Predictive markers for response to interferon therapy in patients with multiple sclerosis

Abstract

Findings indicate that measurements of both myxovirus-resistance-protein A (MxA) and neutralizing antibodies (NAbs) predict the risk of new relapses; however, the slightly stronger prognostic significance of MxA mRNA and the easier method for it measurement make MxA mRNA the preferred biomarker for monitoring interferon beta (IFN beta)-treated patients. This information can be used to better tailor treatment to the individual patient with MS.

One-year evaluation of factors affecting the biological activity of interferon beta in multiple sclerosis patients

“…MxA gene expression levels above or below 87 RE correctly predicted the response to IFNb injection with a sensitivity of 92.44% and a specificity of 92.52%. The MxA mRNA threshold of 87 RE has recently been clinically validated and was shown to have a strong prognostic value for the risk of new relapses [1].…”

“…Their identification can be made after 1 year of treatment, allowing for the utilization of alternative agents and saving huge amount of economical resources. In fact, a large number of papers have demonstrated that measurement of MxA is a reliable, easy to perform, pharmacogenomic marker of IFNb biological activity, and recently of clinical efficacy [1].…”

“…MxA show an increased level in patients after the first IFNb injection [2,3], whereas in a relevant percentage of patients during IFNb therapy, MxA expression is inhibited, mainly due to the development of BAbs and/or NAbs [1,2,[4][5][6][7][8][9][10][11][12][13][14][15][16]. On these grounds, MxA can be considered a biomarker intended to substitute for clinical endpoint, i.e., a surrogate endpoint.…”

“…In this study we evaluate IFNb biological activity after 1 year of treatment in order to (1) to classify patients according to MxA expression level, (2) to identify pharmacogenomic non responders, (3) to analyze the causes of MxA expression abolition.…”

Therapeutic options in multiple sclerosis

“…27 Another potential marker of biologic response to interferon therapy is the presence of myxovirus-resistance protein A (MxA), an antiviral protein exclusively induced by type 1 interferons. 28 Quantification of MxA expression might be a sensitive measure of IFN␤ activity.…”