Eculizumab discontinuation in children and adults with atypical hemolytic-uremic syndrome: a prospective multicenter study
Fadi Fakhouri
(1, 2)
,
Marc Fila
(3)
,
Aurélie Hummel
(4)
,
David Ribes
(5)
,
Anne-Laure Sellier-Leclerc
(6)
,
Simon Ville
(1)
,
Claire Pouteil-Noble
(6)
,
Jean-Philippe Coindre
(7)
,
Moglie Le Quintrec
(3, 8)
,
Eric Rondeau
(9)
,
Olivia Boyer
(10, 11, 12)
,
François Provôt
(13)
,
Djamal Djeddi
(14)
,
William Hanf
(15)
,
Yahsou Delmas
(16)
,
Ferielle Louillet
(17)
,
Annie Lahoche
(13)
,
Guillaume Favre
(18)
,
Valérie Châtelet
(19)
,
Emma Allain Launay
(1)
,
Claire Presne
(14)
,
Ariane Zaloszyc
(20)
,
Sophie Caillard
(20)
,
Stéphane Bally
(21)
,
Quentin Raimbourg
(22)
,
Leïla Tricot
(23)
,
Christiane Mousson
(24)
,
Aurélie Le Thuaut
(1)
,
Chantal Loirat
(25)
,
Véronique Frémeaux-Bacchi
(26)
1
CHU Nantes -
Centre Hospitalier Universitaire de Nantes
2 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
3 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
4 Service Néphrologie et transplantation rénale Adultes [CHU Necker]
5 Service de Néphrologie - Immunologie Clinique [Toulouse]
6 HCL - Hospices Civils de Lyon
7 Centre Hospitalier Le Mans (CH Le Mans)
8 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
9 CHU Tenon [AP-HP]
10 CHU Saint-Antoine [AP-HP]
11 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
12 Service de néphrologie pédiatrique [CHU Necker]
13 Service de Néphrologie et Transplantation rénale [CHRU-lille]
14 CHU Amiens-Picardie
15 CHAL - Centre Hospitalier Alpes Léman
16 Service de Néphrologie-transplantation-dialyse [Bordeaux]
17 Service de Néphrologie [Rouen]
18 CHU Nice - Centre Hospitalier Universitaire de Nice
19 Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen]
20 Service de néphrologie et hémodialyse [CHU de Strasbourg]
21 Service de néphrologie - dialyse [Centre hospitalier Métropole Savoie - Chambéry]
22 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
23 Hôpital Foch [Suresnes]
24 Service de néphrologie (CHU de Dijon)
25 AP-HP Hôpital universitaire Robert-Debré [Paris]
26 Service d'immunologie [HEGP, Paris]
2 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
3 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
4 Service Néphrologie et transplantation rénale Adultes [CHU Necker]
5 Service de Néphrologie - Immunologie Clinique [Toulouse]
6 HCL - Hospices Civils de Lyon
7 Centre Hospitalier Le Mans (CH Le Mans)
8 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
9 CHU Tenon [AP-HP]
10 CHU Saint-Antoine [AP-HP]
11 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
12 Service de néphrologie pédiatrique [CHU Necker]
13 Service de Néphrologie et Transplantation rénale [CHRU-lille]
14 CHU Amiens-Picardie
15 CHAL - Centre Hospitalier Alpes Léman
16 Service de Néphrologie-transplantation-dialyse [Bordeaux]
17 Service de Néphrologie [Rouen]
18 CHU Nice - Centre Hospitalier Universitaire de Nice
19 Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen]
20 Service de néphrologie et hémodialyse [CHU de Strasbourg]
21 Service de néphrologie - dialyse [Centre hospitalier Métropole Savoie - Chambéry]
22 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
23 Hôpital Foch [Suresnes]
24 Service de néphrologie (CHU de Dijon)
25 AP-HP Hôpital universitaire Robert-Debré [Paris]
26 Service d'immunologie [HEGP, Paris]
Simon Ville
- Fonction : Auteur
- PersonId : 795314
- ORCID : 0000-0003-0618-6187
Olivia Boyer
- Fonction : Auteur
- PersonId : 889775
- ORCID : 0000-0002-3957-1359
- IdRef : 11556134X
Christiane Mousson
- Fonction : Auteur
- PersonId : 762476
- ORCID : 0000-0003-0861-2506
Véronique Frémeaux-Bacchi
- Fonction : Auteur
- PersonId : 761449
- ORCID : 0000-0002-4865-8528
- IdRef : 081825781
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.