Cyclophosphamide vs rituximab for eradicating inhibitors in acquired hemophilia A: A randomized trial in 108 patients - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Thrombosis Research Année : 2024

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

J. F. Viallard
  • Fonction : Auteur
E Houivet
  • Fonction : Auteur
S Voisin
  • Fonction : Auteur
E Liozon
  • Fonction : Auteur
O Fain
J Schmidt
  • Fonction : Auteur
M Ebbo
  • Fonction : Auteur
A Babuty
  • Fonction : Auteur
L Sailler
  • Fonction : Auteur
P Duffau
  • Fonction : Auteur

Résumé

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: 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(2) rituximab once weekly for 4 weeks. The primary endpoint was complete remission over 18 months. Secondary endpoints included time to achieve complete remission, relapse occurrence, mortality, infections and bleeding, and severe adverse events. 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(-1)), significantly more remissions were observed with cyclophosphamide (22 patients, 78.6 %) than with rituximab (12 patients, 48.0 %; p = 0.02). Relapse rates, deaths, severe infections, and bleeding were similar in the 2 groups. In patients with severe infection, cumulative doses of steroids were significantly higher than in patients without infection (p = 0.03). CONCLUSION: 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: French Ministry of Health. CLINICALTRIALS: gov number: NCT01808911.

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hal-04534270 , version 1 (05-04-2024)

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H Lévesque, J. F. Viallard, E Houivet, B Bonnotte, S Voisin, et al.. Cyclophosphamide vs rituximab for eradicating inhibitors in acquired hemophilia A: A randomized trial in 108 patients. Thrombosis Research, 2024, 237, pp.79-87. ⟨10.1016/j.thromres.2024.03.012⟩. ⟨hal-04534270⟩
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