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

Abstract

Background Acquired haemophilia A (AHA), with potentially high risk of morbidity and mortality, occurs as a result of inhibitors against factor VIII. Bleeding due to AHA can be treated with activated prothrombin complex concentrate (aPCC), recombinant activated factor VII (rFVIIa) or recently, recombinant porcine-sequence factor VIII (rpFVIII). We extended our previous cost-effectiveness analysis (CEA) comparing rpFVIII against the available traditional options.Methods For high-titred, haemorrhaging AHA patients treated with either aPCC, rFVIIa or rpFVIII, over the course of 6-days, a Markov simulation was conducted to evaluate the outcomes when these patients transitioned into any of the four following health states: (1) continuous bleeding, (2) thrombosis, (3) stop bleeding and (4) death, with states (2), (3) and (4) modelled as absorbing states. All model parameters were obtained from the medical literature, except the costs of aPCC, rFVIIa and the factor VIII assay, which came from our institutional data.Results Excluding the cost of the initial treatment on day 0, the total subsequent treatment cost of rFVIIa was substantially more than the costs of aPCC and rpFVIII ($13 925 vs. $1778 vs. $6957, respectively). The average quality-adjusted life days (QALDs) gained from rpFVIII was lowest (4Á89 vs. 4Á9 for rFVIIa and 4Á91 for aPCC). Overall, aPCC dominated the other two treatments. The model was determined to be robust across the tested ranges for all input variables. ConclusionBased on this economic model, for AHA patients with high titres who were bleeding, aPCC was the most cost-effective treatment option and may be considered for use if there is no clinical contraindication.

Recombinant porcine FVIII for bleed treatment in acquired hemophilia A: findings from a single-center, 18-patient cohort

“…An economic analysis of AHA treatment reported rpFVIII costs as being comparable to using rFVIIa if factor utilization can be reduced by 50%, along with pharmacy cost reduction of 30%. 27,28 Using the proposed algorithm, we have, on average, used ;70% less rpFVIII in the first 24 hours, and 42% less cumulative product for initial bleed control as compared with recommended dosing in the phase 2/3 trial. This difference in cumulative product utilization for bleed treatment may greatly mitigate cost concerns for a treating institution.…”

Post COVID-19 acquired haemophilia A treated with recombinant porcine factor VIII

“…The cost of the rpFVIII therapy varies because the dosage of this bypassing agent (as the only one) is adjusted to the peak and trough levels of factor VIII. In terms of cost-effectiveness the economic analysis by Kim et.al., demonstrated that rpFVIII therapy comes second after aPCC [12]. Fortunately, the rpFVIII therapy is refunded in Poland and it is now accessible just as any other bypassing therapy.…”

Emicizumab for the treatment of acquired hemophilia A: Retrospective review of a single‐institution experience

“…For severe bleeding, haemostatic therapies include recombinant porcine FVIII or, particularly for patients with high‐titre inhibitors > 5 Bethesda units, bypassing products such as recombinant activated factor VII (rFVIIa) or activated prothrombin complex concentrates (aPCC) 7 . However, these products have high cost and short half‐lives 7,10 . To eliminate the inhibitor, immunosuppressive therapy (IST) with corticosteroids, cyclophosphamide, rituximab or a combination of these agents are used, but IST‐related adverse events, particularly sepsis, are associated with a higher mortality than even the risk of fatal bleeding 1,4,9,11 .…”

“…7 However, these products have high cost and short half-lives. 7,10 To eliminate the inhibitor, immunosuppressive therapy (IST) with corticosteroids, cyclophosphamide, rituximab or a combination of these agents are used, but IST-related adverse events, particularly sepsis, are associated with a higher mortality than even the risk of fatal bleeding. 1,4,9,11 Several months of IST may be required before remission is achieved, during which patients may rebleed and require additional haemostatic therapies.…”