Multiple Sclerosis: Current and Emerging Disease-Modifying Therapies and Treatment Strategies

Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating central nervous system disease that typically strikes young adults, especially women. The pathobiology of MS includes inflammatory and neurodegenerative mechanisms that affect both white and gray matter. These mechanisms underlie the relapsing, and often eventually progressive, course of MS, which is heterogeneous; confident prediction of long-term individual prognosis is not yet possible. However, because revised MS diagnostic criteria that incorporate neuroimaging data facilitate early diagnosis, most patients are faced with making important long-term treatment decisions, most notably the use and selection of disease-modifying therapy (DMT). Currently, there are 10 approved MS DMTs with varying degrees of efficacy for reducing relapse risk and preserving neurological function, but their long-term benefits remain unclear. Moreover, available DMTs differ with respect to the route and frequency of administration, tolerability and likelihood of treatment adherence, common adverse effects, risk of major toxicity, and pregnancy-related risks. Thorough understanding of the benefit-risk profiles of these therapies is necessary to establish logical and safe treatment plans for individuals with MS. We review the available evidence supporting risk-benefit profiles for available and emerging DMTs. We also assess the place of individual DMTs within the context of several different MS management strategies, including those currently in use (sequential monotherapy, escalation therapy, and induction and maintenance therapy) and others that may soon become feasible (combination approaches and "personalized medicine"). We conducted this review using a comprehensive search of MEDLINE, PubMed, EMBASE, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials, from January 1, 1990, to August 31, 2013. The following search terms were used: multiple sclerosis, randomized controlled trials, interferon-beta, glatiramer acetate, mitoxantrone, natalizumab, fingolimod, teriflunomide, dimethyl fumarate, BG-12, alemtuzumab, rituximab, ocrelizumab, daclizumab, neutralizing antibodies, progressive multifocal leukoencephalopathy.

Predictors of response to opicinumab in acute optic neuritis

“…Therapies enhancing remyelination and thus supporting axonal integrity and function remain an unmet need for demyelinating diseases such as AON and MS 6. Opicinumab (anti‐LINGO‐1, BIIB033) is a human monoclonal antibody against leucine‐rich repeat and immunoglobulin‐like domain‐containing protein 1 (LINGO‐1; an oligodendrocyte differentiation and myelination suppressor) that was genetically engineered to reduce immunoglobulin effector function.…”

Stem Cell Therapy: A Promising Therapeutic Approach for Multiple Sclerosis

“…Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system (CNS) and leads to demyelination of neural fibers, severe neurological symptoms, and progressive disability (1,2). None of the currently available drugs are effective in supporting regeneration of the demyelinated areas, and preventing disease progression (2).…”

“…None of the currently available drugs are effective in supporting regeneration of the demyelinated areas, and preventing disease progression (2). Stem cells, because of their self-renewal and differentiation capacity into various cell types, appear to be suitable candidates for alternative therapeutic strategies for MS (3,4).…”

[Budget impact analysis of delayed-release dimethyl-fumarate in the treatment of relapsing-remitting multiple sclerosis in Italy]

“…L'introduzione di natalizumab e fingolimod ha offerto una nuova opportunità terapeutica ai pazienti SMRR ad alta attività di malattia, o ai pazienti non-responder ai DMT iniettabili di prima linea [8][9][10]. La recente introduzione di nuove terapie orali (dimetilfumarato a rilascio ritardato anche conosciuto come dimetil-fumarato gastroresistente, d'ora in avanti dimetil-fumarato, e teriflunomide) consente al medico neurologo ulteriori opzioni di scelta per il raggiungimento degli obiettivi terapeutici [11][12][13]. Dimetil-fumarato in data 30 gennaio 2014 è stato approvato dalla Commissione Europea con l'indicazione: "Trattamento dei pazienti adulti con sclerosi multipla recidivante remittente" [14] e successivamente rimborsato dall'Agenzia Italiana del Farmaco (AIFA) [15] in classe A, nota 65 (GU n.19 del 24/01/2015).…”