Biological monitoring of IFN-β therapy in Multiple Sclerosis

• The different subsets of IFN-β non-responders patients, with a special focus on immuno-pharmacological non-responders, are defined.
• The evaluation of biological activity of IFN-β as a tool for early detection of immuno-pharmacological non-responders is described.
• The characteristics of mRNA MxA as a marker of IFN-β biological activity are underlined.
• The role of IFN-β Nabs in abolishing biological activity and clinical efficacy are described.
• Guidelines and flow-chart to monitor biological activity in MS patients treated with IFN-β are illustrated.

Multiple Sclerosis (MS) is a heterogeneous disease and a variable percentage of patients are non-responders to common treatment. Early diagnosis of non-responders allows change to a more useful therapy for the patient and better allocates a large amount of financial resources. Quantification of Neutralizing antibodies (Nabs) and of biological activity of IFN-β are recognized approaches to identify immuno-pharmacological non-responders. A consistent number of studies have demonstrated that quantification of Myxovirus-induced protein A (MxA) is a valid biomarker to detect immune-pharmacological non responders after one year of treatment. Persistent high titre of Nabs and absence of biological activity predict abolition of IFN-β effects in disease activity measured through MRI, number of relapses and disability. Guidelines and flow-charts including both Nabs and MxA quantification are presented.