Abstrakt
We disagree with the statement made by Ewenstein & Reininger that it is not relevant to study PUPs for the comparison of inhibitor risk between different products. Although the European regulatory agencies have put more focus on studying inhibitor development in previously treated patients (PTPs), there is an ongoing discussion on how PTP and PUP data can complement one another.
Indeed, the European Medicines Agency (EMA) currently recommends PUP studies to investigate efficacy and safety in this patient population and that clinical trial data, addressing efficacy and safety with respect to immunogenicity and other adverse events in all age groups, be generated; guidance was further developed following an increased rate of notifications of inhibitor development in PTPs treated with recombinant FVIII, which gave reason for an expert meeting. The EMA has acknowledged that in daily practice, the most significant and clinically relevant inhibitors may occur in PUPs.
Some haemophilia treaters recommend that investigation of inhibitor development, specifically between PUPs treated with plasma-derived FVIII compared with recombinant FVIII, should be a high priority.