Review of recombinant anti-haemophilic porcine sequence factor VIII in adults with acquired haemophilia A

Abstract

Acquired haemophilia A (AHA) is a rare, serious bleeding disorder most often encountered in elderly patients. The mainstay of haemostatic management is with bypassing agents (BPAs) including recombinant activated factor VII (rFVIIa) and activated prothrombin complex concentrates (aPCCs). Their major limitation is incomplete efficacy, potential risk for thrombosis and the lack of routine laboratory assays for monitoring treatment response. Plasma-derived porcine FVIII (pd-pFVIII, Hyate C), first used in the 1950s for the management of congenital haemophilia, has sufficient sequence homology to be haemostatic in humans, but the lack of complete homology facilitates efficacy even in the presence of human allo- and autoantibodies against human FVIII (hFVIII). In a small phase II/III study, recombinant porcine FVIII (rpFVIII, Obizur, OBI-1, susoctocog alfa) was shown to be safe and effective for the management of bleeding episodes in patients with AHA with anti-porcine FVIII (anti-pFVIII) antibody levels of 20 BU/ml or less. Treatment outcome was judged on clinical response and FVIII levels after an initial fixed dose of 200 IU/kg. The rise in FVIII levels showed considerable inter-individual variability and was significantly influenced by the presence of anti-pFVIII antibodies. Based on the baseline levels of anti-pFVIII antibodies and response to treatment, three potential patient groups were identifiable. In the first group, the absence of cross-reacting antibodies was associated with supra-therapeutic FVIII levels, fewer infusions and lower rpFVIII utilization per treatment episode. The second group had patients with low levels of cross-reacting anti-pFVIII antibodies (0.8-5 BU/ml) with near-normal response to rpFVIII. The last group had higher titres of anti-pFVIII antibody (10-30 BU/ml) associated with lower FVIII levels, more infusions and higher consumption of rpFVIII. We propose a new treatment algorithm for the haemostatic management of AHA that includes the potential first-line clinical use of rpFVIII that takes into account availability of anti-pFVIII antibody results, titre of anti-pFVIII antibodies and severity of bleeding episode.

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) . 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 .…”

“…In addition, after the approval, there have been several studies describing its successful real‐world usage . Unlike aPCC or rFVIIa (which are given as fixed doses without routine monitoring and hence, theoretically, can be associated with thrombotic complications), the dosage of rpFVIII can be adjusted based on the measured peak and trough level of factor VIII . Therefore, this can be an advantage in using rpFVIII.…”

Acquired Hemophilia A: A Case Report

“…8 Recombinant porcine factor VIII (rpFVIII) has been approved by the Food and Drug Administration and has shown positive results in real-world practice. 9 FVIIa is most frequently used as first-line therapy. Studies showed that rFVIIa and APCC have an overall efficacy of 90%, [10][11][12] while rpFVIII has been shown in small studies to have an efficacy of around 86%.…”

“…Studies showed that rFVIIa and APCC have an overall efficacy of 90%, [10][11][12] while rpFVIII has been shown in small studies to have an efficacy of around 86%. 9 Desmopressin can be useful in treating minor bleeding as it increases the amount of clotting FVIII and tissue plasminogen activator. However, the use of desmopressin should not delay the use of a bypassing agent.…”

Management of Acquired Hemophilia A in Elderly Patients

“…Treatment goals for AHA comprise hemostasis and inhibitor eradication [ 1 , 3 ]. To control bleeding, previous authors have advocated the use of bypassing agents, including recombinant activated factor VII (rFVIIa; NovoSeven®) and/or activated prothrombin complex concentrate (APCC; Feiba®), as well as recombinant porcine FVIII [ 5 ]. Challenges in the management of AHA in elderly patients include (1) delayed diagnosis probably due to the relatively low prevalence of AHA, differentiation from other bleeding disorders, and the fact that patients typically present to nonhematologists; (2) the presence of comorbid disease often complicates the administration of prednisolone as well as the selection of hemostatic and immunosuppressive agents; (3) frequent need of anticoagulants in association with poor venous access; (4) high costs of therapy; and (5) thromboembolic risk when FVIII returns to normal.…”