Immune Tolerance Therapy in Children with FVIII Inhibitors

Abstract 4656

In up to 40% of cases, Hemophilia A treatment is complicated by the development of FVIII inhibitors, rendering the patient resistant to replacement therapy and increasing the risk of unmanageable bleeding, particularly arthropathy and disability. Presence of an inhibitor dramatically increases overall treatment costs 3–5 fold. Bleeding episodes in inhibitor patients require hospitalisation and bypassing agents such as rFVIIa. Immune tolerance (ITI) therapy, involving repetitive and persistent treatment with FVIII replacement is the only proven strategy for inhibitor eradication.

Since 2006, 30 children with inhibitors and poor-prognosis for ITI success have been treated with octanate^® for ITI at seven Russian haemophilia treatment centers in the frame of the ongoing Observational Immune Tolerance Induction (ObsITI) study. The median age was 5 years.

The objective of this study was to evaluate the progress of prospective ITI with octanate^® in children with inhibitors and a poor-prognosis for ITI success. In addition, joint status using a new musculoskeletal assessment tool before, during or after ITI was evaluated. A cost-of-care analysis to assess the consumption of octanate® in ITI in comparison with rFVIIa and to quantify the average direct medical costs for the treatment of young patients with FVIII inhibitors was also performed.

Despite the stringent success criteria, octanate^®, along with the high-dose Bonn protocol, has led to a complete success rate of about 80% in children with inhibitors and poor prognostic factor for ITI success.

Successful tolerisation with octanate^® allows resumption of fully effective replacement treatment with a consequent improvement in the patients’ musculoskeletal outcome and estimated savings over 5 years of € 600000. In addition, breakpoint analyses estimated that the number of years after which ITI with octanate^® pays off compared with on-demand treatment with rFVIIa is 1.4 years.

In summary, octanate^® is safe, well tolerated and effective in the induction of immune tolerance, even in poor-prognosis patients. The comparative cost-of-care analysis will help to optimize the therapy for the inhibitor patient and to ensure an effective allocation of financial resources.