The Immune Tolerance Induction Factor Utilizations and Costs for the Management of Male Hemophilia-a Patients Who Developed Inhibitors

Abstract

Background: Hemophilia-A is a chronic inherited bleeding disorder that results from deficiencies in factor VIII. Prophylactic replacement of coagulation factor VIII (FVIII) is the standard of care. However, about 20-30% of patients with severe hemophilia A may develop neutralizing antibodies (inhibitors) against the coagulation factor VIII. The Immune Tolerance Induction (ITI) method, consist in the regular infusion of variable FVIII doses to induce FVIII antigen-specific tolerance. It has proven the most effective inhibitor eradication treatment in patients with high-titer inhibitors. Current published studies reported wide range of findings on the factor usage and cost of treatment. The objective of this study is to describe the consumption, duration, and cost of ITI treatment in US healthcare settings. Methods: This retrospective analysis used MarketScan, an US health insurance claim database from January 2010 to September 2015. Eligible patients were: male hemophilia-A inhibitor patients who received ITI treatment. ITI treatment was identified as patients who tested Bethesda/Nijmegen assays between 30 days prior to an ITI index date and the end of study period; and used high dose of factor therapy (>3 times of the median IU factors dispensed for patients in the same age group for more than 5 consecutive months, allowing one month gap). Conclusion of ITI treatment was defined as when the amount of IU dispensed has fallen under 1.5 times of the median amount dispensed, or remaining in ITI treatment at the end of study period. Patients, who used by-pass agents to treat bleeding without undergoing ITI, were excluded. The total cost of ITI treatment was focused only on the cost of factor therapy. The treatment duration, cost, and IU consumption were further stratified by age groups and specific factor therapies. Results: Of the 2,302 hemophilia-A patients, 231 inhibitor patients were identified. A total of 72 patients used high dose short-acting factors for ITI treatment. No patient receiving long-acting factor was captured in the inhibitor population. Table 1 lists the patient counts, duration and cost of ITI treatment by age groups. Higher percentages of younger patient groups developed inhibitor compared with older age groups. About 14% of hemophilia-A patients aged 7 and under had ITI treatment. The older groups (aged 16 and older) had higher total costs as they required higher IU of factor therapy. The average duration of ITI treatment was 18.7 months, and the average total cost was $1,463,668 per patient regardless of the type of short acting factor therapy used. Conclusions: This US health insurance claim database study reflects that the current utilization of short acting factor for ITI treatment is associated with high cost burden. Products that decrease or eliminate inhibitor formation should be developed. Disclosures Su: Novartis Pharmaceuticals Corporation: Employment; Biogen: Employment, Equity Ownership. Zhou:Biogen: Employment, Equity Ownership. Buckley:Biogen: Employment, Equity Ownership. Rising:Biogen: Employment, Equity Ownership. Hou:Biogen: Employment, Equity Ownership. Jain:Biogen: Employment, Equity Ownership.

Recombinant factor VIII Fc fusion protein for immune tolerance induction in patients with severe haemophilia A with inhibitors—A retrospective analysis

“…What most impacts on the cost of ITI is its long duration. A US claims data analysis indicated that the real‐world average duration of ITI with conventional FVIII products was 18.7 months . The data presented in our study indicate that rFVIIIFc may offer a more rapid time to tolerization; this could in turn be associated with a potential decrease in long‐term bypassing agent use and improvements in the excessive financial burden associated with ITI.…”

“…The main limitations of ITI with conventional factor replacement therapies are the need for frequent factor infusions, which in most young children necessitates indwelling CVAD; the decreased quality of life while on ITI; and enormous healthcare utilization costs given the high doses of factor required . All of these are compounded by the extended duration of treatment needed to achieve tolerization.…”

“…Immune tolerance induction is a substantial economic burden in the healthcare utilization system, with high costs for both the FVIII and bypassing agents used. One study estimated that the average monthly costs of ITI were $103,000 ($78,000 for standard half‐life FVIII and $25,000 for bypassing agents) or $1.2 million per patient per year . What most impacts on the cost of ITI is its long duration.…”

Real‐world analysis of patients with haemophilia A and haemophilia A carriers in the United States: Demographics, clinical characteristics and costs

“…Patients with ≥2 claims at least 30 days apart for haemophilia B, other bleeding disorders, interrupted plan enrolment (defined by a gap in medical and pharmacy benefits of ≥45 days) or claims for HACs in males without any claims for HA were excluded. Patients who developed FVIII inhibitors (identified from coagulation factor VIIa/anti‐inhibitor coagulant claims) and/or received immune tolerance induction therapy (identified as described previously 15 ) were also excluded.…”

“…13 The objective of this study was to describe patient characteristics, billed annualised bleed rates (ABR b ), HCRU and costs in US clinical practice using administrative claims data in male patients with HA (MHAs), FHAs and HACs. Patients who developed FVIII inhibitors (identified from coagulation factor VIIa/anti-inhibitor coagulant claims) and/or received immune tolerance induction therapy (identified as described previously 15 ) were also excluded.…”