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Aims: Haemophilia is a rare genetic disease that hinders blood clotting. We aimed to review model-based cost-effectiveness analyses (CEAs) of haemophilia treatments, describe the sources of clinical evidence used by these CEAs, summarize the reported cost-effectiveness of different treatment strategies, and assess the quality and risk of bias., Methods: We conducted a systematic literature review of model-based CEAs of haemophilia treatments by searching databases, the Tufts Medical Center CEA registry, and grey literature. We summarized and qualitatively synthesized the approaches and results of the included CEAs, without a meta-analysis due the diversity of the studies., Results: 32 eligible studies were performed in 12 countries and reported 53 pairwise comparisons. Most studies analysed patients with haemophilia A rather than haemophilia B. Comparisons of prophylactic versus on-demand treatment indicated that prophylaxis may not be cost-effective, but there was no clear consensus. Emicizumab was generally cost-effective compared with clotting factor treatments and was always dominant for patients with inhibitors. Immune tolerance induction following a Malmö protocol was found to be cost-effective compared to bypassing agents, while there was no consensus for the other protocols. Gene therapies as well as treatment with extended half-life coagulation factors were always cost-effective over their comparators. Studies were highly heterogenous regarding their time horizons, model structures, the inclusion of bleeding-related mortality and quality-of-life impacts. This heterogeneity limited the comparability of the studies. 19 of the 32 included studies received industry funding, which may have biased their results., Limitations: It was not possible to perform a quantitative synthesis of the results due to the heterogeneity of the underlying studies., Conclusion: Differences in results between previous CEAs may have been driven by heterogeneity in modelling approaches, clinical input data, and potential funding biases. A more consistent evidence base and modelling approach would enhance the comparability between CEAs.

Objective: To evaluate the health system costs among patients with hemophilia A and B with and without inhibitors over 5 years., Methods: This was a retrospective, observational study utilizing medical and pharmacy electronic medical records and administrative encounters/claims data tracking US patients between 2006-2011. Patients with diagnosis codes for hemophilia A and B were identified. Patients with inhibitors were characterized by utilization of bypassing agents activated prothrombin complex concentrate or factor VIIa on two or more distinct dates. Severity was classified as mild, moderate, or severe based on laboratory tests of clotting factor., Results: There were 160 hemophilia A patients and 54 hemophilia B patients identified. From this group, seven were designated as patients with inhibitors (five with hemophilia A and two with hemophilia B). Hemophilia A patients without inhibitors reported 65 (41.9%) as being severe, 19 (12.3%) as moderate, and 71 (45.8%) as mild. Hemophilia B patients without inhibitors reported nine (17.3%) had severe, 13 (25.0%) had moderate, and 30 (57.7%) had mild hemophilia. All patients with inhibitors had been hospitalized in the previous 5 years compared to 64 (41.3%) with hemophilia A without inhibitors and 22 (42.3%) with hemophilia B without inhibitors. The median aggregate cost per year (including factor and health resource use) was $325,780 for patients with inhibitors compared to $98,334 for hemophilia A patients without inhibitors and $23,265 for hemophilia B patients without inhibitors., Conclusions: The results suggest that, while the frequency of inhibitors within the hemophilia cohort was low, there was a higher frequency of hospitalizations, and the associated median aggregate costs per year were 3-fold higher than those patients without inhibitors. In contrast, hemophilia B patients experience less severe disease and account for lower aggregate yearly costs compared to either patients with hemophilia A or patients with inhibitors.

Objective: Two bypassing agents, activated prothrombin complex concentrates (aPCC) and recombinant factor VIIa (rFVIIa), have shown similar efficacy and safety in the treatment of bleeding episodes in patients with hemophilia and inhibitors as demonstrated through the only two head-to-head clinical trials. Given the economic burden of bypassing treatment, it is crucial to have a valid estimate of cost effectiveness of alternative treatments. The aims of this study were to conduct a systematic review of published pharmacoeconomic literature on the cost-effectiveness of aPCC versus rFVIIa to treat mild-to-moderate bleeds in patients with hemophilia and inhibitors, with a focus on the model assumptions and their impact on results., Methods: An English language search was conducted for original economic studies comparing aPCC and rFVIIa published between 1995 and July 2010. Detailed information on sponsorship, study design, assumptions and their impact on results was collected for each study., Results: A total of 11 economic studies were included in the review. Nine studies assessed cost per bleeding episode (eight cost-minimization analysis (CMA) and one cost-effectiveness analysis (CEA)). Two studies were from longitudinal perspective. Studies on cost per bleeding episode were evaluated and systematically compared. All studies were from a third-party payer perspective. Most analyses, except one study, used a similar decision-tree model. The assumptions for all CMA studies were obtained from non-comparable single-armed trials or observational data. All studies were sponsored by the two competing manufacturers of rFVIIa (seven studies) and aPCC (two studies). The crucial parameter assumptions on treatment efficacy and dosing drove their reported findings. Eight of these nine studies favored their sponsor's product., Conclusion: With one exception, published economic studies tend to favor their sponsor's product primarily by assuming a higher efficacy and lower dosing for the sponsored agent, even though the two existing head-to-head clinical studies do not support superior efficacy for either product.