Pharmacogenetic Biomarkers to Predict Treatment Response in Multiple Sclerosis: Current and Future Perspectives.

Abstract

Disease-modifying therapies (DMTs) have significantly advanced the treatment of relapsing multiple sclerosis (MS), decreasing the frequency of relapses, disability, and magnetic resonance imaging lesion formation. However, patients' responses to and tolerability of DMTs vary considerably, creating an unmet need for biomarkers to identify likely responders and/or those who may have treatment-limiting adverse reactions. Most studies in MS have focused on the identification of pharmacogenetic markers, using either the candidate-gene approach, which requires prior knowledge of the genetic marker and its role in the target disease, or genome-wide association, which examines multiple genetic variants, typically single nucleotide polymorphisms (SNPs). Both approaches have implicated numerous alleles and SNPs in response to selected MS DMTs. None have been validated for use in clinical practice. This review covers pharmacogenetic markers in clinical practice in other diseases and then reviews the current status of MS DMT markers (interferon β, glatiramer acetate, and mitoxantrone). For a complex disease such as MS, multiple biomarkers may need to be evaluated simultaneously to identify potential responders. Efforts to identify relevant biomarkers are underway and will need to be expanded to all MS DMTs. These will require extensive validation in large patient groups before they can be used in clinical practice.