Disease-modifying drugs in multiple sclerosis: new oral options

Milena De Riz, Daniela Galimberti and Elio Scarpini

Multiple sclerosis is characterized by multifocal CNS lesions with perivenular inflammation, demyelination, axonal transection, neuronal degeneration and gliosis. Proinflammatory CD4+ and CD8+ T cells reactive to CNS myelin antigens mediate the initial phases of lesion formation. Other T‑cell subsets, B cells, monocyte-macrophages and natural killer cells have been implicated in both effector and regulatory mechanisms. Inflammatory processes predominate in early disease, whereas progression of neurological disability reflects neurodegeneration. A number of disease-modifying drugs with immunomodulatory (e.g., IFN‑b, glatiramer acetate and natalizumab) or immunosuppressant properties (e.g., mithoxantron) have been employed over the past two decades, in order to reduce the relapse rate. Unfortunately, they are limited by parenteral use. Recently, some new oral compounds have been developed reaching similar or higher control of disease activity, improving quality of life and increasing adherence. In this article, an update of main emerging oral disease-modifying drugs will be provided, including clinical trials design, mechanisms of action and safety aspects.