Efficacy, Safety and Economic Evaluation of Recombinant Activated Factor VII (rFVIIa) in the Management of Mild and Moderate Bleedings in Haemophilia Patients with Inhibitors in Brazil.

Abstract Background: In Brazil treatment option for mild and moderate bleeding episodes in high responding inhibitors patients is Activated Prothrombin Complex Concentrates (aPCC). rFVIIa is only used as second line therapy in severe bleeds or for elective surgeries. Objectives: To evaluate efficacy, safety and economic impact of rFVIIa as first line treatment for mild and moderate bleeds in high responding inhibitors patients. Methods: Efficacy and safety of rFVIIa were based on a prospective evaluation of 22 mild and moderate bleeds treated between July 2004 and February 2006. Resource utilization was based on retrospective and prospective analysis of 66 bleeding episodes treated in less than 12 hours of beginning of symptoms with rFVIIa and aPCC during the period of August 2002 to February 2006. Clinical outcomes were derived from the analysis of the data obtained from the review of patients’ records and prospective evaluation. Results were validated through a consensus of four Brazilian hematologists and a decision analyis model was constructed to assess total direct health care costs using the software package DATATM 3.5 (TreeAge Software, Willianstown - MA, USA). Results: From July 2004 to February 2006, nine mild (40.9%) and thirteen moderate (59.1%) bleeding episodes were prospectively treated with rFVIIa. All bleedings resolved with 1–4 doses (average 2.05). Haemostasis was maintained in 18/22 bleedings for five days (81.8%). No adverse events were reported. From August 2002 to May 2004 other 44 mild and moderate bleeding episodes were retrospectively reviewed for the economic evaluation, 33 with aPCC and 11 with rFVIIa. Overall, mean time to bleed resolution in hours, mean number of doses and efficacy rate were 56.8, 3.7, 63.6% and 2.7, 1.6 and 100% for aPCC and rFVIIa, respectively. Using the decision analysis model constructed, total direct costs were US$ 12,134 and US$ 7,307 for aPCC and rFVIIa, respectively. When sensitivity analysis was carried out using first-line efficacy rates based on literature data (aPCC: 80% and rFVIIa: 92%)1,2, the total process costs were lower for rFVIIa (US$ 7,850) as compared with aPCC (US$ 10,328) as initial treatment. Conclusion: On the basis of the results of this study it could be concluded that the use of rFVIIa as first-line treatment for mild and moderate bleeds in haemophilia patients with inhibitors in Brazil is not only justified on a clinical basis but also from and economic point of view.