title: Annualized relapse rate of first-line treatments for multiple sclerosis: a meta-analysis, including indirect comparisons versus fingolimod.
abstract: OBJECTIVE
  Previous systematic reviews and meta-analyses of treatments in relapsing-remitting multiple sclerosis (RRMS) derived their findings from either placebo-controlled studies only or separately from head-to-head and comparative studies. The purpose of this study is to compare annualized relapse rates (ARR) of fingolimod versus all of the commonly used first-line treatments in RRMS using evidence from both placebo-controlled and head-to-head studies. In absence of the head-to-head data between fingolimod and the other treatments, these comparisons were formed using meta-analysis techniques for indirect treatment comparisons.
  
  
  METHODS
  A systematic literature review was conducted by searching MEDLINE, EMBASE, and the Cochrane Library with no limitations applied on publication language or dates. Included studies were randomized controlled trials evaluating one or more of fingolimod, interferon beta-1a, interferon beta-1b, or glatiramer acetate in RRMS populations. Primary outcome was ARR. Data extraction included author, year, treatment, dosage, mean age, percentage females, duration of disease, Expanded Disability Status Scale (EDSS) score at baseline, relapses in 2 years prior to baseline, trial duration, relapse-related outcome, and definition of relapse. The indirect treatment comparisons were performed using a mixed-treatment comparison framework. ARR was analyzed as a Poisson outcome.
  
  
  RESULTS
  The relative ARRs, for each treatment versus fingolimod, estimated from our meta-analyses were 1.43 (glatiramer acetate 20 mg), 1.51 (interferon beta-1b 250 mcg), 1.55 (interferon beta-1a 44 mcg), 1.67 (interferon beta-1a 22 mcg), 1.93 (interferon beta-1a 30 mcg), and 2.32 (placebo). None of the 95% confidence intervals for these estimates overlapped unity, implying statistical significance of these findings.
  
  
  CONCLUSIONS
  The key limitations of this study are the persisting heterogeneity even after adjusting for covariates and the variability in outcome definition across the included trials.
  
  
  CONCLUSIONS
  Our study demonstrated that fingolimod significantly reduces relapse frequency in patients with RRMS compared with current first-line disease-modifying therapies.
authors.affiliation: RTI Health Solutions, Manchester, UK. nroskell@rti.org
authors.forename: N S
authors.initials: NS
authors.lastname: Roskell
authors.forename: E A
authors.initials: EA
authors.lastname: Zimovetz
authors.forename: C E
authors.initials: CE
authors.lastname: Rycroft
authors.forename: B J
authors.initials: BJ
authors.lastname: Eckert
authors.forename: D A
authors.initials: DA
authors.lastname: Tyas
mesh_terms: D000328:Adult; D005260:Female; D000068876:Fingolimod Hydrochloride; D000068717:Glatiramer Acetate; D006801:Humans; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D010455:Peptides / Q000627:therapeutic use; D016012:Poisson Distribution; D011409:Propylene Glycols / Q000627:therapeutic use*; D012008:Recurrence; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D010455:Peptides; D011409:Propylene Glycols; D000068576:Interferon beta-1b; D000068717:Glatiramer Acetate; D016899:Interferon-beta; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine; D000068556:Interferon beta-1a