Disease modifying therapies for relapsing multiple sclerosis

Abstract

Multiple sclerosis (MS) is a common, disabling, putatively autoimmune neurological disease with worldwide distribution. It typically begins as a relapsing disorder that later evolves to a secondary progressive phase. Inflammatory and neurodegenerative mechanisms seem to operate in both phases, but their relative contributions and interactions are incompletely understood. Disease modifying therapies (DMTs) approved for relapsing multiple sclerosis interfere with a variety of immunological mechanisms to reduce rates of relapse, accumulation of disease burden measured by magnetic resonance imaging (MRI), and decline in neurological function over the two to three year duration of typical randomized controlled trials. Benefits of longer duration of therapy on disability are less clear, as data beyond three years are largely limited to observational studies. However, current DMTs do not slow accrual of disability once progressive multiple sclerosis is established. This review summarizes the evidence about the use of approved DMTs and examines how to individualize treatment despite the absence of validated biomarkers to guide drug selection. Methods such as stratifying patients on the basis of estimated risk for future disability, weighing patient specific factors and preferences, and using objective outcomes to adjudicate treatment success are discussed. Emerging drug therapies and strategies are also reviewed.

Disease-modifying therapies for multiple sclerosis

“…There is moderate to high quality evidence from phase III randomised controlled trials and systematic reviews of DMTs 1011. These studies show that DMTs reduce relapses, accumulation of new brain MRI lesions, and disability progression over two to three years in active relapsing multiple sclerosis compared with placebo or an active comparator (interferon beta) 4 Table 2. describes findings of phase III randomised placebo-controlled or active comparator trials of DMTS.…”

“…Relapsing multiple sclerosis— Currently, 15 disease-modifying therapies (DMTs) are licensed for relapsing multiple sclerosis, including five preparations of interferon beta and three preparations of glatiramer acetate 24…”

A novel class of somatic mutations in blood detected preferentially in CD8 + cells

“…> 100 genetic loci are known to be linked with MS predisposition, the overwhelming majority of which are in genes or regions active in leukocytes [9], [10]. The most potent drugs for relapsing MS (natalizumab, alemtuzumab, fingolimod, daclizumab) are mainly targeted against lymphocytes circulating in the blood [11]. Moreover, Epstein-Barr virus (EBV) is a well-documented environmental risk factor of both MS as well as lymphoid and epithelial malignancies, the risk of MS being especially high in association with EBV infectious mononucleosis [12].…”

Multiple Sclerosis Therapies in Pediatric Patients: Challenges and Opportunities

“…The most common adverse effects of mitoxantrone are cardiotoxicity, risk of cardiomyopathy, leukopenia, nausea, infections, alopecia, fatigue, and amenorrhea (37,50,53). There have also been reports of increased risk of colon cancer associated with mitoxantrone (54). Due to the increased risk of cardiotoxicity, it is imperative for patients to undergo frequent echocardiograms, as well as subsequent cardiological tests.…”