Mellen Center for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic, 9500 Euclid Ave, U-10, Cleveland, OH, 44195, USA.
Drugs. 2018 Oct;78(15):1549-1566. doi: 10.1007/s40265-018-0984-5.
Despite the fact that majority of patients with multiple sclerosis (MS) have relapsing-remitting disease, many transition to secondary progressive disease (SPMS) over time. This transition is thought to be related to neurodegenerative processes increasingly predominating over inflammatory processes as the driving forces of disability. However, some patients initially present with primary progressive disease (PPMS) that is characterized by a gradual accumulation of neurological symptoms and subsequent disability accumulation. The treatment of both PPMS and SPMS, collectively referred to as progressive MS, has proven quite challenging due to the multifactorial and poorly understood pathophysiology of multiple sclerosis in general, specifically that of progressive disease. The purpose of this article is to discuss important clinical and pathophysiologic differences between relapsing and progressive forms of MS, review previous notable trials of drugs in progressive MS, examine current literature regarding recent and promising progressive MS treatments, and discuss future considerations for progressive MS therapeutics and management. Specifically, the current evidence regarding treatment of progressive MS with ocrelizumab, simvastatin, ibudilast, alpha-lipoic acid, high-dose biotin, siponimod, and cell-based therapies are discussed.
尽管大多数多发性硬化症 (MS) 患者的疾病表现为复发缓解型，但随着时间的推移，许多患者会逐渐进展为继发进展型疾病 (SPMS)。这种转变被认为与神经退行性过程逐渐超过炎症过程，成为残疾的主要驱动因素有关。然而，有些患者最初表现为原发性进展型疾病 (PPMS)，其特征是神经症状逐渐积累，随后残疾逐渐积累。由于多发性硬化症的病理生理学通常具有多因素且难以理解的特点，特别是进展型疾病，因此 PPMS 和 SPMS 的治疗都极具挑战性。本文旨在讨论复发型和进展型 MS 之间重要的临床和病理生理学差异，回顾先前在进展型 MS 中进行的重要药物试验，研究最近关于有前途的进展型 MS 治疗方法的文献，并讨论进展型 MS 治疗和管理的未来考虑因素。具体而言，本文将讨论目前关于用奥瑞珠单抗、辛伐他汀、依度沙班、硫辛酸、生物素高剂量、西尼莫德和细胞疗法治疗进展型 MS 的证据。
