Zero incidence of factor VIII inhibitors and successful haemostatic response in previously factor VIII-treated patients with haemophilia A switching to turoctocog alfa in a noninterventional study

Carmen Escuriola Ettingshausen; Olga Katsarou; Barbara Faganel Kotnik; Annie Borel Derlon; Rudolf Schwarz; Paula F Ypma; Irina Matytsina; Sohan Dey; Roger E G Schutgens

doi:10.1111/hae.14454

Zero incidence of factor VIII inhibitors and successful haemostatic response in previously factor VIII-treated patients with haemophilia A switching to turoctocog alfa in a noninterventional study

Haemophilia. 2022 Jan;28(1):46-54. doi: 10.1111/hae.14454. Epub 2021 Nov 17.

Authors

Carmen Escuriola Ettingshausen¹, Olga Katsarou², Barbara Faganel Kotnik³, Annie Borel Derlon⁴, Rudolf Schwarz⁵, Paula F Ypma⁶, Irina Matytsina⁷, Sohan Dey⁸, Roger E G Schutgens⁹

Affiliations

¹ HZRM Hämophilie Zentrum Rhein Main GmbH, Mörfelden-Walldorf, Germany.
² Haemophilia Centre, Laiko Hospital, Athens, Greece.
³ University Children's Hospital, Ljubljana, Slovenia.
⁴ CHU de Caen - Hôpital de la Côte de Nacre, Caen, France.
⁵ Landes Frauen - und Kinderklinik, Linz, Austria.
⁶ Department of Hematology, Hagaziekenhuis, The Hague, The Netherlands.
⁷ Novo Nordisk A/S, Søborg, Denmark.
⁸ Novo Nordisk Service Centre India Private Ltd., Bangalore, India.
⁹ Van Creveldkliniek, University Medical Centre and University, Utrecht, The Netherlands.

Abstract

Introduction: Turoctocog alfa (NovoEight^® ) is a B-domain-truncated recombinant factor VIII (FVIII) approved for patients with haemophilia A.

Aim: To investigate the long-term safety and efficacy of turoctocog alfa in routine clinical practice.

Methods: Guardian 5 was a prospective, multinational, non-interventional, post-authorisation safety study. Male previously treated patients (> 150 exposure days [EDs]) of any age with severe/moderately severe haemophilia A (FVIII ≤ 2%) and a negative inhibitor test prior to first dosing (independent of FVIII-inhibitor history) were included to receive prophylaxis or on-demand treatment. The primary endpoint was the proportion of patients developing FVIII inhibitors (≥.6 Bethesda Units [BU]) after baseline visit, measured as per routine practice of each study site during clinic visits. Secondary endpoints included haemostatic effect, annualised bleeding rate (ABR), and adverse reactions assessment. The study concluded when 50 patients reached 100 EDs/patient minimum.

Results: Seventy patients were screened and 68 exposed to turoctocog alfa; 63 (92.6%) were on prophylaxis and five received on-demand treatment. Six (8.8%) patients reported a history of positive inhibitors. During the study, patients were exposed to turoctocog alfa for a mean (standard deviation) of 131.9 (99.0) days/patient. Fifty-five of 58 patients who completed the study were tested for FVIII inhibitors; no positive tests were reported. Overall success rate of turoctocog alfa for treatment of bleeds was 87.3%. Among patients receiving prophylaxis, median (range) ABR was 1.97 (.0-25.5) bleeds/year; estimated ABR (negative binomial model) was 3.65 (95% confidence interval: 2.53-5.25).

Conclusion: Turoctocog alfa was safe and efficacious for haemophilia A treatment in routine clinical practice.

Keywords: factor VIII inhibitors; haemophilia A; prophylaxis; real-world evidence; recombinant factor VIII; turoctocog alfa.

Publication types

Multicenter Study

MeSH terms

Drug Substitution*
Factor VIII* / therapeutic use
Hemophilia A* / drug therapy
Hemostatics*
Humans
Incidence
Male
Prospective Studies

Substances

Hemostatics
recombinant factor VIII N8
Factor VIII

Grants and funding

Novo Nordisk A/S, Denmark