aPCC vs. rFVIIa for the treatment of bleeding in patients with acquired haemophilia – a cost‐effectiveness model

Abstract

Background Acquired haemophilia A (AHA) is an autoimmune bleeding disorder with significant morbidity and mortality. Bleeding AHA patients with high titre inhibitors can be treated with either activated prothrombin complex concentrate (aPCC) or recombinant activated factor VII (rFVIIa). Given that both replacement therapies have inherent benefits and limitations, a cost‐effectiveness analysis (CEA) was performed in this population to compare rFVIIa with aPCC. Methods In high‐titered AHA patients with bleeding treated with either aPCC or rFVIIa, during a 5‐day study period, a Markov model was developed such that these patients were transitioned into four different health states: (1) continuous bleeding, (2) thrombosis, (3) stop bleeding and (4) death, with states (2), (3) and (4) modelled as absorbing states. Model parameters, including probabilities, health utility index and costs, were gathered from the medical literature, except for the costs of aPCC and rFVIIa, which were obtained from our institutional data. Results During the 5‐day period, the total treatment cost of rFVIIa was substantially more than the cost of aPCC ($13 635 vs. $1741). The average quality‐adjusted life days (QALDs) gained for rFVIIa were slightly lower compared to aPCC (4·08 vs. 4·09). Overall, aPCC prevailed over rFVIIa. Sensitivity analysis confirmed the robustness of the model across tested ranges of all input variables. Conclusion In high‐titered AHA patients with bleeding, aPCC is a cost‐effective treatment option when compared to rFVIIa. Thus, aPCC may be considered in these patients, if available, and provided there is no clinical contraindication.

An economic analysis of different treatments for bleeding in patients with acquired haemophilia

“…The adult patient population was similar to the one we previously described with a modification to the Markov decision analytic model (Fig. ) that was developed using Microsoft Excel (Microsoft Corporation, Redmond, WA, USA) so that these hypothetical hospitalized, high‐titred (>5 Bethesda units [BU]) AHA patients with bleeding could also be treated with rpFVIII (represented by Obizur, Baxter, Westlake Village, CA, USA) in addition to aPCC (represented by FEIBA, Shire, Lexington, MA, USA) and rFVIIa (represented by NovoSeven, Novo Nordisk, Plainsboro, NJ, USA) .…”

“…) that was developed using Microsoft Excel (Microsoft Corporation, Redmond, WA, USA) so that these hypothetical hospitalized, high‐titred (>5 Bethesda units [BU]) AHA patients with bleeding could also be treated with rpFVIII (represented by Obizur, Baxter, Westlake Village, CA, USA) in addition to aPCC (represented by FEIBA, Shire, Lexington, MA, USA) and rFVIIa (represented by NovoSeven, Novo Nordisk, Plainsboro, NJ, USA) . In brief, regardless of the treatment, similar to our previous study, the model allowed the patients to be transitioned into four different health states: (1) continuous bleeding, (2) thrombosis, (3) stop bleeding and (4) death . All patients entered the model at stage (1) because they were bleeding initially, and whether they remained in state (1) or entered the other states depended on the efficacy of the treatment and the probability of an adverse event.…”

“…As mentioned in our previously published study, the cost‐effectiveness analysis (CEA) was conducted from the US payer perspective , without inflation adjustment during the 6‐day study period . Because of the disease's low incidence, the heterogeneity of published studies, and the uncertainty around the costs and effectiveness of the treatment options, given a lack of comparative trials, our primary outcomes of interest were an estimation of the joint density of cost and effectiveness differences and the quantification of uncertainty surrounding the incremental cost‐effectiveness ratios (ICER, .…”

“…Traditionally, in bleeding patients whose factor VIII inhibitors are high‐titred, bypassing medications, including recombinant activated factor VII (rFVIIa) and activated prothrombin complex concentrate (aPCC), both FDA‐approved for treatment of this condition, should be initiated promptly . We previously showed that aPCC is a more cost‐effective option than rFVIIa in this clinical scenario . Recently, recombinant porcine‐sequence factor VIII (rpFVIII) was also approved by the FDA for this indication after a phase 2/3 multicentre trial showing its efficacy and safety .…”

“…Furthermore, rpFVIII is relatively more expensive compared to aPCC or rFVIIa . Focusing on the population of high‐titred AHA patients, given its high morbidity and mortality and the availability of three FDA‐approved therapies currently for the treatment of bleeding in these patients, from a global healthcare policy perspective, we adapted our previously published economic model to rigorously examine the cost‐effectiveness of the new treatment, namely, rpFVIII, against traditional options of aPCC or rFVIIa, using actual institutional costs, clinical outcome data and complication data obtained from the literature.…”