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

Abstract

The optimal duration of eculizumab treatment in patients with atypical haemolytic uremic syndrome (aHUS) remains poorly defined. We conducted a prospective national multicentric open-label study in order to assess eculizumab discontinuation in children and adults with aHUS. Fifty-five patients (including 19 children) discontinued eculizumab (mean duration of treatment, 16.5 months). Twenty-eight (51%) patients had complement gene rare variants, mostly in MCP (n= 12, 22%), CFH (n= 6, 11%) and CFI (n=6, 10%) genes. At eculizumab discontinuation, 17 (30%) and 4 (7%) patients had chronic kidney disease stage 3 and 4, respectively. During follow-up, 13 (23%) patients (6 children and 7 adults) experienced aHUS relapse. In multivariable analysis, female gender and the presence of a rare complement gene variant were associated with an increased risk of aHUS relapse, whereas requirement for dialysis during previous episodes of acute aHUS was not. In addition, an increased soluble C5b-9 plasma level at eculizumab discontinuation was associated with a higher risk of aHUS relapse in all patients and in the subset of carriers of complement gene rare variants, in log rank test and in multivariable analysis. Among the 13 relapsing patients, who were all restarted on eculizumab, 11 regained their baseline renal function and two had a worsening of their pre-existing chronic kidney disease, including one 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. Trail registration number: NCT02574403.

Thrombotic microangiopathy after kidney transplantation: Analysis of the Brazilian Atypical Hemolytic Uremic Syndrome cohort

“…This strategy may benefit the access of eculizumab without resulting in an excessive cost to the public health system, especially in low-income countries. However, to date, the best strategy to definided eculizumab interruption was based on genetic analysis [ 25 , 34 ]. The cost-effectiveness of accessing eculizumab for kidney transplant patients should be based on genetic analysis, thus, it is necessary to include the genetic profile for patients with suspicion for aHUS.…”

“…In those classified at high to moderate risk according to KDIGO 2017 [ 1 ] we strongly consider prophylaxis. As the opposite, we consider discontinuing the use in those without identified genetic variants, as well as the saving of 32 million euros realized by the STOPECU study [ 34 ] after the discontinuation of 55 patients with an average of 24 months of follow-up.…”

Rare Presentation of Atypical Hemolytic Uremic Syndrome in an Adult

“…In patients with no complement gene variants, the risk of aHUS relapse was less than 5% but was significantly higher in carriers of complement gene variants reaching 50%. Time to relapse ranged from 1 to 22 months and was primarily precipitated by infections [ 13 ].…”

Pregnancy-related atypical hemolytic uremic syndrome with renal, cardiac and obstetric complications and a satisfactory recovery: a case report

“…The low relapse rates may be related to the low complement factor H mutations in the patient cohorts [6]. Fakhouri et al reported in their prospective study that discontinuation of eculizumab is reasonable and safe, in accordance with the complement mutation results of the patients [7]. The presence of complement gene abnormalities is a risk for aHUS relapse after anti-C5 treatment discontinuation, including in P-aHUS patients.…”