title: Comparative efficacy and discontinuation of dimethyl fumarate and fingolimod in clinical practice at 12-month follow-up.
abstract: BACKGROUND
  Dimethyl fumarate (DMF) and fingolimod (FTY) are approved oral disease modifying therapies (DMT) for relapsing multiple sclerosis (MS). Phase 3 trials established these agents as effective and generally well tolerated, though comparative efficacy and discontinuation remain unknown.
  
  
  OBJECTIVE
  To assess real-world efficacy and discontinuation of DMF and FTY over 12 months in patients with MS.
  
  
  METHODS
  We identified 458 DMF-treated and 317 FTY-treated patients in a large academic MS center. Measures of disease activity and discontinuation were compared using propensity score (PS) weighting. Covariates in the PS model included demographics and baseline clinical and MRI characteristics within 12 months of DMT initiation. The primary outcome measure was on-treatment annualized relapse rate (ARR) ratio, which was analyzed using a Poisson regression model. Other measures included time to first relapse, drug discontinuation, time to discontinuation, and new brain MRI lesions at 12 months.
  
  
  RESULTS
  The on-treatment ARR for DMF was 0.16 (95% CI (0.12, 0.18)) and 0.13 (95% CI (0.08, 0.16)) for FTY. PS weighting, which demonstrated excellent covariate balance, showed no differences between groups on ARR (rate ratio=1.56, 95% CI (0.78, 3.14)), overall brain MRI activity defined as new T2 and/or gadolinium enhancing (GdE) lesions (OR=1.38, 95% CI (0.78, 2.42)), new T2 lesions (OR=1.33, 95% CI (0.71, 2.49)), and discontinuation (OR=1.30, 95% CI (0.84, 1.99)). DMF had higher odds of GdE lesions (OR=2.19, 95% CI (1.10, 4.35)), earlier time to discontinuation (HR=1.35, 95% CI (1.05, 1.74)), and earlier relapses (HR=1.64, 95% CI (1.10, 2.46)) compared to FTY.
  
  
  CONCLUSIONS
  Assessment in our clinical practice cohort showed comparable clinical efficacy, overall brain MRI activity, and discontinuation between DMF and FTY at 12 months. DMF had increased GdE lesions and intolerability early after treatment initiation.
authors.affiliation: Lou Ruvo Center for Brain Health, Cleveland Clinic, 888 W. Bonneville Ave, Las Vegas, NV, 89106 USA. Electronic address: hershc@ccf.org.
authors.forename: Carrie M
authors.initials: CM
authors.lastname: Hersh
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, 10900 Euclid Ave, Cleveland, 44106 USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Love
authors.affiliation: Department of Neurology, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, 44195 USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Cohn
authors.affiliation: Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, 44195 USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Hara-Cleaver
authors.affiliation: Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, 44195 USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bermel
authors.affiliation: Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, 44195 USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fox
authors.affiliation: Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, 44195 USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Cohen
authors.affiliation: Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, 44195 USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ontaneda
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects; D000069462:Dimethyl Fumarate / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000000981:diagnostic imaging / Q000188:drug therapy*; D010342:Patient Acceptance of Health Care; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D000069462:Dimethyl Fumarate; D000068876:Fingolimod Hydrochloride
keywords: Comparative efficacy; Dimethyl fumarate; Discontinuation; Fingolimod; Multiple sclerosis