Recombinant Factor IX Recovery and Inhibitor Safety: A Canadian Post-licensure Surveillance Study

Man-Chiu Poon; David Lillicrap; Caroline Hensman; Robert Card; Mary-Frances Scully; Members of Asso cia tion of Hemophilia Clinic Directors of Canada* and Canadian Association of Nurses in Hemophilia Care*

doi:10.1055/s-0037-1613022

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2002; 87(03): 431-435
DOI: 10.1055/s-0037-1613022

Review Article

Schattauer GmbH

Recombinant Factor IX Recovery and Inhibitor Safety: A Canadian Post-licensure Surveillance Study

Man-Chiu Poon

¹University of Calgary, Calgary, Alberta

,

David Lillicrap

²Queen’s University, Kingston, Ontario, University of Saskatchewan, Saskatoon, Saskatchewan, Memorial University, St. John’s, Newfoundland, AHCDC, Toronto, Ontario, Canada

,

Caroline Hensman

,

Robert Card

,

Mary-Frances Scully

,

Members of Asso cia tion of Hemophilia Clinic Directors of Canada* and Canadian Association of Nurses in Hemophilia Care*

› Author Affiliations

Abstract

Summary

As part of the Canadian post-licensure surveillance on the safety of recombinant factor IX (rFIX, BeneFIX^®), factor IX recovery and inhibitor development were studied. The recovery following rFIX infusion in 126 patients (mean = 0.77, median 0.72, range 0.36-1.85, 95% CI of mean 0.74-0.81, expressed as FIX activity increase in U/dL per IU FIX concentrate/kg body weight infused) was significantly lower than that following the last plasma-derived factor IX (pdFIX) infusion in 74 patients (mean 1.05, median 1.00, range 0.37-2.29, 95% CI of mean 0.99-0.97). The recovery for rFIX for patients aged ≤15 years (n = 41, mean recovery 0.64) and that for patients aged >15 years (n = 85, mean 0.84) was each significantly lower than that for pdFIX (aged ≤15 years: n = 21, mean recovery 0.91; aged >15 years: n = 53, mean recovery 1.10). For both rFIX and pdFIX concentrates, the recovery was lower in patients ≤15 years of age compared to those >15 years of age. Similar data and conclusions were obtained on 66 patients with paired recovery data from rFIX and pdFIX. Overall, our data are similar to those obtained in formal clinical trials. Two of 244 patients treated with rFIX for up to 5 years have developed de novo inhibitors associated with anaphylaxis, an incidence that is similar to that reported for pdFIX. No other serious adverse events, including thrombotic episodes, were reported. To the best of our knowledge, this is the first formal report of recovery and inhibitor formation on rFIX in a peer-reviewed manuscript form.

Keywords

Recombinant factor IX - plasma-derived factor IX - recovery - inhibitor - surveillance - safety

Full Text

References

References
1 Arun B, Kessler CM. Clinical manifestations and therapy of the hemophilias. In: Hemostasis and Thrombosis. Basic Principles & Clinical Practice. Colman RW, Hirsh J, Marder VJ, Clowes AW, George JN. eds. 4th edition. Philadelphia: Lippincott Williams & Wilkins; 2001: 815-37.
2 White GC, Beebe A, Nielsen B. Recombinant factor IX. Thromb Haemost 1997; 78: 261-5.
3 White G, Shapiro A, Ragni M, Garzone P, Goodfellow J, Tubridy K. et al. Clinical evaluation of recombinant factor IX. Semin Hematol 1998; 35: 33-8.
4 Kessler C, Poon M, Negrier C, Fernands A, Gencarella N. the Recombinant Factor IX Study Group. Recombinant factor IX is an effective and safe replacement therapy for previously treated patients with hemophilia B. Thromb Haemost. 1999 331. (Suppl). (Ref Type: Abstract).
5 Shapiro A, Abshire T, Kisker CT, Peerlinck K, Fernands A. the Recombinant Factor IX Study Group. Recombinant factor IX (rFIX) treatment of previously untreated patients (PUPs) with severe or moderately severe haemophilia B. Haemophilia 2000; 06 (04) 366 (Ref Type: Abstract).
6 Ewenstein BM, Joist JH, Shapiro A, Hofstra T, Leissinger C, Seremetis S, Broder M, Mueller-Velten G, Schwartz BA. for the Mononine Comparison Study Investigators. Factor IX pharmacokinetics of a plasma-derived and a recombinant factor IX concentrate (Mononine vs. BeneFix) in previously treated subjects with moderate or severe haemophilia B. Haemophilia 2000; 06 (04) 365 (Ref Type: Abstract).
7 Bjorkman S, Shapiro AD, Berntorp E. Pharmacokinetics of recombinant factor IX in relation to age of the patient: implications for dosing in prophylaxis. Haemophilia 2001; 07: 133-9.
8 Aronstam A, McLellan DS, Wassef M, Mbatha PS. Effect of height and weight on the in vivo recovery of transfused factor VIII C. J Clin Pathol 1982; 35: 289-91.
9 Manno CS, Butler RB, Cohen AR. Low recovery in vivo of highly purified factor VIII in patients with hemophilia. J Pediatr 1992; 121: 814-8.
10 White GC, Shapiro AD, Kurczynski EM, Kim HC, Bergman GE. Variability of in vivo recovery of factor IX after infusion of monoclonal antibody purified factor IX concentrates in patients with hemophilia B. The Mononine Study Group. Thromb Haemost 1995; 73: 779-84.
11 Erhardtsen E. Pharmacokinetics of recombinant activated factor VII (rFVIIa). Semin Thromb Hemost 2000; 26: 385-91.
12 Morfini M, Lee M, Messori A. The design and analysis of half-life and recovery studies for factor VIII and factor IX. Factor VIII/Factor IX Scientific and Standardization Committee of the International Society for Thrombosis and Haemostasis. Thromb Haemost 1991; 66: 384-6.
13 Briet E, Reisner HM, Roberts HR. Inhibitors in Christmas disease. Prog Clin Biol Res 1984; 150: 123-39.
14 Warrier I, Ewenstein BM, Koerper MA, Shapiro A, Key N, DiMichele D. et al. Factor IX inhibitors and anaphylaxis in hemophilia B. J Pediatr Hematol Oncol 1997; 19: 23-7.