Abstract
Introduction
The primary treatment for mild-to-moderate bleeding disorders in hemophilia is either recombinant activated factor VII (rFVIIa) or activated prothrombin complex concentrate (aPCC). The efficacy of both products has been evaluated in individual studies; however, there has not been an overall review to compare the efficacy from these individual studies of rFVIIa and aPCC. Our aim is to establish robust estimates of the efficacy, speed of bleed resolution, and adverse event profile of both rFVIIa and aPCC.
Methods
A systematic review was conducted of the relevant literature.
Results
We identified 11 open-label cohort studies, six randomized clinical trials, including two head-to-head clinical trials, and a meta-analysis. The definition of efficacy varies between these studies, but is usually a composite measure of definite pain relief, reduction in the size of the hemorrhage, and cessation of bleeding. The individual making the interpretation of efficacy and the time from treatment initiation to recording the efficacy endpoint also varies across the studies. Overall, estimates of efficacy from randomized clinical trials using dosing regimens in line with the guidelines are higher for rFVIIa (81%–91%) than for aPCC (64%–80%). Conclusions from a meta-analysis suggest that treatment with rFVIIa may be associated with a faster time to joint bleed resolution than aPCC due to higher efficacy levels at different time points. The results from a comparative trial support the improved efficacy rates associated with rFVIIa compared with aPCC.
Conclusion
The wide variations in definitions of efficacy and study methods make comparison of results across studies difficult. Further head-to-head trials should incorporate a standardized measurement for defining efficacy.
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References
Astermark J, Donfield SM, DiMichele DM, et al. A randomized comparison of bypassing agents in hemophilia complicated by an inhibitor: the FEIBA NovoSeven Comparative (FENOC) study. Blood. 2007;109:546–551.
Young G, Shafer FE, Rojas P, Seremetis S. Single 270μg kg -1 dose rFVIIa vs. standard 90 μg kg -1 dose rFVIIa and APCC for home treatment of joint bleeds in haemophilia patients with inhibitors: a randomized comparison. Haemophilia. 2008;14:287–294.
Lusher JM, Roberts HR, Davignon G, et al. A randomized double-blind comparison of low dosage levels of recombinant factor VIIa in the treatment of joint, muscle and mucocutaneous haemorrhages in persons with haemophilia A and B, with and without inhibitors. Haemophilia. 1998;4:790–798.
Santagostino E, Mancuso ME, Rocino A, Mancuso G, Scaraggi F, Mannucci PM. A prospective randomized trial of high and standard dosages of recombinant factor VIIa for treatment of hemarthroses in hemophiliacs with inhibitors. J Thromb Haemost. 2006;4:367–371.
Kavakli K, Makris M, Zulfikar B, et al. Home treatment of haemarthroses using a single dose regimen of recombinant activated factor VII in patients with haemophilia and inhibitors. Thromb Haemost. 2006;95:600–605.
Sjamsoedin LJM, Heijnen L, Mauser-Bunschoten EP, et al. The effect of activated prothrombincomplex concentrate (FEIBA) on joint and muscle bleeding in patients with haemophilia A and antibodies to factor VIII. N Engl J Med. 1981;305:717–721.
Hilgartner MW, Knatterud GL. FEIBA Study Group. The use of factor eight inhibitor by-passing activity (FEIBA Immuno) product for treatment of bleeding episodes in hemophiliacs with inhibitors. Blood. 1983;61:36–40.
Hilgartner M, Aledort L, Andes A, Gill J. FEIBA Study Group. Efficacy and safety of vapor-heated anti-inhibitor coagulant complex in hemophilia patients. Transfusion. 1990;30:626–630.
DiMichele D, Negrier C. A retrospective postlicensure survey of FEIBA efficacy and safety. Haemophilia. 2006;12:352–362.
Negrier C, Goudemand J, Sultan Y, et al. Multicenter retrospective study on the utlization of FEIBA in France in patients with factor VIII and factor IX inhibitors. Thromb Haemost. 1997;77:1113–1119.
Negrier C. French FEIBA Study Group. FEIBA VH in home treatment - a 3-year experience. Haemophilia. 1998;4:238. Abstract 330.
