シンポジウム7：多発性硬化症の治療現状
多発性硬化症治療薬の理解と選択
キーワード:
multiple sclerosis,
disease–modifying drug,
baseline drug,
escalation therapy,
induction therapy
2018 年 35 巻 4 号 p. 499-503
詳細
2018 年 35 巻 4 号 p. 499-503
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) and the pathogenesis leading to demyelination includes 3 major processes. The first step is establishment of autoimmunity to CNS myelin components. The second step is entry of immune cells into the CNS via the blood–brain barrier (BBB). Activated T cells can easily cross the BBB using surface α4–integrin as a ligand to VCAM–1, which is expressed on endothelial cells in the CNS. As the third step, immune reactions occur within the CNS when activated T cells encounter specific antigens presented by microglia. Of the helper T cells re–stimulated by autoantigens, Th1 cells producing interferon–γ and Th17 cells secreting interleukin–17 play major roles in propagating inflammation, while Th2 cells producing IL–4, and regulatory T cells secreting IL–10 and TGF–β suppress pathological processes. Final demyelination is rendered either by macrophages recruited from the bloodstream across the BBB, or by TNF–α and nitric oxide, which are secreted by Th1 cells and macrophages, and toxic to CNS myelin. With these immunopathgenesis of MS in mind, physicians should decide to choose one among the 6 disease–modifying drugs (DMDs), including interferon–β1b, interferon–β1a, glatiramer acetate, fingolimod, natalizumab, and dimethyl fumarate. The first 3 drugs are regarded as a baseline one preventing disease activation through Th2–predominant immune effect (Th2 shift) with long–term safety profile. Fingolimod and natalizumab render more potent suppression to MS via marked reduction of immune cells entering the CNS. The former is placed as second–line drug as is the latter for JC virus–negative patients, while natalizumab for JC virus–infected patients is placed in the third, because of the risk for the development of progressive multifocal leukoencephalopathy. The position of dimethyl fumarate has not been established. Usually, escalation therapy is chosen, however, induction therapy may be necessary for patients with highly active disease. Physicians should obtain informed consent from patients with MS after full explanation of risk and benefit of those DMDs.
