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中山大学附属第三医院神经内科,广州 510630
王 茜,Email:wx013100@163.com, 研究方向:中枢神经系统脱髓鞘疾病。
李 蕊,Email:lirui55@mail.sysu.edu.cn。
收稿:2024-01-20,
修回:2024-02-27,
录用:2024-02-29,
纸质出版:2024-05-28
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王茜,陆正齐,李蕊.多发性硬化的治疗进展[J].重庆医科大学学报,2024,49(5):597-602.
Wang Xi,Lu Zhengqi,Li Rui.Advances in the treatment of multiple sclerosis[J].Journal of Chongqing Medical University,2024,49(5):597-602.
王茜,陆正齐,李蕊.多发性硬化的治疗进展[J].重庆医科大学学报,2024,49(5):597-602. DOI: 10.13406/j.cnki.cyxb.003500.
Wang Xi,Lu Zhengqi,Li Rui.Advances in the treatment of multiple sclerosis[J].Journal of Chongqing Medical University,2024,49(5):597-602. DOI: 10.13406/j.cnki.cyxb.003500.
多发性硬化(multiple sclerosis,MS)是一种慢性中枢神经系统炎症性脱髓鞘疾病,随着人们对MS发病机制了解的深入,MS的治疗手段也在不断更新。近年来,新上市的疾病修饰治疗(disease-modifying therapy,DMT)药物层出不穷,临床研究显示出良好的疗效及安全性。治疗策略及目标也在更新。本文主要对近年来新上市的DMT药物的作用机制、疗效以及安全性进行综述,此外对治疗策略、治疗目标以及正在研发的新药也做了简要介绍,以期为临床决策的制定提供参考。
Multiple sclerosis(MS) is a chronic inflammatory demyelinating disease of the central nervous system. As our understanding of the pathogenesis of MS gradually deepens, the treatment methods for MS are being constantly updated. In recent years,a large number of disease-modifying therapy(DMT) drugs have been introduced,and clinical studies have shown that such drugs have good efficacy and safety. Treatment strategies and goals are also being improved. This article mainly reviews the mechanism of action,efficacy, and safety of the DMT drugs introduced in recent years and briefly introduces treatment strategies,treatment goals,and new drugs under development,in order to provide a reference for clinical decision-making.
中华医学会神经病学分会神经免疫学组 . 多发性硬化诊断与治疗中国指南(2023版) [J ] . 中华神经科杂志 , 2024 , 57 ( 1 ): 10 - 23 .
Chinese Society of Neuroimmunology . Chinese guidelines for diagnosis and treatment of multiple sclerosis(2023 edition) [J ] . Chin J Neurol , 2024 , 57 ( 1 ): 10 - 23 .
吴云斐 , 李寿林 , 谢 杰 . 甲泼尼龙鞘内注射对急性期多发性硬化患者神经功能及免疫功能的影响 [J ] . 解放军医药杂志 , 2022 , 34 ( 6 ): 118 - 121 .
Wu YF , Li SL , Xie J . Effects of intrathecal injection of methylprednisolone on neurological and immune functions in patients with acute multiple sclerosis [J ] . Med Pharm J Chin People's Liberation Army , 2022 , 34 ( 6 ): 118 - 121 .
毕 峰 , 杨明妍 , 吴雪姣 . 鞘内给药对急性期多发性硬化患者的影响 [J ] . 中国医药科学 , 2023 , 13 ( 12 ): 137 - 140 .
Bi F , Yang MY , Wu XJ . Impact of intrathecal administration on patients with acute multiple sclerosis [J ] . China Med Pharm , 2023 , 13 ( 12 ): 137 - 140 .
Stamatellos VP , Papazisis G . Safety and monitoring of the treatment with disease-modifying therapies(DMTs) for multiple sclerosis (MS) [J ] . Curr Rev Clin Exp Pharmacol , 2023 , 18 ( 1 ): 39 - 50 .
Cohan SL , Benedict RHB , Cree BAC , et al . The two sides of siponimod:evidence for brain and immune mechanisms in multiple sclerosis [J ] . CNS Drugs , 2022 , 36 ( 7 ): 703 - 719 .
Kappos L , Bar-Or A , Cree BAC , et al . Siponimod versus placebo in secondary progressive multiple sclerosis(EXPAND):a double-blind,randomised,phase 3 study [J ] . Lancet , 2018 , 391 ( 10127 ): 1263 - 1273 .
Comi G , Kappos L , Selmaj KW , et al . Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis(SUNBEAM):a multicentre,randomised,minimum 12-month,phase 3 trial [J ] . Lancet Neurol , 2019 , 18 ( 11 ): 1009 - 1020 .
Cree BA , Selmaj KW , Steinman L , et al . Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis:up to 5 years of follow-up in the DAYBREAK open-label extension trial [J ] . Mult Scler , 2022 , 28 ( 12 ): 1944 - 1962 .
