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

Background: Prolonged therapy with interferon beta ( IFN beta) often leads to the development of anti-IFN beta binding antibodies ( BAbs). A subset of the BAbs is of a neutralizing nature ( neutralizing antibodies, NAbs) and is associated with reduced clinical efficacy of therapy. Myxovirus-resistance-protein A (MxA) has proven to be a reliable biomarker of IFN beta bioactivity. We analyzed the prognostic value of MxA mRNA, NAbs, and BAbs on the risk of having a new relapse in IFN beta-treated patients. Methods: A 3-year study was conducted in 137 IFN beta-treated patients. Blood samples for BAbs, NAbs, and MxA mRNA measurements were taken after 12 +/- 3 months of therapy. Analysis of relapse-free survival ( RFS) was performed for all measures by using known thresholds, generating positive and negative groups. Also, time between sampling and following relapse and risk of new relapses were calculated. Results: The MxA-negative group showed poorer RFS rates than the MxA-positive group [ p < 0.0001, hazard ratio ( HR) = 2.87]. Likewise, the NAb-positive group showed poorer RFS rates than the NAb-negative group ( p = 0.0013; HR = 2.49). On the contrary, BAb measurement did not show a clear clinical significance. Conclusions: 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.