Classification of recombinant factor VIII products and implications for clinical practice: A systematic literature review.

INTRODUCTION: Consensus over the definition of recombinant factor VIII (rFVIII) product classification in haemophilia A is lacking. rFVIII products are often classified as standard half-life (SHL) or extended half-life (EHL); despite this, no universally accepted definition currently exists. One proposed definition includes half-life, area under the curve, and technology designed to extend half-life; however, the International Society on Thrombosis and Haemostasis defines activity over time as the most intuitive information for building treatment regimens and the World Federation of Hemophilia describes rFVIII product classification in terms of infusion frequency.

AIM: To summarise published data on the clinical and pharmacokinetic criteria used to define rFVIII product classification.

METHODS: PubMed and EMBASE database searches of English-language articles (2002-2022) were conducted using search strings to identify the relevant population, intervention, and outcomes (e.g., clinical and pharmacokinetic parameters). Articles then underwent title/abstract and full-text screens.

RESULTS: Among 1147 identified articles, 62 were included. Half-life was the most widely reported outcome with no clear trends or product groupings observed. No clear groupings emerged among other outcomes, including infusion frequency, consumption, and efficacy. As activity over time was reported in few articles, further investigation of its relevance to rFVIII product classification is warranted.

CONCLUSION: The findings of this systematic literature review suggest that parameters other than half-life might be important for the development of a comprehensive and clinically relevant rFVIII product classification definition. There seems to be an opportunity to consider parameters that are clinically meaningful and useful for shared decision-making in haemophilia A treatment.