Biomarkers of treatment response in multiple sclerosis

Abstract

Multiple sclerosis (MS) is considered a heterogeneous disease with respect to disease progression and treatment response, which have both remained highly unpredictable. With an increasing number of available disease modifying therapies, strategies for treatment allocation in the individual patient or subgroup of patients has become more important. Therefore biomarkers, which will identify subgroups of MS patients and predict treatment response early in the course of the disease, are urgently needed. Here we review current and emerging biomarkers, as well as study concepts for identification of new biomarkers in MS.

Keywords::

• biomarker
• multiple sclerosis
• treatment response

Financial & competing interests disclosure

This work was supported by a grant from the German Ministry for Education and Research (BMBF, ‘German Competence Network Multiple Sclerosis’ (KKNMS), Control-MS, 01GI0917). D Buck has received compensation for activities with Bayer HealthCare, BiogenIdec, MerckSerono and Novartis. D Buck was supported by the Commission for Clinical Research of the Faculty of Medicine, Technical University Munich, Abirisk and the PML Consortium. B Hemmer has received compensation for serving as a scientific advisor and speaker for Hoffmann la Roche, MerckSerono, BiogenIdec, Novartis and Bayer. B Hemmer has served as a consultant for Gerson Lehrman Group. B Hemmer has received grant support for research projects from Novartis, BiogenIdec, MerckSerono, Bayer, Metanomics, Protagen AG, 5-prime, Roche, Chugai, Deutsche Forschungsgemeinschaft (DFG), Bundesministerium für Bildung und Forschung (BMBF) and Hertie Foundation. B Hemmer holds a patent on KIR4.1 antibody testing in MS. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Multiple sclerosis is a heterogeneous disease with respect to disease progression and treatment response. Therefore, biomarkers are needed to stratify patients with respect to individual prognosis and treatment response.

• Treatment response of disease-modifying therapies includes disease activity, side effects and adherence to therapy.

• Clear definitions of ‘responders,’ ‘partial responder’ and ‘nonresponder’ in clinical trials are needed.

• High-quality biobanking is a prerequisite for the discovery of biomarkers.

• Large and well-defined cohorts of patients are needed for successful biomarker discovery and validation.

• MRI is an established and optical coherence tomography is a promising imaging tool to measure disease activity and response to therapy.

• Intense research on antibody biomarkers in multiple sclerosis is ongoing.

• Cerebrospinal fluid biomarkers might be helpful for initial stratification of patients with respect to disease progression.

• Antidrug antibodies are a biomarker of treatment failure.

• Anti-JC virus antibodies are a biomarker of treatment adverse event.

• New technologies in the field of genomics, epigenomics, transcriptomics, proteomics and metabolomics will facilitate the discovery of new biomarkers.