Department of Neurology, Ruhr-University Bochum, St. Josef-Hospital, Gudrunstr. 56, 44791, Bochum, Germany.
CNS Drugs. 2022 Aug;36(8):803-817. doi: 10.1007/s40263-022-00939-9. Epub 2022 Jul 22.
Multiple sclerosis treatment made substantial headway during the last two decades with the implementation of therapeutics with new modes of action and routes of application. We are now in the situation that second-generation molecules, approved since 2018, are on the market, characterized by reduced side effects using a more tailored therapeutic approach. Diroximel fumarate is a second-generation fumarate with reduced gastrointestinal side effects. Moreover, several novel, selective, sphingosine-1-phosphate receptor modulators with reduced off-target effects have been developed; namely siponimod, ozanimod, and ponesimod; all oral formulations. B-cell-targeted therapies such as ocrelizumab, given intravenously, and since 2021 ofatumumab, applied subcutaneously, complement the spectrum of novel therapies. The glycoengineered antibody ublituximab is the next anti-CD20 therapy about to be approved. Within the next years, oral inhibitors of Bruton's tyrosine kinase, currently under investigation in several phase III trials, may be licensed for multiple sclerosis. Those developments currently offer an individualized multiple sclerosis therapy, targeting patient needs with substantial effects on relapses, disability progression, and implications for daily life. In this up-to-date review, we provide a holistic overview about novel developments of the therapeutic landscape and upcoming approaches for multiple sclerosis treatment.
多发性硬化症的治疗在过去二十年取得了重大进展,新作用模式和应用途径的治疗方法已经得到实施。我们现在处于第二代分子的市场环境中,自 2018 年以来已经获得批准,这些分子的副作用较小,采用了更具针对性的治疗方法。富马酸二甲酯是一种第二代富马酸,其胃肠道副作用较小。此外,已经开发出几种新型、选择性、鞘氨醇-1-磷酸受体调节剂,其脱靶效应降低;即西尼莫德、奥扎尼莫德和泊尼莫德;均为口服制剂。B 细胞靶向疗法,如静脉注射用奥瑞珠单抗,以及自 2021 年以来皮下应用的奥法妥木单抗,补充了新型疗法的范围。糖基化工程抗体 ublituximab 是下一种即将获得批准的抗 CD20 疗法。在未来几年,几种正在进行的 III 期临床试验中的布鲁顿酪氨酸激酶口服抑制剂可能会获得多发性硬化症的许可。这些进展目前提供了个体化的多发性硬化症治疗方法,针对患者的需求,对复发、残疾进展和日常生活产生重大影响。在这篇最新的综述中,我们全面概述了治疗领域的新进展和多发性硬化症治疗的新方法。