This amounts to $103 million of total subsidized. with high titer Cytosine inhibitors from an Iranian Ministry of Health perspective. == Methods == This study was based on the study of Knight et al, which evaluated the cost- Cytosine Cytosine effectiveness ratios of different treatments for hemophilia A with high-responding inhibitors. To adapt Knight et als results to the Iranian context, a few clinical parameters were diverse, and cost data were replaced with the corresponding Iranian estimates of resource use. The time horizon of the analysis was 10 years. One-way sensitivity analyses were performed, varying the cost of the clotting factor, the drug dose, and the administration frequency, to test the robustness of the analysis. == Results == Comparison of the incremental cost-effectiveness ratios between the three ITI protocols and the on-demand regimen with rFVIIa shows that all three ITI protocols dominate the on-demand regimen with rFVIIa. Between the ITI protocols the low-dose ITI protocol dominates both the Bonn ITI protocol and the Malm ITI protocol and would be the preferred ITI protocol. All of the three ITI protocols dominate the on-demand strategy, as they have both a lower average lifetime cost and higher quality-adjusted life-years (QALYs) gained. The cost per QALY gained for the Bonn ITI protocol compared with the Malm ITI protocol was $249,391.84. The cost per QALY gained for the Bonn ITI protocol compared with the low-dose ITI protocol was $842,307.69. == Conclusion == The results of data derived from our study suggest that the low-dose ITI protocol may be a less expensive and/or more cost-effective option compared with on-demand first-line treatment with rFVIIa. Keywords:cost-utility analysis, immune tolerance induction, on-demand, rFVIIa == Introduction == Hemophilia A is a bleeding disorder caused by a functional absence, or reduced levels, of factor VIII (FVIII). In the developed world, prophylaxis for hemophilia A uses infusions of virus-attenuated plasma-derived FVIII or recombinant (rFVIII) clotting factor replacement. Such treatment has substantially improved the quality of life (QoL) of persons with severe (FVIII > 1%) and moderate (FVIII 1%5%) hemophilia A by avoiding bleeding episodes and their long-term effects, particularly in the joints.1However, we are still grappling with issues of cost-effective care of the disease and its other complications. The most serious of these complications is the development of a neutralizing antibody, or inhibitor, to FVIII. In developed countries, where economic resources are available for high-cost products, the development of antibodies neutralizing the hemostatic effect Rabbit polyclonal to IWS1 of therapeutically administered clotting factor concentrates (inhibitors) is the key problem of treating hemophilia.2In the presence of an inhibitor, especially if at high titer, the standard safe and effective replacement treatment is hampered, and high rates of morbidity and mortality are reported.3In addition, this challenging treatment is associated with a very high economic burden.4,5At variance with other settings of chronic disease, costs of treatment in hemophilia are mainly related to direct costs of replacement clotting factor concentrates.5,6When patients with inhibitors are evaluated, these costs account for more than 98% of the strikingly high amount of medical and economic resources absorbed for their care.5 Development of inhibitors to transfused FVIII is currently the most severe and challenging complication of hemophilia treatment6and represents the highest economic burden for any chronic disease.7Inhibitors occur in up to one-third of patients with severe hemophilia A (FVIII, 1 u/dL).8The presence of an inhibitor complicates treatment and increases disease-related morbidity,9because it renders factor replacement ineffective.6,10Consequently, hemophiliacs with inhibitors, particularly those with high-titer inhibitors (over five Bethesda units), are at increased risk of uncontrollable Cytosine hemorrhage, damaging joint damage, and subsequent disability, although they are usually under treatment with bypassing agents.1013 To reduce these risks and improve QoL, immune tolerance induction (ITI), eg, the regular infusion of FVIII concentrates over a time period ranging from months to years, is usually attempted to overpower high responding (anamnesis) FVIII inhibitors of recent onset and restore normal factor pharmacokinetics.10,14,15 ITI is nowadays usually started in connection with, or early after development of, an inhibitor. The regimen used often comprises very high doses of factor concentrate, and the treatment course.
This amounts to $103 million of total subsidized
