Cyclophosphamide vs rituximab for eradicating inhibitors in acquired hemophilia A: A randomized trial in 108 patients.

Acquired hemophilia Cyclophosphamide Randomized trial Rituximab

Journal

Thrombosis research
ISSN: 1879-2472
Titre abrégé: Thromb Res
Pays: United States
ID NLM: 0326377

Informations de publication

Date de publication:
15 Mar 2024
Historique:
received: 07 11 2023
revised: 19 02 2024
accepted: 07 03 2024
medline: 1 4 2024
pubmed: 1 4 2024
entrez: 31 3 2024
Statut: aheadofprint

Résumé

Acquired hemophilia A (AHA) is a rare autoimmune disorder due to autoantibodies against Factor VIII, with a high mortality risk. Treatments aim to control bleeding and eradicate antibodies by immunosuppression. International recommendations rely on registers and international expert panels. CREHA, an open-label randomized trial, compared the efficacy and safety of cyclophosphamide and rituximab in association with steroids in patients with newly diagnosed AHA. Participants were treated with 1 mg/kg prednisone daily and randomly assigned to receive either 1.5-2 mg/kg/day cyclophosphamide orally for 6 weeks, or 375 mg/m Recruitment was interrupted because of new treatment recommendations after 108 patients included (58 cyclophosphamide, 50 rituximab). After 18 months, 39 cyclophosphamide patients (67.2 %) and 31 rituximab patients (62.0 %) were in complete remission (OR 1.26; 95 % CI, 0.57 to 2.78). In the poor prognosis group (FVIII < 1 IU/dL, inhibitor titer > 20 BU mL Cyclophosphamide and rituximab showed similar efficacy and safety. As first line, cyclophosphamide seems preferable, especially in poor prognosis patients, as administered orally and less expensive. French Ministry of Health. gov number: NCT01808911.

Sections du résumé

BACKGROUND BACKGROUND
Acquired hemophilia A (AHA) is a rare autoimmune disorder due to autoantibodies against Factor VIII, with a high mortality risk. Treatments aim to control bleeding and eradicate antibodies by immunosuppression. International recommendations rely on registers and international expert panels.
METHODS METHODS
CREHA, an open-label randomized trial, compared the efficacy and safety of cyclophosphamide and rituximab in association with steroids in patients with newly diagnosed AHA. Participants were treated with 1 mg/kg prednisone daily and randomly assigned to receive either 1.5-2 mg/kg/day cyclophosphamide orally for 6 weeks, or 375 mg/m
RESULTS RESULTS
Recruitment was interrupted because of new treatment recommendations after 108 patients included (58 cyclophosphamide, 50 rituximab). After 18 months, 39 cyclophosphamide patients (67.2 %) and 31 rituximab patients (62.0 %) were in complete remission (OR 1.26; 95 % CI, 0.57 to 2.78). In the poor prognosis group (FVIII < 1 IU/dL, inhibitor titer > 20 BU mL
CONCLUSION CONCLUSIONS
Cyclophosphamide and rituximab showed similar efficacy and safety. As first line, cyclophosphamide seems preferable, especially in poor prognosis patients, as administered orally and less expensive.
FUNDING BACKGROUND
French Ministry of Health.
CLINICALTRIALS RESULTS
gov number: NCT01808911.

Identifiants

pubmed: 38555718
pii: S0049-3848(24)00083-5
doi: 10.1016/j.thromres.2024.03.012
pii:
doi:

Banques de données

ClinicalTrials.gov
['NCT01808911']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

79-87

Informations de copyright

Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

H Lévesque (H)

Normandie Univ, UNIROUEN, U 1096, CHU Rouen, Department of Internal Medicine, F-76000 Rouen, France. Electronic address: Herve.Levesque@chu-rouen.fr.

J F Viallard (JF)

Service de Médecine Interne et Maladies Infectieuses Hôpital Haut-Lévêque, CHU Bordeaux, 5 avenue de Magellan, 33604 Pessac, France.

E Houivet (E)

Department of Biostatistics, CHU Rouen, F-76031 Rouen, France.

B Bonnotte (B)

Service de médecine interne et immunologie clinique, CHU Dijon-Bourgogne, Université de Dijon, F-21079 Dijon, France.

S Voisin (S)

Department of Internal Medicine, CHU Toulouse, F-31059 Toulouse. France.

V Le Cam-Duchez (V)

Normandie Univ, UNIROUEN, Hématologie biologique, F-76031 Rouen, France.

F Maillot (F)

Département de Médecine Interne et immunologie clinique, CHRU Tours, Université de Tours, F-37044 Tours, France.

M Lambert (M)

CHU Lille, Département de Médecine Interne et d'Immunologie Clinique, Centre National de Référence Maladies Systémiques et Auto-immunes Rares Nord et Nord-Ouest de France (CeRAINO), European Reerence Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNECT), F-59000 Lille, France.

E Liozon (E)

Department of Internal Medicine, Dupuytren Hospital, F-87000 Limoges, France.

B Hervier (B)

Service de Médecine Interne, Hôpital Saint-Louis, APHP, 75010 Paris & INSERM UMR-S 976, Human Immunology, Pathophysiology, Immunotherapy, Saint-Louis Research Institute, F-75000 Paris, France.

O Fain (O)

Sorbonne Université, APHP, Service de Médecine Interne-DMU i3, Hôpital Saint-Antoine, Paris F-75000, France.

B Guillet (B)

Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR-S 1085, F-35000 Rennes, France.

J Schmidt (J)

Department of Internal Medicine, Amiens University Hospital, F-80000 Amiens, France.

L E Luca (LE)

Department of Internal Medicine, Poitiers University Hospital, F-86000 Poitiers, France.

M Ebbo (M)

Service de Médecine Interne, Hôpital La Timone, CHU Marseille, Aix-Marseille Université, F-13000 Marseille, France.

N Ferreira-Maldent (N)

Département de Médecine Interne et immunologie clinique, CHRU Tours, Université de Tours, F-37044 Tours, France.

A Babuty (A)

Service d'Hématologie Biologique, CRC-MHC, CHU de Nantes, Nantes Cedex 1, France.

L Sailler (L)

Department of Internal Medicine, CHU Toulouse, F-31059 Toulouse. France.

P Duffau (P)

Service de Médecine Interne-Immunologie Clinique Hôpital Saint-André, CHU Bordeaux, 1 rue Jean Burguet, 33075 Bordeaux, France.

V Barbay (V)

Normandie Univ, UNIROUEN, Hématologie biologique, F-76031 Rouen, France.

S Audia (S)

Service de médecine interne et immunologie clinique, CHU Dijon-Bourgogne, Université de Dijon, F-21079 Dijon, France.

J Benichou (J)

Department of Biostatistics, CHU Rouen and CESP UMR 1018, University of Rouen and University Paris-Saclay, F-76031 Rouen, France.

J Graveleau (J)

Nantes Université, CHU Nantes, Service de Médecine Interne, Nantes, France.

Y Benhamou (Y)

Normandie Univ, UNIROUEN, U 1096, CHU Rouen, Department of Internal Medicine, F-76000 Rouen, France.

Classifications MeSH