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Eculizumab discontinuation in children and adults with atypical hemolytic-uremic syndrome: a prospective multicenter study
- Source :
- Blood, Blood, American Society of Hematology, 2021, 137 (18), pp.2438-2449. ⟨10.1182/blood.2020009280⟩
- Publication Year :
- 2021
- Publisher :
- HAL CCSD, 2021.
-
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.
- Subjects :
- Adult
Male
medicine.medical_specialty
Adolescent
medicine.medical_treatment
Immunology
030232 urology & nephrology
Renal function
Disease
030204 cardiovascular system & hematology
Antibodies, Monoclonal, Humanized
urologic and male genital diseases
Biochemistry
Young Adult
03 medical and health sciences
0302 clinical medicine
Quality of life
Internal medicine
Atypical hemolytic uremic syndrome
medicine
Humans
Prospective Studies
Child
Dialysis
Atypical Hemolytic Uremic Syndrome
business.industry
Infant, Newborn
Infant
[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology
Cell Biology
Hematology
Eculizumab
Prognosis
medicine.disease
3. Good health
Discontinuation
Survival Rate
Complement Inactivating Agents
Withholding Treatment
Child, Preschool
Female
business
BLOOD Commentary
Follow-Up Studies
Kidney disease
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 02574403, 00064971, and 15280020
- Database :
- OpenAIRE
- Journal :
- Blood, Blood, American Society of Hematology, 2021, 137 (18), pp.2438-2449. ⟨10.1182/blood.2020009280⟩
- Accession number :
- edsair.doi.dedup.....105ee1348fd54e8d802db81dde74df0a