Eculizumab discontinuation in children and adults with atypical hemolytic-uremic syndrome: a prospective multicenter study - Université de Montpellier Accéder directement au contenu
Article Dans Une Revue Blood Année : 2021

Eculizumab discontinuation in children and adults with atypical hemolytic-uremic syndrome: a prospective multicenter study

Simon Ville
Eric Rondeau
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Résumé

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.

Domaines

Hématologie

Dates et versions

hal-03222627 , version 1 (10-05-2021)

Identifiants

Citer

Fadi Fakhouri, Marc Fila, Aurélie Hummel, David Ribes, Anne-Laure Sellier-Leclerc, et al.. Eculizumab discontinuation in children and adults with atypical hemolytic-uremic syndrome: a prospective multicenter study. Blood, 2021, 137 (18), pp.2438-2449. ⟨10.1182/blood.2020009280⟩. ⟨hal-03222627⟩
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