An overview of the history, clinical practice concerns, comparative studies and strategies to optimize therapy of bypassing agents

Abstract

Despite significant advances in the treatment of haemophilia, including availability of recombinant coagulation factor replacement products and the use of prophylactic infusion regimens, the segment of haemophilic patients who develop inhibitory antibodies remain at higher risk for morbidity and mortality associated with recurrent or uncontrolled bleeding events. Bypassing agents represent the mainstay of treatment and prevention of bleeding. The most commonly used of the currently available therapeutic agents are a plasma-based therapy, factor eight inhibitor bypassing activity, vapour heated, and a recombinant therapy, NovoSeven (recombinant activated factor VIIa). A substantial body of literature exists to document efficacy and adverse event profiles for these two products. There is, however, a paucity of data arising from adequately powered prospective trials to determine optimal treatment and dosing in various clinical situations. Certain clinical circumstances, patient profiles, individual responses, or provider predilection may lead to preferential use of one of these products over the other; however, the continued presence of both agents in the therapeutic armamentarium remains critically important to this fragile population. The historical use, clinical practice concerns, published comparative studies and methods for optimization of these two bypassing agents are reviewed.

Optimizing management of immune tolerance induction in patients with severe haemophilia A and inhibitors: towards evidence‐based approaches

“…Although on-demand treatment with by-passing agents has been progressively optimized (Mehta et al, 2006) and by-passing agent prophylaxis has been increasingly employed (Konkle et al, 2007;Valentino, 2009;Carcao & Lambert, 2010), on the whole patients with inhibitors experience a higher morbidity (UK Haemophilia Centre Doctors ' Organization, 2004) and a worse orthopaedic status and quality of life (Gringeri et al, 2003;Scalone et al, 2006;Morfini et al, 2007a) than non-inhibitor patients. Moreover, economic implications of such a complication are strikingly relevant (Gringeri et al, 2003).…”

FEIBA®in treatment of acute bleeding episodes in patients with haemophilia A and factor VIII inhibitors: a retrospective survey in regional haemophilia centre

“…The first use in haemophilia patients with inhibitor was reported in 1988 and commercially it has been used since 1996 in Europe and since 1999 in the USA [5].…”

“…Autoplex T Ò is no longer commercially available [5] and was replaced by Factor Eight Inhibitor By-passing Activity (FEIBA Ò ; Baxter AG, Vienna, Austria). This product has been used to achieve haemostasis in haemophiliacs with inhibitor since 1974 [6] and has been commercially available since 1977.…”

Factor VIII gene (F8) mutations as predictors of outcome in immune tolerance induction of hemophilia A patients with high‐responding inhibitors

“…FVIII inhibitors occur in about 30% of severely affected patients (FVIII:C < 1%), usually during the first 20 days of exposure to FVIII [3], as a result of a complex process involving multiple genetic and environmental factors [4]. Although strategies of treatment of bleeds with bypassing agents have progressively improved, and prophylactic regimens are being also experienced in patients with inhibitors [5,6], the presence of high-responding inhibitors precludes FVIII concentrate treatment and prophylaxis, most effective standard of care. These patients, in comparison with non-inhibitor patients, experience higher levels of morbidity and mortality [7] and a worse quality of life -predominantly due to their poor orthopedic status [2,8,9].…”