children and 7 adults) experienced aHUS relapse. In multivariable analysis, female sex and presence of a rare variant in a complement gene were associated with an increased risk of aHUS relapse, whereas requirement for dialysis during a previous episode of acute aHUS was not. In addition, increased sC5b-9 plasma level at eculizumab discontinuation was associated with a higher risk of aHUS relapse in all patients and in the subset of carriers with a complement gene rare variant, both by log-rank test and in multivariable analysis. Of the 13 relapsing patients, all of whom restarted eculizumab, 11 regained their baseline renal function and 2 had a worsening of their preexisting chronic kidney disease, including 1 patient who progressed to end-stage renal disease. A strategy of eculizumab discontinuation in aHUS patients based on complement genetics is reasonable and safe. It improves the management and quality of life of a sizeable proportion of aHUS patients while reducing the cost of treatment. This trial was registered at www.clinicaltrials.gov as #NCT02574403.
© 2021 by The American Society of Hematology.
Source: PubMed