Cohen JA , Arnold DL , Comi G , et al . Safety and efficacy of the selective sphingosine 1-phosphate receptor modulator ozanimod in relapsing multiple sclerosis(RADIANCE):a randomised,placebo-controlled,phase 2 trial [J ] . Lancet Neurol , 2016 , 15 ( 4 ): 373 - 381 .
Pérez-Jeldres T , Alvarez-Lobos M , Rivera-Nieves J . Targeting sphingosine-1-phosphate signaling in immune-mediated diseases:beyond multiple sclerosis [J ] . Drugs , 2021 , 81 ( 9 ): 985 - 1002 .
Freedman MS , Pozzilli C , Havrdova EK , et al . Long-term treatment with ponesimod in relapsing-remitting multiple sclerosis:results from randomized phase 2b core and extension studies [J ] . Neurology , 2022 , 99 ( 8 ): e762 - e774 .
Kappos L , Fox RJ , Burcklen M , et al . Ponesimod compared with teriflunomide in patients with relapsing multiple sclerosis in the active-comparator phase 3 OPTIMUM study:a randomized clinical trial [J ] . JAMA Neurol , 2021 , 78 ( 5 ): 558 - 567 .
Swallow E , Pham T , Patterson-Lomba O , et al . Comparative efficacy and safety of ozanimod and ponesimod for relapsing multiple sclerosis:a matching-adjusted indirect comparison [J ] . Mult Scler Relat Disord , 2023 , 71 : 104551 .
Jacobs BM , Ammoscato F , Giovannoni G , et al . Cladribine:mechanisms and mysteries in multiple sclerosis [J ] . J Neurol Neurosurg Psychiatry , 2018 , 89 ( 12 ): 1266 - 1271 .
Giovannoni G , Comi G , Cook S , et al . A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis [J ] . N Engl J Med , 2010 , 362 ( 5 ): 416 - 426 .
Dubey D , Kieseier BC , Hartung HP , et al . Dimethyl fumarate in relapsing-remitting multiple sclerosis:rationale,mechanisms of action,pharmacokinetics,efficacy and safety [J ] . Expert Rev Neurother , 2015 , 15 ( 4 ): 339 - 346 .
Gold R , Kappos L , Arnold DL , et al . Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis [J ] . N Engl J Med , 2012 , 367 ( 12 ): 1098 - 1107 .
Fox RJ , Miller DH , Phillips JT , et al . Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis [J ] . N Engl J Med , 2012 , 367 ( 12 ): 1087 - 1097 .
Naismith RT , Wolinsky JS , Wundes A , et al . Diroximel fumarate (DRF) in patients with relapsing-remitting multiple sclerosis:interim safety and efficacy results from the phase 3 EVOLVE-MS-1 study [J ] . Mult Scler , 2020 , 26 ( 13 ): 1729 - 1739 .
Naismith RT , Wundes A , Ziemssen T , et al . Diroximel fumarate demonstrates an improved gastrointestinal tolerability profile compared with dimethyl fumarate in patients with relapsing-remitting multiple sclerosis:results from the randomized,double-blind,phase ⅢEVOLVE-MS-2 study [J ] . CNS Drugs , 2020 , 34 ( 2 ): 185 - 196 .
Berger AA , Sottosanti ER , Winnick A , et al . Monomethyl fumarate (MMF,bafiertam) for the treatment of relapsing forms of multiple sclerosis (MS) [J ] . Neurol Int , 2021 , 13 ( 2 ): 207 - 223 .
Wynn D , Lategan TW , Sprague TN , et al . Monomethyl fumarate has better gastrointestinal tolerability profile compared with dimethyl fumarate [J ] . Mult Scler Relat Disord , 2020 , 45 : 102335 .
Hauser SL , Bar-Or A , Cohen JA , et al . Ofatumumab versus teriflunomide in multiple sclerosis [J ] . N Engl J Med , 2020 , 383 ( 6 ): 546 - 557 .
Hauser SL , Cross AH , Winthrop K , et al . Safety experience with continued exposure to ofatumumab in patients with relapsing forms of multiple sclerosis for up to 3.5 years [J ] . Mult Scler , 2022 , 28 ( 10 ): 1576 - 1590 .
Montalban X , Gold R , Thompson AJ , et al . ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis [J ] . Eur J Neurol , 2018 , 25 ( 2 ): 215 - 237 .
Montalban X , Hauser SL , Kappos L , et al . Ocrelizumab versus placebo in primary progressive multiple sclerosis [J ] . N Engl J Med , 2017 , 376 ( 3 ): 209 - 220 .
Hauser SL , Bar-Or A , Comi G , et al . Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis [J ] . N Engl J Med , 2017 , 376 ( 3 ): 221 - 234 .
Hauser SL , Kappos L , Arnold DL , et al . Five years of ocrelizumab in relapsing multiple sclerosis:opera studies open-label extension [J ] . Neurology , 2020 , 95 ( 13 ): e1854 - e1867 .
