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

Blood. 2021 May 6;137(18):2438-2449. doi: 10.1182/blood.2020009280.


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 as #NCT02574403.

Publication types

  • Clinical Trial, Phase IV
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Atypical Hemolytic Uremic Syndrome / drug therapy*
  • Atypical Hemolytic Uremic Syndrome / metabolism
  • Atypical Hemolytic Uremic Syndrome / pathology
  • Child
  • Child, Preschool
  • Complement Inactivating Agents / therapeutic use*
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Prognosis
  • Prospective Studies
  • Survival Rate
  • Withholding Treatment / statistics & numerical data*
  • Young Adult


  • Antibodies, Monoclonal, Humanized
  • Complement Inactivating Agents
  • eculizumab

Associated data