INTRODUCTION: Antihaemophilic factor (recombinant) (rAHF; ADVATE® ) is approved for prophylaxis and treatment of bleeding in children and adults with haemophilia A. Reconstitution in 2 mL sterile water for injection instead of 5 mL allows for a 60% reduction in infusion volume and administration time, but could increase the likelihood of hypersensitivity and infusion-related reactions, especially in children. AIM: To assess local tolerability, safety and effectiveness of rAHF 2 mL during routine clinical practice factor VIII (FVIII) replacement (on-demand and prophylaxis) in children with severe (FVIII < 1%) or moderately severe (FVIII 1%-2%) haemophilia A. METHODS: This was a prospective, non-interventional, postauthorization safety surveillance study (NCT02093741). Eligible patients were previously treated with rAHF and had a negative inhibitor test result during ≤10 exposure days prior to study entry. RESULTS: Of 65 patients enrolled (0-11 years of age), 54 and 11 had severe and moderately severe haemophilia A, respectively; 56 patients received prophylaxis, and 11 had ≤50 exposure days, of which 4 had ≤4 exposure days. No patients reported local hypersensitivity reactions, treatment-related adverse events or developed inhibitors. Investigators rated overall effectiveness of rAHF 2 mL prophylaxis as excellent or good. Ninety-four bleeding events in 34 patients were treated. Haemostatic effectiveness was rated as excellent or good for 75.8% of bleeds; 86.2% of bleeds required 1 or 2 infusions. CONCLUSION: In children with severe/moderately severe haemophilia A, no hypersensitivity reactions were reported with rAHF 2 mL treatment, and the safety and effectiveness are consistent with data previously reported for rAHF 5 mL.

Baxalta Innovations GmbH a member of the Takeda group of companies Vienna Austria

Baxalta US Inc a member of the Takeda group of companies Lexington MA USA

Birmingham Children's Hospital Birmingham UK

Children's University Hospital Brno Brno Czech Republic

CRTH Institut Coeur Poumon CHU Lille France

IRSET Rennes University Hospital and Inserm U1085 Rennes France

Luzerner Kantonsspital Lucerne Switzerland

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Shapiro AD. Anti‐hemophilic factor (recombinant), plasma/albumin‐free method (octocog‐alpha; ADVATE) in the management of hemophilia A. Vasc Health Risk Manag. 2007;3(5):555‐565. PubMed PMC

Berntorp E, Spotts G, Patrone L, Ewenstein BM. Advancing personalized care in hemophilia A: ten years' experience with an advanced category antihemophilic factor prepared using a plasma/albumin‐free method. Biologics. 2014;8:115‐127. PubMed PMC

Baxalta US Inc . ADVATE [antihemophilic factor (recombinant)] Prescribing Information. Westlake Village, CA: Baxter Healthcare Corporation; 2016.

European Medicines Agency . ADVATE. Summary of product characteristics. https://www.ema.europa.eu/en/documents/product‐information/advate‐epar‐product‐information_en.pdf. Accessed February 28, 2019.

Thornburg CD, Pipe SW. Adherence to prophylactic infusions of factor VIII or factor IX for haemophilia. Haemophilia. 2006;12(2):198‐199. PubMed

De Moerloose P, Urbancik W, Van Den Berg HM, Richards M. A survey of adherence to haemophilia therapy in six European countries: results and recommendations. Haemophilia. 2008;14(5):931‐938. PubMed

Thornburg CD, Duncan NA. Treatment adherence in hemophilia. Patient Prefer Adher. 2017;11:1677‐1686. PubMed PMC

Verbruggen B, Novakova I, Wessels H, Boezeman J, van den Berg M, Mauser‐Bunschoten E. The Nijmegen modification of the Bethesda assay for factor VIII:C inhibitors: improved specificity and reliability. Thromb Haemost. 1995;73(2):247‐251. PubMed

Kasper CK, Aledort L, Aronson D, et al. Proceedings: a more uniform measurement of factor VIII inhibitors. Thromb Diath Haemorrh. 1975;34(2):612. PubMed

Iorio A, Marcucci M, Cheng J, et al. Patient data meta‐analysis of Post‐Authorization Safety Surveillance (PASS) studies of haemophilia A patients treated with rAHF‐PFM. Haemophilia. 2014;20(6):777‐783. PubMed

Oldenburg J, Goudemand J, Valentino L, et al. Postauthorization safety surveillance of ADVATE [antihaemophilic factor (recombinant), plasma/albumin‐free method] demonstrates efficacy, safety and low‐risk for immunogenicity in routine clinical practice. Haemophilia. 2010;16(6):866‐877. PubMed

Shapiro A, Gruppo R, Pabinger I, et al. Integrated analysis of safety and efficacy of a plasma‐ and albumin‐free recombinant factor VIII (rAHF‐PFM) from six clinical studies in patients with hemophilia A. Expert Opin Biol Ther. 2009;9(3):273‐283. PubMed

Blanchette VS, Shapiro AD, Liesner RJ, et al. Plasma and albumin‐free recombinant factor VIII: pharmacokinetics, efficacy and safety in previously treated pediatric patients. J Thromb Haemost. 2008;6(8):1319‐1326. PubMed

Tarantino MD, Collins PW, Hay CR, et al. Clinical evaluation of an advanced category antihaemophilic factor prepared using a plasma/albumin‐free method: pharmacokinetics, efficacy, and safety in previously treated patients with haemophilia A. Haemophilia. 2004;10(5):428‐437. PubMed

European Medicines Agency . Report of Expert Meeting on Factor VIII Products and Inhibitor Development: 28 February 2006–2 March 2006. London, UK: European Medicines Agency; 2007. EMEA/CHMP/BPWP/123835/2006.

ADVATE (antihemophilic factor [recombinant]) Prescribing Information. Westlake Village, California: Baxalta US Inc.; 2016.

NUWIQ (antihemophilic factor [recombinant]) Prescribing Information. Hoboken, New Jersey: Octapharma USA, Inc.; 2015.

KOVALTRY (antihemophilic factor [recombinant]) Prescribing Information. Whippany, New Jersey: Bayer HealthCare LLC; 2016.

AFSTYLA (antihemophilic factor [recombinant], single chain) Prescribing Information. Kankakee, Illinois: CSL Behring LLC; 2017.

Butler RB, Jaworski K, Zappa S, Abbruzzesem A, Davis J, Gorina E. Clinical convenience of low volume factor VIII infusions in pediatric hemophilia patients. Haemophilia. 2004;10(Suppl 3):114.

Chaugule SS, Hay JW, Young G. Understanding patient preferences and willingness to pay for hemophilia therapies. Patient Prefer Adher. 2015;9:1623‐1630. PubMed PMC

Furlan R, Krishnan S, Vietri J. Patient and parent preferences for characteristics of prophylactic treatment in hemophilia. Patient Prefer Adher. 2015;9:1687‐1694. PubMed PMC