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

Autor: Véronique Frémeaux-Bacchi, Christiane Mousson, Emma Allain Launay, David Ribes, François Provôt, Simon Ville, Aurélie Le Thuaut, Claire Presne, Anne-Laure Sellier-Leclerc, Aurélie Hummel, Ferielle Louillet, Leila Tricot, Marc Fila, Quentin Raimbourg, Stéphane Bally, Fadi Fakhouri, Eric Rondeau, Ariane Zaloszyc, Moglie Le Quintrec, Djamal Djeddi, William Hanf, Guillaume Favre, Annie Lahoche, Valérie Châtelet, Sophie Caillard, Chantal Loirat, Jean-Philippe Coindre, Claire Pouteil-Noble, Yahsou Delmas, Olivia Boyer
Přispěvatelé: Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service Néphrologie et transplantation rénale Adultes [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie - Immunologie Clinique [Toulouse], CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse]-PRES Université de Toulouse, Hospices Civils de Lyon (HCL), Centre Hospitalier Le Mans (CH Le Mans), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de référence des microangiopathies thrombotiques [CHU Saint-Antoine] (Cnr-mat), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Service de néphrologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie et Transplantation rénale [CHRU-lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Amiens-Picardie, Centre Hospitalier Alpes Léman (CHAL), Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Service de Néphrologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Universitaire de Nice (CHU Nice), Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de néphrologie et hémodialyse [CHU de Strasbourg], CHU Strasbourg, Service de néphrologie - dialyse [Centre hospitalier Métropole Savoie - Chambéry], Centre Hospitalier Métropole Savoie [Chambéry], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital Foch [Suresnes], Service de néphrologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), AP-HP Hôpital universitaire Robert-Debré [Paris], Service d'immunologie [HEGP, Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
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
Zdroj: Blood
Blood, American Society of Hematology, 2021, 137 (18), pp.2438-2449. ⟨10.1182/blood.2020009280⟩
ISSN: 0257-4403
0006-4971
1528-0020
DOI: 10.1182/blood.2020009280⟩
Popis: 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.
Databáze: OpenAIRE
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