Low‐dose immune tolerance induction for children with hemophilia A with poor‐risk high‐titer inhibitors: A pilot study in China

Background Immune tolerance induction ( ITI ) therapy is currently unaffordable in China. Management of hemophilia A children with high‐titer inhibitor is therefore a challenge. Aim To describe the ITI strategy using plasma‐derived factor VIII /von Willebrand factor concentrate (pd FVIII / VWF ) +/− immunosuppression and to report its efficacy in children with hemophilia A having poor‐risk status for ITI success. Methods A prospective pilot study on children with hemophilia A having poor‐risk status (all with at least inhibitor titer > 10 BU pre‐ ITI initiation). Patients received ~50 IU /kg FVIII every other day using domestic intermediate purity pd FVIII / VWF products, either alone or in combination with rituximab +/− prednisone. Results Sixteen patients with median age 2.9 (range, 2.2‐13.2) years and median pre‐ ITI inhibitor titer 30.7 (range, 10.4‐128) BU were enrolled. Analysis at median 14.7 (range, 12.4‐22.6) months’ follow‐up showed a total response rate of 87.5%. This included success (achieving inhibitor < 0.6 BU ) in 13 patients (81.3%) in a median of 8.8 (range, 3.2‐11.8) months, and partial success (achieving inhibitor < 5 BU but > 0.6 BU ) in 1 (6.3%). Compared to the pre‐ ITI period, the mean bleeds/month during ITI was 0.51 (64.0% reduction), and joint bleeds/month was 0.34 (64.3% reduction). This low‐dose ITI strategy cost less by 70% to 87% than that for the high‐dose FVIII regimen. No severe adverse events were observed. Conclusion This low‐dose ITI strategy of pd FVIII / VWF +/− immunosuppression achieved relatively satisfactory outcomes in children with hemophilia A inhibitor having poor‐risk status. This low‐dose regimen showed economic advantages and is therefore suitable for using in China. However, further study in a larger cohort with a longer follow‐up time is needed.