title: New FDA-Approved Disease-Modifying Therapies for Multiple Sclerosis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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 The databases publically available at www.clinicaltrials.gov and www.fda.gov were searched for unpublished studies or studies currently in progress.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Albany College of Pharmacy & Health Sciences, Colchester, Vermont; University of Vermont Medical Center, Burlington, Vermont. Electronic address: clayton.english@acphs.edu.
authors.forename: Clayton
authors.initials: C
authors.lastname: English
authors.affiliation: University of Vermont Medical Center, Burlington, Vermont.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Aloi
mesh_terms: D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000191:economics / Q000627:therapeutic use; D003437:Crotonates / Q000191:economics / Q000627:therapeutic use; D000069462:Dimethyl Fumarate / Q000191:economics / Q000627:therapeutic use; D017277:Drug Approval; D016527:Drug Costs / Q000706:statistics & numerical data; D000068876:Fingolimod Hydrochloride / Q000191:economics / Q000627:therapeutic use; D000068717:Glatiramer Acetate / Q000191:economics / Q000627:therapeutic use; D006801:Humans; D006885:Hydroxybutyrates; D007166:Immunosuppressive Agents / Q000191:economics / Q000627:therapeutic use*; D016899:Interferon-beta / Q000191:economics / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000191:economics; D009570:Nitriles; D011092:Polyethylene Glycols / Q000191:economics / Q000627:therapeutic use; D014052:Toluidines / Q000191:economics / Q000627:therapeutic use; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003437:Crotonates; D006885:Hydroxybutyrates; D007166:Immunosuppressive Agents; D009570:Nitriles; D014052:Toluidines; C527525:teriflunomide; D000074323:Alemtuzumab; D011092:Polyethylene Glycols; D000068717:Glatiramer Acetate; D016899:Interferon-beta; D000069462:Dimethyl Fumarate; D000068876:Fingolimod Hydrochloride; C428112:peginterferon beta-1a
keywords: cost; disease-modifying treatments; multiple sclerosis; new drugs; pharmacotherapy