Rommer PS , Eichstädt K , Ellenberger D , et al . Symptomatology and symptomatic treatment in multiple sclerosis:results from a nationwide MS registry [J ] . Mult Scler , 2019 , 25 ( 12 ): 1641 - 1652 .
Filippini G , Minozzi S , Borrelli F , et al . Cannabis and cannabinoids for symptomatic treatment for people with multiple sclerosis [J ] . Cochrane Database Syst Rev , 2022 , 5 ( 5 ): CD013444 .
Nicholas J , Lublin F , Klineova S , et al . Efficacy of nabiximols oromucosal spray on spasticity in people with multiple sclerosis:treatment effects on spasticity numeric rating scale,muscle spasm count,and spastic muscle tone in two randomized clinical trials [J ] . Mult Scler Relat Disord , 2023 , 75 : 104745 .
Vecchio M , Chiaramonte R , di Benedetto P . Management of bladder dysfunction in multiple sclerosis:a systematic review and meta-analysis of studies regarding bladder rehabilitation [J ] . Eur J Phys Rehabil Med , 2022 , 58 ( 3 ): 387 - 396 .
Rahnama'i MS . Neuromodulation for functional bladder disorders in patients with multiple sclerosis [J ] . Mult Scler , 2020 , 26 ( 11 ): 1274 - 1280 .
Vasileiou ES , Fitzgerald KC . Multiple sclerosis pathogenesis and updates in targeted therapeutic approaches [J ] . Curr Allergy Asthma Rep , 2023 , 23 ( 9 ): 481 - 496 .
Reich DS , Arnold DL , Vermersch P , et al . Safety and efficacy of tolebrutinib,an oral brain-penetrant BTK inhibitor,in relapsing multiple sclerosis:a phase 2b,randomised,double-blind,placebo-controlled trial [J ] . Lancet Neurol , 2021 , 20 ( 9 ): 729 - 738 .
Montalban X , Arnold DL , Weber MS , et al . Placebo-controlled trial of an oral BTK inhibitor in multiple sclerosis [J ] . N Engl J Med , 2019 , 380 ( 25 ): 2406 - 2417 .
Vermersch P , Brieva-Ruiz L , Fox RJ , et al . Efficacy and safety of masitinib in progressive forms of multiple sclerosis:a randomized,phase 3,clinical trial [J ] . Neurol Neuroimmunol Neuroinflamm , 2022 , 9 ( 3 ): e1148 .
Boffa G , Signori A , Massacesi L , et al . Hematopoietic stem cell transplantation in people with active secondary progressive multiple sclerosis [J ] . Neurology , 2023 , 100 ( 11 ): e1109 - e1122 .
Genchi A , Brambilla E , Sangalli F , et al . Neural stem cell transplantation in patients with progressive multiple sclerosis:an open-label,phase 1 study [J ] . Nat Med , 2023 , 29 ( 1 ): 75 - 85 .
Sapko K , Jamroz-Wiśniewska A , Rejdak K . Novel drugs in a pipeline for progressive multiple sclerosis [J ] . J Clin Med , 2022 , 11 ( 12 ): 3342 .
Havla J , Hohlfeld R . Antibody therapies for progressive multiple sclerosis and for promoting repair [J ] . Neurotherapeutics , 2022 , 19 ( 3 ): 774 - 784 .
Oh J , Bar-Or A . Emerging therapies to target CNS pathophysiology in multiple sclerosis [J ] . Nat Rev Neurol , 2022 , 18 ( 8 ): 466 - 475 .
Harding K , Williams O , Willis M , et al . Clinical outcomes of escalation vs early intensive disease-modifying therapy in patients with multiple sclerosis [J ] . JAMA Neurol , 2019 , 76 ( 5 ): 536 - 541 .
Rojas JI , Patrucco L , Alonso R , et al . Effectiveness and safety of early high-efficacy versus escalation therapy in relapsing-remitting multiple sclerosis in Argentina [J ] . Clin Neuropharmacol , 2022 , 45 ( 3 ): 45 - 51 .
Filippi M , Amato MP , Centonze D , et al . Early use of high-efficacy disease-modifying therapies makes the difference in people with multiple sclerosis:an expert opinion [J ] . J Neurol , 2022 , 269 ( 10 ): 5382 - 5394 .
van Schependom J , Nagels G . Targeting cognitive impairment in multiple sclerosis-the road toward an imaging-based biomarker [J ] . Front Neurosci , 2017 , 11 : 380 .
Bonnan M , Marasescu R , Demasles S , et al . No evidence of disease activity(NEDA) in MS should include CSF biology-towards a ‘disease-free status score’ [J ] . Mult Scler Relat Disord , 2017 , 11 : 51 - 55 .
Lu G , Beadnall HN , Barton J , et al . The evolution of “no evidence of disease activity” in multiple sclerosis [J ] . Mult Scler Relat Disord , 2018 , 20 : 231 - 238 .
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