Gentherapie der Hämophilie: Empfehlung der Gesellschaft für Thrombose- und Hämostaseforschung (GTH)

Wolfgang Miesbach; Johannes Oldenburg; Robert Klamroth; Hermann Eichler; Jürgen Koscielny; Susanne Holzhauer; Katharina Holstein; Johanna A. Kremer Hovinga; Lorenzo Alberio; Martin Olivieri; Ralf Knöfler; Christoph Male; Andreas Tiede

doi:10.1055/a-1957-4477

Hämostaseologie, Table of Contents

CC BY 4.0 · Hamostaseologie 2023; 43(03): 196-207
DOI: 10.1055/a-1957-4477

Original Article

Gene therapy of Hemophilia: Recommendations from the German, Austrian, and Swiss Society for Thrombosis and Haemostasis Research (GTH)

Article in several languages: deutsch | English

Authors

Wolfgang Miesbach

¹Medizinische Klinik 2, Institut für Transfusionsmedizin, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
Johannes Oldenburg

²Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Medical Faculty, University of Bonn, Bonn, Deutschland
Robert Klamroth

³Klinik für Innere Medizin – Angiologie und Hämostaseologie, Zentrum für Gefäßmedizin, Vivantes Klinikum im Friedrichshain, Berlin, Deutschland
Hermann Eichler

⁴Institut für Klinische Hämostaseologie und Transfusionsmedizin, Universität und Universitätsklinikum des Saarlandes, Homburg/Saar, Deutschland
Jürgen Koscielny

⁵Gerinnungsambulanz mit Hämophiliezentrum, Charité, Berlin, Deutschland
Susanne Holzhauer

⁶Klinik für Pädiatrie m. S. Onkologie und Hämatologie, Charité, Universitätsmedizin, Berlin, Deutschland
Katharina Holstein

⁷II. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
Johanna A. Kremer Hovinga

⁸Universitätsklinik für Hämatologie und Hämatologische Zentrallabor, Universitätsspital Bern, Universität Bern, Bern, Schweiz
Lorenzo Alberio

⁹Division of Haematology and Haematology Central Laboratory, University Hospital of Lausanne (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland
Martin Olivieri

¹⁰Hämophiliezentrum LMU Klinikum - Bereich Pädiatrie, Dr. von Haunerschen Kinderspital, LMU München, München, Deutschland
Ralf Knöfler

¹¹Universitätsklinikum Dresden Klinik/Poliklinik für Kinder- und Jugendmedizin Bereich Hämatologie, Dresden, Deutschland
Christoph Male

¹²Abteilung für Kinder- und Jugendheilkunde, Medizinische Universität Wien, Österreich
Andreas Tiede

¹³Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover, Hannover, Deutschland

Abstract

Gene therapy has recently become a realistic treatment perspective for patients with hemophilia. Reviewing the literature and our personal experience from clinical trials, we discuss key aspects of hemophilia A and B gene therapy with vectors derived from adeno-associated virus, including predictable results, risks, adverse events, and patient-reported outcomes. Patient selection, informed consent, administration, and monitoring of gene therapy as well as data collection are explained. We also discuss the need for interdisciplinary cooperation with hepatology and other specialties. We emphasize structural and organizational requirements for treatment centers according to the hub-and-spoke model and recommend the use of electronic diaries to ensure safe and timely collection and exchange of data. Electronic diaries will play a key role as a primary source of data for pharmacovigilance, postmarketing clinical studies, national and international registries, as well as health technology and benefit assessment. Reimbursement aspects and the future of gene therapy in adolescents and children are also considered. In a rapidly evolving scientific environment, these recommendations aim to support treatment providers and payers to prepare for the implementation of gene therapy following marketing authorization.

Keywords

practice guideline - haemophilia - gene therapy - recommendations - factor VIII - factor IX

Full Text

References

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