title: Oral disease-modifying therapies for relapsing-remitting multiple sclerosis.
abstract: OBJECTIVE
  The efficacy and safety of the three oral agents approved by the Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis (RRMS) are reviewed.
  
  
  CONCLUSIONS
  Limitations to parenteral disease-modifying therapies (DMTs) (interferon beta-1a, interferon beta-1b, and glatiramer acetate) for the treatment of RRMS have been addressed by the approval of three oral DMTs: fingolimod, teriflunomide, and dimethyl fumarate. In clinical trials, each of the oral DMTs was superior to placebo in annualized relapse rate, a key indicator of clinical efficacy, and in neuroradiological efficacy. A reduction in disability progression was evident with higher doses of teriflunomide but was not consistently demonstrated with fingolimod or dimethyl fumarate. Each of the oral DMTs demonstrated acceptable safety in clinical trials, with adverse-effect profiles that differ from injectable agents. The safety of both teriflunomide and dimethyl fumarate is supported by long-term use of related agents for other diseases; however, postmarketing surveillance studies are needed to determine the safety of each of the oral DMTs in patients with RRMS. Dimethyl fumarate seems to have the most innocuous safety profile of the three agents. Fingolimod requires first-dose inpatient monitoring due to cardiac safety concerns and multiple laboratory tests prior to initiation of therapy, while teriflunomide has been associated with hepatotoxicity and teratogenicity.
  
  
  CONCLUSIONS
  With the approval of three oral drugs for RRMS-fingolimod, teriflunomide, and dimethyl fumarate-the therapeutic strategy for RRMS has evolved to include options that are efficacious and appear to have administration advantages over established parenteral treatments.
authors.affiliation: Rachel Hutchins Thomas, Pharm.D., M.S., is Clinical Pharmacist, Shelby Baptist Medical Center, Alabaster, AL; at the time of writing she was Assistant Professor of Pharmacy Practice, McWhorter School of Pharmacy, Sanford University, Birmingham, AL. Richard A. Wakefield, Pharm.D., is Clinical Pharmacist, St. Dominic-Jackson Memorial Hospital, Jackson, MS; at the time of writing he was Resident, Drug Information Practice, McWhorter School of Pharmacy, Samford University. rahutchi@samford.edu.
authors.forename: Rachel Hutchins
authors.initials: RH
authors.lastname: Thomas
authors.affiliation: Rachel Hutchins Thomas, Pharm.D., M.S., is Clinical Pharmacist, Shelby Baptist Medical Center, Alabaster, AL; at the time of writing she was Assistant Professor of Pharmacy Practice, McWhorter School of Pharmacy, Sanford University, Birmingham, AL. Richard A. Wakefield, Pharm.D., is Clinical Pharmacist, St. Dominic-Jackson Memorial Hospital, Jackson, MS; at the time of writing he was Resident, Drug Information Practice, McWhorter School of Pharmacy, Samford University.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Wakefield
mesh_terms: D000284:Administration, Oral; D003437:Crotonates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000069462:Dimethyl Fumarate; D018450:Disease Progression; D017277:Drug Approval; D000068876:Fingolimod Hydrochloride; D005650:Fumarates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D006885:Hydroxybutyrates; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000503:physiopathology; D009570:Nitriles; D011409:Propylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D013110:Sphingosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D014052:Toluidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D003437:Crotonates; D005650:Fumarates; D006885:Hydroxybutyrates; D007166:Immunosuppressive Agents; D009570:Nitriles; D011409:Propylene Glycols; D014052:Toluidines; C527525:teriflunomide; D000069462:Dimethyl Fumarate; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine