Hamostaseologie 2019; 39(04): 360-367
DOI: 10.1055/s-0039-1698810
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Long-Term Safety and Efficacy Data of a Plasma-Derived Factor VIII Concentrate with von Willebrand Factor for Treatment of Patients with Hemophilia A Covering 18 Years

Sabine Friederike Karolin Kittler
1  Biotest AG, Dreieich, Germany
,
Wolfgang Miesbach
2  Hemophilia Center, Institute of Transfusion Medicine, University Hospital Frankfurt, Frankfurt/Main, Germany
,
Artur Bauhofer
1  Biotest AG, Dreieich, Germany
,
Thomas Becker
1  Biotest AG, Dreieich, Germany
,
Jörg Schüttrumpf
1  Biotest AG, Dreieich, Germany
,
Patrick Dubovy
1  Biotest AG, Dreieich, Germany
,
László Nemes
3  National Hemophilia Center and Hemostasis Department, Medical Center, Hungarian Defence Forces, Budapest, Hungary
,
Heinrich Richter
4  Coagulation Center Muenster, Muenster, Germany
,
Christoph Königs
5  Department of Pediatrics, Hemophilia Center, Goethe University, University Hospital Frankfurt, Frankfurt/Main, Germany
› Author Affiliations
Funding This work was funded by Biotest AG. S.F.K.K, A.B., J.S., and T.B. are employees of Biotest AG. W.M. receives grants and personal fees for lectures and consultancy from Biotest, Bayer, Biogen Idec, CSL Behring, LFB, Novo Nordisk, Octapharma, Pfizer, Roche, Shire, Sobi, and UniQure. L.N. receives personal fees for lectures, organizing education, and consultancy from Bayer, Biotest, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Roche, Shire, and Sobi. H.R. receives grants, travel expenses, and/or personal fees for lectures and consultancy from Biotest, Bayer, Chugai/Roche, CSL Behring, Novo Nordisk, Pfizer, Sobi, and Takeda. C.K. and his institution received funding or personal fees from Bayer, Biotest, CSL Behring, Gilead, Intersero, Jansen, Novo Nordisk, Pfizer, Roche, Shire, Sobi, and the Federal Ministry of Education and Research and the EU (IMI, FP7).
Further Information

Publication History

26 February 2019

21 August 2019

Publication Date:
24 October 2019 (online)

Abstract

We describe the results of the (to our knowledge) longest long-term noninterventional study so far performed to obtain real-life data on the treatment of hemophilia A patients with a single plasma-derived FVIII concentrate containing von Willebrand factor (pdFVIII; Haemoctin/Faktor VIII SDH Intersero). A total of 198 patients (146 in Germany and 52 in Hungary), of whom 160 had severe and 38 nonsevere hemophilia A, representing all age groups (0–88 years; mean ∼25 years at inclusion) were analyzed during prophylactic or on-demand treatment over 18 years (overall 1,418 patient-years; mean >7 years). pdFVIII was very effective and well tolerated. The mean annual bleeding rate, including spontaneous and traumatic bleeds, was considerably lower for patients treated prophylactically (mean 5.4; median 3.1) than for patients treated on demand (mean 26.1; median 21.9). Inhibitors were found in 13% (3/23) and high-titer inhibitors in 4% (1/23) of previously untreated patients with severe hemophilia A. Four previously treated patients with severe hemophilia A developed inhibitors, thereof three high-titer inhibitors (3.3 and 2.5 high-titer inhibitors in 1,000 patient-years). No unexpected adverse effect on the health of the patients, no pdFVIII-related thrombosis, thromboembolic event, or hypersensitivity reaction, and no suspected viral transmission related to pdFVIII were documented.

Zusammenfassung

Wir berichten über die Ergebnisse der unseres Wissens längsten nicht-interventionellen Langzeitstudie mit einem von-Willebrand-Faktor-haltigem humanen FVIII-Konzentrat (pdFVIII, Haemoctin®/Faktor VIII SDH Intersero®) zur Erfassung praxisnaher Daten aus der alltäglichen Therapie von Patienten mit einer Hämophilie A. 198 Patienten (146 in Deutschland und 52 in Ungarn) aller Altersgruppen (0–88 Jahre; durchschnittlich ∼25 Jahre alt beim Einschluss), 160 davon mit schwerer und 38 mit nicht schwerer Hämophilie A, wurden im Rahmen ihrer prophylaktischen oder Bedarfstherapie über 18 Jahre analysiert (insgesamt 1418 Patientenjahre; durchschnittlich >7 Jahre). Der pdFVIII erwies sich als sehr wirksam und verträglich. Die durchschnittliche jährliche Blutungsrate (spontane und traumatische Blutungen) war deutlich geringer in Patienten, die prophylaktisch (Mittelwert 5,4; Median 3,1) anstatt bei Bedarf (Mittelwert 26,1; Median 21,9) mit pdFVIII behandelt wurden. Inhibitoren wurden in 13% (3/23) und hochtitrige in 4% (1/23) der zuvor unbehandelten Patienten mit schwerer Hämophilie A dokumentiert. Vier der vorbehandelten Patienten mit schwerer Hämophilie A entwickelten Inhibitoren, 3 davon hochtitrige (3.3 Inhibitoren und 2.5 hochtitrige pro 1000 Patientenjahren). Während der Langzeittherapie mit pdFVIII wurde kein unerwünschter Einfluss auf den allgemeinen Gesundheitszustand der Patienten festgestellt. Es trat keine thromboembolische Reaktion, keine Überempfindlichkeitsreaktion, und keine Virusübertragung im kausalen Zusammenhang mit pdFVIII auf.

Authors' Contributions

L.N. and C.K. contributed with a significant number of patients to this NIS. A.B. and T.B. designed the Biotest NIS. A.B., J.S., T.B., and S.F.K.K. performed the research. P.D. was responsible for data management and provided statistical support. S.F.K.K., A.B., T.B., and J.S. analyzed the data. The main writing was done by S.F.K.K. Analyses were discussed with W.M., C.K., H.R., and L.N.

All authors reviewed and approved the final manuscript.


Supplementary Material