Cost-Effectiveness of Prophylaxis with Anti-Inhibitor Complex Concentrate in Patients with Hemophilia A and Inhibitors: Results From the Pro-FEIBA Study,

Prophylaxis with anti-inhibitor complex concentrate (AICC; FEIBA NF, Baxter Healthcare Corporation, Westlake Village, CA) has been shown to safely and significantly decrease the frequency of joint and other bleeding events in patients with severe hemophilia A and inhibitors. Nonetheless, AICC prophylaxis is an expensive therapeutic intervention, and evidence of its cost-effectiveness is needed to guide healthcare decision-making in this era of global economic downturn.

Hemophilia A patients >2 years of age with inhibitors and using bypassing therapy to treat bleeding were enrolled in a prospective, randomized, crossover study comparing 6 months of AICC infused prophylactically at a dose of 85U/kg ± 15% on 3 nonconsecutive days per week with 6 months of AICC used on-demand for bleeding episodes at a dose of 85 U/kg ± 15%. The 2 treatment periods were separated by a 3-month washout during which patients used on-demand therapy for bleeding. Clotting factor costs were quantitated in 2011 US dollars using the US price for US patients ($1.56 per unit) and the average price in Europe for European patients ($1.13 per unit).

Twenty-six subjects (median age 28.7 years; range, 2.8–62.8) completed both treatment periods and were evaluable per protocol for the cost-effectiveness analysis. The per-patient cost of 6 months of AICC prophylaxis was $493,633 compared with $205,549 for on-demand therapy. These totals were calculated by adding the per-patient cost of all clotting factors used during the prophylaxis period (AICC – $489,473 and recombinant activated factor VII [rFVIIa] – $4,160) and the on-demand period (AICC – $198,862473, rFVIIa – $6,272, and FVIII – $415). The incremental cost of AICC per bleed avoided during the prophylaxis period was $35,565, or $585/kg body weight for our somewhat older study population (mean body weight 60.8 kg). Sixteen of 26 subjects (62%) experienced a ≥50% reduction in bleeding events (“good responders”). For these subjects, the per-patient cost of 6 months of AICC prophylaxis was $499,453 as compared with $202,757 for on-demand therapy. The incremental cost-effectiveness ratio for the prophylaxis versus the on-demand period was $27,282 per bleeding event avoided ($449/kg body weight). In subjects with a <50% reduction in bleeding events, the per-patient cost of 6 months of AICC prophylaxis was $484,320 compared with $210,015 for on-demand therapy. The incremental cost-effectiveness ratio for the prophylaxis versus the on-demand period was $76,196 per bleeding event avoided.

The magnitude of the difference in factor costs during the prophylaxis and on-demand treatment periods was proportional to the corresponding difference in bleeding rate. During the on-demand period, factor cost was reduced by 58% compared with the prophylaxis period, whereas during the prophylaxis period, bleeding events were reduced by 62% compared with the on-demand period. The incremental cost effectiveness ratio was more favorable in good responders and is attributable to the marked difference in prophylactic efficacy. These costs do not reflect the potential benefits of prophylaxis, including fewer hospitalizations and days lost from work or school and prevention of long term complications, such as worsening joint disease and disability. After taking into consideration the bleeding rate, the cost of on-demand therapy is consistent with those previously reported in hemophilia A patients without inhibitors. The incremental cost of AICC per bleed avoided during the prophylaxis period suggests that prophylaxis may will be most cost-effective in those who experience a good response in bleed reduction and in children, who may also derive additional benefit through the prevention of joint disease and long-term disability.

Gringeri:Baxter: Speakers Bureau. Leissinger:Baxter: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.