Is long-term administration of interferons in polycythaemia vera associated with risks?

Overview

The treatment of polycythaemia vera and other myeloproliferative disorders with interferons is undergoing a renaissance, primarily for three reasons. Firstly, the duration of action has been extended through pegylation. Secondly, pegylation has improved local tolerance and reduced cytokine release. Thirdly, new and promising evidence has demonstrated efficacy with solid tolerability for pegylated interferons. Different pegylated interferons vary in both their chemical properties and the three-dimensional structure of their positional isomers. Notably, one pegylated interferon –⁠ ropeginterferon a2b –⁠ consists of a single molecule and lacks positional isomers. The isomers of pegylated interferons likely exhibit distinct biological activity, which may contribute to differences in tolerability and the incidence of adverse effects. Two of the largest adverse event databases, the US FAERS and the European EudraVigilance, consistently indicate that there are differences in the incidence and severity of adverse effects among pegylated interferons. Moreover, these differences are corroborated by the findings of controlled phase 2 and phase 3 clinical trials, which, among other outcomes, examined the incidence of early treatment discontinuation due to adverse effects. Based on the analysis of adverse effects and the results of controlled clinical trials, it can be concluded that, for the treatment of polycythaemia vera, ropeginterferon a2b exhibits significantly better tolerability compared with peginterferon a2a and peginterferon a2b across nearly all classes of adverse effects according to the MedDRA classification. Furthermore, a significantly lower proportion of patients undergoing ropeginterferon a2b therapy need to discontinue treatment prematurely due to adverse effects compared with those treated with peginterferon a2a or peginterferon a2b. For clinicians, information on treatment safety is just as crucial as information on clinical efficacy, as this knowledge enables the optimal selection of therapy for each patient.

Keywords:

adverse effects – polycythaemia vera – peginterferon a2a – peginterferon a2b – ropeginterferon a2b – EudraVigilance – FAERS – severity of adverse effects – treatment discontinuation due to adverse effects