Safety of Biological Medicinal Products for Hereditary Coagulopathies: An Analysis of the Russian Pharmacovigilance Database

Abstract

INTRODUCTION. With the expanding product range and the introduction of novel biological medicinal products for haemophilia A, haemophilia B, and von Willebrand disease in the Russian pharmaceutical market, post-marketing safety surveillance becomes especially important.AIM. This study aimed to comprehensively evaluate the data on adverse reactions (ARs) to biological medicinal products for haemophilia A, haemophilia B, and von Willebrand disease reported in the Russian Federation and submitted to the national pharmacovigilance database, with a view to updating the safety data of these medicinal products.MATERIALS AND METHODS. The study analysed spontaneous reports of ARs to medicinal products used as substitution therapy in various types of haemophilia and von Willebrand disease. The analysis focused on spontaneous reports submitted to the Pharmacovigilance database of the Automated Information System of the Russian Federal Service for Surveillance in Healthcare (Roszdravnadzor) in 2019–2023.RESULTS. The analysis identified 126 spontaneous reports documenting 129 ARs associated with biological medicinal products for various types of haemophilia and von Willebrand disease (9 groups of medicinal products according to the Anatomical Therapeutic Chemical (ATC) classification system). The most prolific reporters were pharmaceutical companies (76.2%), whereas healthcare institutions (12.7%) and regional offices of Roszdravnadzor, pharmacovigilance centres, and distributors (11.1%) reported ARs less often. The most frequently reported ARs occurred with emicizumab and medicinal products belonging to the coagulation factor VIII group according to the ATC classification. The most common ARs included haemarthroses, medicinal product ineffectiveness, haemorrhages, and administration site bleeding. Unexpected ARs accounted for 34.1% of cases. The majority of unexpected ARs were haemarthroses, including 5 (31.3%) cases reported with emicizumab and 5 (31.3%) cases associated with octocog alfa (recombinant human coagulation factor VIII). One death was reported with a medicinal product under the International Non-proprietary Name (INN) emicizumab. A comparison of the data obtained in this study with the data available from the international VigiBase database identified spontaneous reports of similar ARs to all the biological medicinal products analysed.CONCLUSIONS. Marketing authorisation holders, manufacturers, and regulatory authorities should continuously monitor the safety of biological medicinal products for the treatment of haemophilia A, haemophilia B, and von Willebrand disease. Prescribing doctors should be vigilant about the haemorrhagic and thrombotic ARs specific to these medicinal products, as well as about potential ineffectiveness, and make timely adjustments to the dose and treatment regimen if necessary.

Keywords

• haemophilia
• von willebrand disease
• emicizumab
• coagulation factor viii
• haemarthrosis
• bleeding
• adverse drug reactions
• drug safety
• pharmacovigilance
• spontaneous reports
• vigibase