Bleeding in patients with hemophilia who have inhibitors: Modeling US medical system utilization and cost avoidance between recombinant factor VIIa products with different clinical dosing requirements.

BACKGROUND: A mainstay of treatment in patients with hemophilia with inhibitors (PWIs) is the use of a recombinant factor VIIa (rFVIIa) bypassing agent. A new rFVIIa product may allow reduced rFVIIa utilization for on-demand treatment of bleeding episodes (BEs). OBJECTIVE: A decision analytic health economic model was developed to compare the utilization and consequent need for bleed-related clinical encounters of 2 rFVIIa products, with the International Nomenclature Name of eptacog alfa (EA) and eptacog beta (EB). METHODS: This study uses recent, peer-reviewed, and published data from clinical trials with similar endpoints for 1 million insured male lives in the United States. rFVIIa product utilization was modeled in hemophilia (A and B) PWI for on-demand treatment of BEs with rFVIIa treatment. Estimated annual BE rates were modeled to include prophylaxis and on-demand management. The clinical encounter avoidance estimates are based on refractory bleeding through 24 hours. RESULTS: In a cohort of 1 million insured, 5-6 patients with hemophilia A or B with inhibitors annually receive on-demand treatment for a total of 59 mild/moderate BEs. The model suggests that EB requires less unit utilization per BE (13,125 µg and 17,850 µg for the 75µg/kg and 225µg/kg dose regimens, respectively) than EA 90 µg/kg dosing (20,178µg), with wholesale acquisition costs expanding the difference. Further, both EB initial dose regimens would permit decreased total nonmedication health plan spending for the acute treatment of BEs by reducing the need for clinical encounters arising from BEs that fail to respond within 24 hours. CONCLUSIONS: With reduced infusion requirements, the model consistently shows that EB could generate lower insured-cohort drug utilization, as well as reduce costly clinical encounters by keeping mild and moderate BEs amenable to home bypassing agent management. DISCLOSURES: The article was funded by HEMA Biologic, LLC. The authors approved all content and results in this article without being subject to sponsor censorship. Mr Jensen, Mr Cyr, and Ms Hathway are employees of PRECISIONheor, which provides consulting services to the pharmaceutical industry, including HEMA Biologics, LLC. Dr Batt is an advisor to PRECISIONheor. Dr Alexander is a former employee of HEMA Biologics, LLC, and provides consulting services to the pharmaceutical industry.

Thromboembolism, Bleeding, and Mortality Incidence of Direct Oral Anticoagulants Versus Warfarin Postbariatric Surgery.

BACKGROUND: There is no randomized controlled trial comparing direct oral anticoagulants (DOACs) and warfarin following bariatric surgery to date. The mortality, thromboembolism, and bleeding risk of DOACs in comparison with warfarin following bariatric surgery remains unclear. We aimed to provide a clinical comparison between DOACs and warfarin for these 3 prespecified outcomes. METHODS: A systematic literature search was performed on November 10, 2019, using PubMed, Embase, clinicaltrial.gov, and Cochrane databases. Studies with adult patients who were on either warfarin or DOACs following bariatric surgery and reported the incidence of thromboembolism, bleeding, or mortality were included. Pooled incidence for these prespecified outcomes and its 95% confidence interval (CI) were calculated for each drug separately using the random-effects model, along with a nonadjusted P value comparing the 2 subgroups. RESULTS: A total of 11 studies (805 patients) were included. Comparing DOACs to warfarin, the following pooled incidences were observed for mortality (DOACs: 3.0%; 95% CI 0.4%-18.6% versus warfarin: 1.5%; 95% CI 0.8%-2.9%; P value comparing the 2 subgroups = .38), thromboembolism (DOACs: 4.9%; 95% CI 1%-21.1% versus warfarin: 1.5%; 95% CI 0.8%-2.9%; P value = .18), and bleeding (DOACs: 3.9%; 95% CI 0.7%-18.2% versus warfarin: 11.3%; 95% CI 5.7%-21.4%; P value = .23). CONCLUSION: The results of our meta-analysis remain hypothesis-generating, providing rationale for future randomized controlled trial design or well-designed comparative observational studies. Currently, it does not support the change in the current recommendation from warfarin to DOACs following bariatric surgery.