Long‐term FEIBA prophylaxis does not prevent progression of existing joint disease

Abstract

Activated prothrombin complex concentrates have been used to treat bleeding episodes for patients who have developed an inhibitor to factor VIII (FVIII). FEIBA-Vh (FVIII bypassing activity, FEIBA) has been used since 1970 for this purpose and with FVIII for immune tolerance programmes. Studies have not been presented to show the safety and efficacy of FEIBA when given over a long period of time to prevent haemophilic arthropathy with bleeding into the joints of these patients. This study was undertaken to ascertain the outcome of haemophilic arthropathy with FEIBA prophylaxis. Data were collected on seven patients with known long-standing high-titre FVIII inhibitors given FEIBA prophylaxis for 3-6(1/2) years. Patients were given 50-100 units of FEIBA three to four times weekly. A functional joint evaluation revealed some degree of arthropathy already present in all patients at time of prophylaxis initiation. Safety was measured by medical status, evidence of thrombosis, life-threatening bleeding and inhibitor titre. Efficacy was measured for joint outcome by a functional physical therapeutic scale. At the conclusion of the study, efficacy was mixed as all of the joints for which the patients were placed on prophylaxis had progressed and developed synovitis. Two patients had a functional improvement in their arthropathy, and all were functional enough to attend regular school. The product was deemed safe for long-term use, as there were no complications of therapy with no thrombosis, no life-threatening bleeding episodes and no anamnesis caused by FEIBA alone. Inhibitor titres fell in all patients over the course of the study. Total product usage ranged from approximately 9373-15,571 U kg(-1) year(-1). FEIBA is safe for long-term prophylaxis when given in the recommended dosage for an extended period of time. Efficacy to prevent arthropathy could not be seen as all patients had some degree of arthropathy at time of prophylaxis initiation. An additional study needs to be performed using FEIBA before arthropathy has developed.

Successful self‐infusion of activated prothrombin complex concentrate for prophylaxis in a child with a factor VIII inhibitor

“…Treatment duration across these studies varied from a few months to several years. Consistent with the current case report, two of the previous studies also found decreased inhibitor titers during FEIBA prophylaxis [8,10]. Notably, studies by Escuriola-Ettingshausen et al [9], Valentino and Salit [12], and Leissinger [7] also showed maintenance or improvement of existing arthropathy.…”

“…While this case represents a novel experience in the treatment of inhibitor-positive patients in Japan, the findings are consistent with data from other patients treated prophylactically with FEIBA [6,[8][9][10][11][12], which reported low or decreased (relative to pretreatment) bleeding episode frequencies for patients treated with a variety of FEIBA regimens, including 50-100 U three or four times per week, or 50 or 100 U/kg/day. Treatment duration across these studies varied from a few months to several years.…”

“…Home-based prophylactic regimens are well established for the prevention of serious bleedings and joint diseases in patients without inhibitors [13], whereas prophylactic replacement in inhibitor-positive patients has been reported for a limited number of patients [6,[8][9][10][11][12]. The current report describes successful self-infusion of an APCC, FEIBA, at a dose of 50 U/kg, three times per week, by a 14-year-old Japanese boy with severe hemophilia A and a high-titer inhibitor, who had experienced recurrent bleeding during long-term prophylaxis with a PCC.…”

“…Regular prophylactic replacement with PCC or APCC, however, has not been used routinely in inhibitor-positive patients in the United States, as controlled trials of prophylaxis have not been conducted and there is no consensus on standard dosing [7]. There are several reports on the efficacy for prevention of bleeding by PCC or APCC in patients with inhibitors [6,[8][9][10][11][12]. To determine the safety and efficacy of PCC and APCC for prophylaxis, long-term observations are needed for sufficient number of patients.…”

Anti-Inhibitor Coagulant Complex Prophylaxis in Hemophilia with Inhibitors

“…Although anecdotal reports [13][14][15][16] have suggested that regular administration of AICC may prevent bleeding in patients with hemophilia A and factor VIII inhibitors, the efficacy of this therapeutic regimen has been unproved. The Prophylaxis with Factor Eight Inhibitor Bypassing Activity (Pro-FEIBA) study was designed to compare the efficacy and safety of AICC prophylaxis with ondemand therapy in this patient population.…”