English Clayton, Aloi Joseph J
Albany College of Pharmacy & Health Sciences, Colchester, Vermont; University of Vermont Medical Center, Burlington, Vermont.
University of Vermont Medical Center, Burlington, Vermont.
Clin Ther. 2015 Apr 1;37(4):691-715. doi: 10.1016/j.clinthera.2015.03.001. Epub 2015 Apr 4.
Interferon injectables and glatiramer acetate have served as the primary disease-modifying treatments for multiple sclerosis (MS) since their introduction in the 1990s and are first-line treatments for relapsing-remitting forms of MS (RRMS). Many new drug therapies were launched since early 2010, expanding the drug treatment options considerably in a disease state that once had a limited treatment portfolio. The purpose of this review is to critically evaluate the safety profile and efficacy data of disease-modifying agents for MS approved by the US Food and Drug Administration (FDA) from 2010 to the present and provide cost and available pharmacoeconomic data about each new treatment.
Peer-reviewed clinical trials, pharmacoeconomic studies, and relevant pharmacokinetic/pharmacologic studies were identified from MEDLINE (January 2000-December 2014) by using the search terms multiple sclerosis, fingolimod, teriflunomide, alemtuzumab, dimethyl fumarate, pegylated interferon, peginterferon beta-1a, glatiramer 3 times weekly, and pharmacoeconomics. Citations from available articles were also reviewed for additional references. The databases publically available at www.clinicaltrials.gov and www.fda.gov were searched for unpublished studies or studies currently in progress.
A total of 5 new agents and 1 new dosage formulation were approved by the FDA for the treatment of RRMS since 2010. Peginterferon beta-1a and high-dose glatiramer acetate represent 2 new effective injectable options for MS that reduce burden of administration seen with traditional interferon and low-dose glatiramer acetate. Fingolimod, teriflunomide, and dimethyl fumarate represent new oral agents available for MS, and their efficacy in reducing annualized relapse rates is 48% to 55%, 22% to 36.3%, and 44% to 53%, respectively, compared with placebo. Alemtuzumab is a biologic given over a 2-year span that reduced annualized relapse rates by 55% in treatment-naive patients and by 49% in patients relapsing on prior disease-modifying agents. Treatment emergent adverse effects were common with all new drug treatments. The cost of treating MS remains high, because MS therapies accounted for the highest spending growth of any specialty drug class in 2013. Most therapies cost, on average, US $6000/mo based on wholesale acquisition cost, and few cost-benefit studies are available for new treatments.
With expansion of new treatments, patients and providers now have multiple options and improved flexibility in managing MS. The relative place in therapy of new treatments is unknown, and treatment decisions are largely based on patient preference, efficacy, and risk potential. The cost of treating MS continues to be high, even with more treatment options available.
自20世纪90年代干扰素注射剂和醋酸格拉替雷上市以来，它们一直是治疗多发性硬化症（MS）的主要疾病改善疗法，也是复发缓解型MS（RRMS）的一线治疗方法。自2010年初以来，许多新的药物疗法相继推出，在这个曾经治疗方案有限的疾病领域极大地扩展了药物治疗选择。本综述的目的是严格评估2010年至今美国食品药品监督管理局（FDA）批准的用于MS的疾病改善药物的安全性和疗效数据，并提供每种新疗法的成本及可用的药物经济学数据。
通过使用搜索词“多发性硬化症”“芬戈莫德”“特立氟胺”“阿仑单抗”“富马酸二甲酯”“聚乙二醇化干扰素”“聚乙二醇化干扰素β-1a”“每周3次的醋酸格拉替雷”和“药物经济学”，从MEDLINE（2000年1月至2014年12月）中检索经过同行评审的临床试验、药物经济学研究以及相关的药代动力学/药理学研究。还对现有文章的参考文献进行了查阅以获取更多参考资料。在www.clinicaltrials.gov和www.fda.gov上公开的数据库中搜索未发表的研究或正在进行的研究。
自2010年以来，FDA共批准了5种新药物和1种新剂型用于治疗RRMS。聚乙二醇化干扰素β-1a和高剂量醋酸格拉替雷是MS的两种新的有效注射选择，它们减轻了传统干扰素和低剂量醋酸格拉替雷带来的给药负担。芬戈莫德、特立氟胺和富马酸二甲酯是MS可用的新型口服药物与安慰剂相比，它们降低年化复发率的疗效分别为48%至55%、22%至36.3%和44%至53%。阿仑单抗是一种在2年时间内给药的生物制剂，在未接受过治疗的患者中，其年化复发率降低了55%，在先前使用疾病改善药物后复发的患者中降低了49%。所有新药物治疗中治疗后出现的不良反应都很常见。治疗MS的成本仍然很高，因为MS治疗在2013年是所有专科药物类别中支出增长最高的。基于批发采购成本，大多数疗法平均每月花费6000美元，而且针对新疗法的成本效益研究很少。
随着新治疗方法的扩展，患者和医疗服务提供者在管理MS方面现在有了多种选择和更高的灵活性。新疗法在治疗中的相对地位尚不清楚，治疗决策很大程度上基于患者的偏好、疗效和潜在风险。即使有更多的治疗选择，治疗MS的成本仍然很高。
