Ciotti John Robert, Cross Anne Haney
Washington University in St. Louis, St. Louis, MO, USA.
, St. Louis, USA.
Curr Treat Options Neurol. 2018 Apr 7;20(5):12. doi: 10.1007/s11940-018-0496-3.
Multiple sclerosis (MS) is an immune-mediated disorder that affects the central nervous system (CNS), often first affecting people in early adulthood. Although most MS patients have a relapsing-remitting course (RRMS) at disease onset, a substantial proportion later develop chronic progression, termed secondary progressive MS (SPMS). Approximately 10% of MS patients experience chronic progression from disease onset, termed primary progressive multiple sclerosis (PPMS). Although several disease-modifying treatment (DMT) options exist for relapsing forms of this disease, DMT options are few for progressive MS (PPMS and SPMS). Herein, we strive to define progressive MS, review major clinical trials aimed at progressive MS, and delineate potential strategies in the management of progressive MS.
In 2017, the first DMT for PPMS, the B lymphocyte-depleting monoclonal antibody, ocrelizumab, came to market. Ocrelizumab reduced 12-week confirmed disability progression (CDP) by 24% versus placebo. Siponimod, a selective sphingosine-1-phosphate receptor modulator, reduced 3-month CDP by 21% versus placebo in SPMS. Ibudilast slowed brain atrophy in PPMS and SPMS patients in a multicenter phase 2b study. Smaller early phase studies of alpha-lipoic acid and simvastatin each found slowing of rate of whole brain atrophy in SPMS patients. Reasons now exist for optimism in the search for DMTs for progressive MS. It remains a challenge to identify outcome measures that accurately reflect the underlying pathology in progressive MS, which is less inflammatory and more degenerative than RRMS.
多发性硬化症（MS）是一种影响中枢神经系统（CNS）的免疫介导性疾病，通常在成年早期首次发病。尽管大多数MS患者在疾病发作时具有复发缓解型病程（RRMS），但相当一部分患者后来会发展为慢性进展型，称为继发进展型MS（SPMS）。约10%的MS患者从疾病发作起就经历慢性进展，称为原发进展型多发性硬化症（PPMS）。尽管对于这种疾病的复发形式存在几种疾病修正治疗（DMT）选择，但对于进展型MS（PPMS和SPMS），DMT选择很少。在此，我们努力定义进展型MS，回顾针对进展型MS的主要临床试验，并阐述进展型MS管理中的潜在策略。
2017年，首个用于PPMS的DMT，即B淋巴细胞清除单克隆抗体奥瑞珠单抗上市。与安慰剂相比，奥瑞珠单抗使12周确认的残疾进展（CDP）降低了24%。西尼莫德是一种选择性鞘氨醇-1-磷酸受体调节剂，在SPMS中与安慰剂相比使3个月的CDP降低了21%。在一项多中心2b期研究中，异丁司特减缓了PPMS和SPMS患者的脑萎缩。关于α-硫辛酸和辛伐他汀的较小规模早期研究均发现SPMS患者全脑萎缩率减缓。现在在寻找进展型MS的DMT方面有理由感到乐观。确定准确反映进展型MS潜在病理的结局指标仍然是一项挑战，进展型MS比RRMS炎症性更低且退行性更强。
