ABSTRACT
Multiple sclerosis (MS) is a complex disease with several mechanisms such as inflammation, demyelination and axonal damage and repair mechanisms contributing sequentially or simultaneously to its pathophysiology. These processes are not uniformly represented across patient populations and can selectively predominate in individual patients. The varying degrees of involvement contribute to the observed heterogeneity in phenotypic expression of the disease, its prognosis and the response to therapies. In analogy to cancer therapy, successful therapeutic strategy in MS might ultimately involve the combination of different therapeutic compounds targeting different disease-relevant processes. Biomarkers, able to characterize and dissect these processes, would be of tremendous value for (1) diagnostics and stratification of subcategories for MS and of disease stages, (2) prediction of disease course, (3) treatment selection and improved prognosis for treatment success and (4) the evaluation of novel therapeutics. Since the approval of immunomodulatory therapies has rendered placebo-controlled trials ethically questionable, trials of novel therapeutics are now conducted as active-arm comparison studies, and are expected to show smaller
treatment effects above and beyond those of the approved therapeutics. This, in turn, leads to a need for larger sample sizes and longer trial duration and, ultimately, cost inflation. Biomarkers are expected to gain increasing importance in the prescreening and evaluation of drugs at the level of phase I/II trials.
