title: Efficacy and safety of BG-12 (dimethyl fumarate) and other disease-modifying therapies for the treatment of relapsing-remitting multiple sclerosis: a systematic review and mixed treatment comparison.
abstract: OBJECTIVE
  Currently, direct comparative evidence or head-to-head data between BG-12 (dimethyl fumarate) and other disease-modifying treatments (DMTs) is limited. This study is a systematic review and data synthesis of published randomized clinical trials comparing the efficacy and safety of existing DMTs to BG-12 for relapsing-remitting multiple sclerosis (RRMS).
  
  
  METHODS
  A systematic review was conducted by searching MEDLINE, EMBASE, and the Cochrane Library for English-language publications from 1 January 1960 to 15 November 2012. Clinicaltrials.gov, metaRegister of Controlled Trials, and conference proceedings from relevant annual symposia were also hand searched. Two independent reviewers collected and extracted data, with discrepancies reconciled by a third reviewer. Included studies were randomized controlled trials (RCTs) of DMTs (interferon [IFN] beta-1a, IFN beta-1b, glatiramer acetate [GA], BG-12, fingolimod, natalizumab, and teriflunomide) in adults with RRMS. Mixed treatment comparisons were conducted to derive the relative effect size for the included treatments. Annualized relapse rate (ARR), disability progression, and safety outcomes were assessed.
  
  
  RESULTS
  BG-12 240 mg twice a day (BID) significantly reduces ARR compared to placebo (rate ratio: 0.529 [95% CI: 0.451-0.620]), IFNs (0.76 [95% CI: 0.639-0.904]), GA (0.795 [95% CI: 0.668-0.947]), and teriflunomide 7 mg and 14 mg (0.769 [95% CI: 0.610-0.970] and 0.775 [95% CI: 0.614-0.979]), and does not show a significant difference when compared to fingolimod. Only natalizumab was significantly superior to BG-12 in reducing ARR. BG-12 also demonstrated favorable results for disability and safety outcomes.
  
  
  CONCLUSIONS
  Based on indirect comparison, BG-12 offers an effective oral treatment option for patients with RRMS with an overall promising efficacy and safety profile compared to currently approved DMTs. Key limitations of the systematic review were the large heterogeneity in patients enrolled and the variability in the definition of outcomes in included trials.
authors.affiliation: Newman Clinical Research Professor, St Vincent's University Hospital, University College Dublin , Ireland.
authors.forename: Michael
authors.initials: M
authors.lastname: Hutchinson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fox
authors.forename: Eva
authors.initials: E
authors.lastname: Havrdova
authors.forename: Nuwan C
authors.initials: NC
authors.lastname: Kurukulasuriya
authors.forename: Sujata P
authors.initials: SP
authors.lastname: Sarda
authors.forename: Sonalee
authors.initials: S
authors.lastname: Agarwal
authors.forename: Mohd Kashif
authors.initials: MK
authors.lastname: Siddiqui
authors.forename: Ankush
authors.initials: A
authors.lastname: Taneja
authors.forename: Baris
authors.initials: B
authors.lastname: Deniz
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D003437:Crotonates / Q000627:therapeutic use; D000069462:Dimethyl Fumarate; D018450:Disease Progression; D000068876:Fingolimod Hydrochloride; D005650:Fumarates / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006885:Hydroxybutyrates; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000627:therapeutic use; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D000069442:Natalizumab; D009570:Nitriles; D011409:Propylene Glycols / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D013110:Sphingosine / Q000031:analogs & derivatives / Q000627:therapeutic use; D014052:Toluidines / Q000627:therapeutic use
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003437:Crotonates; D005650:Fumarates; D006885:Hydroxybutyrates; D000069442:Natalizumab; D009570:Nitriles; D011409:Propylene Glycols; D014052:Toluidines; D000068576:Interferon beta-1b; C527525:teriflunomide; D016899:Interferon-beta; D000069462:Dimethyl Fumarate; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine; D000068556:Interferon beta-1a