Rituximab and immune tolerance in severe hemophilia A: a consecutive national cohort.
SUMMARY BACKGROUND AND OBJECTIVES: he management of patients with severe hemophilia A and inhibitors to factor VIII (FVIII) resistant to standard immune tolerance is challenging. There have been recent case reports of the successful use of rituximab in up to 57% of patients as part of rescue immune tolerance regimens. Because case reports and small series are prone to the potential bias of reporting good outcomes and relatively short follow up, a consecutive cohort of all patients treated in the UK with prolonged follow up was analyzed.


METHODS
A national survey of all Comprehensive Care Haemophilia Center in the UK.


RESULTS
A total of 15 patients were reported of whom six (40%) achieved a negative inhibitor titer by Bethesda assay. Durable responses were unusual, observed in only 14% of cases. Clinically significant responses with either a negative inhibitor or an inhibitor titer < 5 BU mL(-1) and no spontaneous bleeding with FVIII replacement were observed in seven (47%) cases. Concomitant use of FVIII appeared to be important. Of the 12 patients treated with rituximab and FVIII, six (50%) achieved a negative inhibitor titer and seven (58%) had a clinically beneficial response. None of the three patients treated without FVIII responded.


CONCLUSIONS
These data suggest that the use of rituximab combined with FVIII is a potentially useful treatment for patients with inhibitors resistant to standard immune tolerance, although sustained inhibitor eradication is uncommon.
Collins
P W
PW
School of Medicine, Cardiff University, University Hospital of Wales, Cardiff, UK. peter.collins@cardiffandvale.wales.nhs.uk
Mathias
M
M
Hanley
J
J
Keeling
D
D
Keenan
R
R
Laffan
M
M
Perry
D
D
Liesner
R
R