MxA mRNA decrease preceding NAb detection in IFNβ‐treated MS patients

BACKGROUND Multiple sclerosis (MS) patients treated with interferon beta (IFNβ) are at risk of a declining response to treatment because of the production of IFNβ-neutralizing antibodies (NAbs). The expression of Myxovirus resistance protein A (MxA) mRNA is regarded as a marker of IFNβ bioactivity. AIMS The aim of this study was to analyze the kinetics of MxA mRNA expression during long-term IFNβ treatment and assess its relationship to NAb production. METHODS A prospective, observational, open-label, non-randomized study was designed in multiple sclerosis patients starting IFNβ treatment. NAbs and MxA mRNA were monitored every six months. RESULTS 119 patients were consecutively enrolled and 107 were included in the final analysis. Both the presence of NAbs and a decrease in MxA mRNA below the cut off were revealed in 15 patients, however, in six patients (40%) positivity for NAbs was preceded by the decrease in MxA mRNA. In addition, a further six patients showing a decline in MxA mRNA did not have detectable NAbs. CONCLUSION Our data indicate that quantification of MxA mRNA is a more sensitive identifier of loss of IFNβ efficacy than the NAb positivity.