Rituximab in the treatment of high responding inhibitors in severe haemophilia A

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Abstract
Summary.  The development of antibodies to factor VIII (FVIII) in severely affected haemophilia A patients is a serious complication associated with increased morbidity and mortality. Bypassing agents are used to treat acute bleeding episodes; however, elimination of the inhibitors can only be achieved with immune tolerance therapy (ITT) in 60–80% of cases. High responding (HR) inhibitors are more likely to respond to ITT if the titre is decreased to −2, once weekly for four consecutive weeks. Both patients showed a partial response to rituximab reducing the inhibitor titre to <5 BU, thus facilitating ITT initiation; however, only the older patient eradicated the inhibitor within 21 days after application of ITT. The second patient, despite depletion of B cells, did not respond to ITT. No long‐term side effects have been observed in both patients for a follow‐up period of 20 and 18 months respectively. In conclusion, rituximab appears to be an alternative effective therapy to rapidly reduce or eliminate the inhibitor in selected cases of severely affected haemophiliacs before further proceeding to ITT. However, the dose and appropriate schedule, as well as long‐term side effects need further investigation.