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Randomized Controlled Trial
. 2024 May:237:79-87.
doi: 10.1016/j.thromres.2024.03.012. Epub 2024 Mar 15.

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

H Lévesque  1 , J F Viallard  2 , E Houivet  3 , B Bonnotte  4 , S Voisin  5 , V Le Cam-Duchez  6 , F Maillot  7 , M Lambert  8 , E Liozon  9 , B Hervier  10 , O Fain  11 , B Guillet  12 , J Schmidt  13 , L E Luca  14 , M Ebbo  15 , N Ferreira-Maldent  7 , A Babuty  16 , L Sailler  5 , P Duffau  17 , V Barbay  6 , S Audia  4 , J Benichou  18 , J Graveleau  19 , Y Benhamou  20 ; CREHA Study investigators on behalf the scientific committee of the “Société Nationale Française de Médecine Interne” (SNFMI – French National Society of Internal Medicine)
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Free article
Randomized Controlled Trial

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

H Lévesque et al. Thromb Res. 2024 May.
Free article

Abstract

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/m2 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.

Keywords: Acquired hemophilia; Cyclophosphamide; Randomized trial; Rituximab.

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Conflict of interest statement

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.

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