Key NS, Aledort LM, Beardsley D, et al. Home treatment of mild to moderate bleeding episodes using recombinant factor VIIa (Novoseven) in haemophiliacs with inhibitors. Thromb Haemost. 1998;80:912–918.
Shirahata A, Kamiya T, Takamatsu J, et al. Clinical trial to investigate the pharmacokinetics, pharmacodynamics, safety, and efficacy of recombinant factor VIIa in Japanese patients with hemophilia with inhibitors. Int J Hematol. 2001;73:517–525.
Parameswaran R, Shapiro AD, Gill JC, Kessler CM. HTRS Registry Investigators. Dose effect and efficacy of rFVIIa in the treatment of haemophilia patients with inhibitors: analysis from the Hemophilia and Thrombosis Research Society Registry. Haemophilia. 2005;11:100–106.
Bech RM. Recombinant factor VIIa in joint and muscle bleeding episodes. Haemostasis. 1996;26(suppl. 1):135–138.
Laurian Y, Goudemand J, Negrier C, et al. Use of recombinant activated factor VII as first-line therapy for bleeding episodes in haemophiliacs with factor VIII or IX inhibitors (NOSEPAC study). Blood Coagul Fibrinolysis. 1998;9(suppl. 1):S155–S156.
Santagostino E, Gringeri A, Mannucci PM. Home treatment with recombinant activated factor VII in patients with factor VIII inhibitors: the advantages of early intervention. Br J Haematol. 1999;104:22–26.
Hay CR, Brown S, Collins PW, Keeling DM, Liesner R. The diagnoses and management of factor VIII and IX inhibitors: a guideline from the United Kingdom Haemophilia Centre Doctors Organisation. Br J Haematol. 2006;133:591–605.
Treur MJ, McCracken F, Heeg B, et al. Efficacy of recombinant activated factor VII (rFVIIa) vs. activated prothrombin complex concentrate (APCC) in patients with hemophilia with inhibitors: a Bayesian meta-analysis. Blood. 2007;110:3964. Abstract.
Lusher JM. Acute hemarthroses: the benefits of early versus late treatment with recombinant activated factor VII. Blood Coagul Fibrinolysis. 2000;11(suppl. 1):S45–S49.
Prescribing information for NovoSeven ®. Revised May 2008. Available at: www.fda.gov/CBER/label/novosevenrtLB.pdf. Accessed November 2008.
Mauser-Bunschoten EP, Nieuwenhuis HK, Roosendaal G, van den Berg HM. Low-dose immune tolerance induction in hemophilia A patients with inhibitors. Blood. 1995;86:983–988.
Brackmann HH, Effenberger E, Hess L, Schwaab R, Oldenburg J. NovoSeven in immune tolerance therapy. Blood Coagul Fibrinolysis. 2000;11(suppl. 1):S39–S44.
Chow S-C, ed. Encyclopedia of Biopharmaceutical Statistics. 2nd edition. Informa Healthcare; 2003.
Miners AH, Sabin CA, Tolley KH, Jenkinson C, Kind P, Lee CA. Assessing health-related quality-of-life in individuals with haemophilia. Haemophilia. 1999;5:378–385.
Luu H, Ewenstein B. FEIBA safety profile in multiple modes of clinical and home-therapy application. Haemophilia. 2004;10(suppl. 2):10–16.
Santagostino E, Mannucci PM, Gringeri A, et al. Transmission of parvovirus B19 by coagulation factor concentrates exposed to 100 degrees C heat after lyophilization. Transfusion. 1997;37:517–522.
Soucie JM, Siwak EB, Hooper WC, Evatt BL, Hollinger FB. Universal Data Collection Project Working Group. Human parvovirus B19 in young male patients with hemophilia A: associations with treatment product exposure and joint range-of-motion limitation. Transfusion. 2004;44:1179–1185.
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Knight, C., Danø, A.M. & Kennedy-Martin, T. Systematic review of efficacy of rFVIIa and aPCC treatment for hemophilia patients with inhibitors. Adv Therapy 26, 68–88 (2009). https://doi.org/10.1007/s12325-008-0135-6
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DOI: https://doi.org/10.1007/s12325-008-0135-6