title: Cost-utility of First-line Disease-modifying Treatments for Relapsing-Remitting Multiple Sclerosis.
abstract: OBJECTIVE
  This study evaluated the cost-effectiveness of first-line treatments of relapsing-remitting multiple sclerosis (RRMS) (dimethyl fumarate [DMF] 240 mg PO BID, teriflunomide 14 mg once daily, glatiramer acetate 20 mg SC once daily, interferon [IFN]-β1a 44 µg TIW, IFN-β1b 250 µg EOD, and IFN-β1a 30 µg IM QW) and best supportive care (BSC) in the health care payer setting in Finland.
  
  
  METHODS
  The primary outcome was the modeled incremental cost-effectiveness ratio (ICER; €/quality-adjusted life-year [QALY] gained, 3%/y discounting). Markov cohort modeling with a 15-year time horizon was employed. During each 1-year modeling cycle, patients either maintained the Expanded Disability Status Scale (EDSS) score or experienced progression, developed secondary progressive MS (SPMS) or showed EDSS progression in SPMS, experienced relapse with/without hospitalization, experienced an adverse event (AE), or died. Patients׳ characteristics, RRMS progression probabilities, and standardized mortality ratios were derived from a registry of patients with MS in Finland. A mixed-treatment comparison (MTC) informed the treatment effects. Finnish EuroQol Five-Dimensional Questionnaire, Three-Level Version quality-of-life and direct-cost estimates associated with EDSS scores, relapses, and AEs were applied. Four approaches were used to assess the outcomes: cost-effectiveness plane and efficiency frontiers (relative value of efficient treatments); cost-effectiveness acceptability frontier, which demonstrated optimal treatment to maximize net benefit; Bayesian treatment ranking (BTR); and an impact investment assessment (IIA; a cost-benefit assessment), which increased the clinical interpretation and appeal of modeled outcomes in terms of absolute benefit gained with fixed drug-related budget. Robustness of results was tested extensively with sensitivity analyses.
  
  
  RESULTS
  Based on the modeled results, teriflunomide was less costly, with greater QALYs, versus glatiramer acetate and the IFNs. Teriflunomide had the lowest ICER (24,081) versus BSC. DMF brought marginally more QALYs (0.089) than did teriflunomide, with greater costs over the 15 years. The ICER for DMF versus teriflunomide was 75,431. Teriflunomide had >50% cost-effectiveness probabilities with a willingness-to-pay threshold of <€77,416/QALY gained. According to BTR, teriflunomide was first-best among the disease-modifying therapies, with potential willingness-to-pay thresholds of up to €68,000/QALY gained. In the IIA, teriflunomide was associated with the longest incremental quality-adjusted survival and time without cane use. Generally, primary outcomes results were robust, based on the sensitivity analyses. The results were sensitive only to large changes in analysis perspective or mixed-treatment comparison.
  
  
  CONCLUSIONS
  The results were sensitive only to large changes in analysis perspective or MTC. Based on the analyses, teriflunomide was cost-effective versus BSC or DMF with the common threshold values, was dominant versus other first-line RRMS treatments, and provided the greatest impact on investment. Teriflunomide is potentially the most cost-effective option among first-line treatments of RRMS in Finland.
authors.affiliation: ESiOR Oy, Kuopio, Finland. Electronic address: erkki.soini@esior.fi.
authors.forename: Erkki
authors.initials: E
authors.lastname: Soini
authors.affiliation: Genzyme (a Sanofi Company), Helsinki, Finland.
authors.forename: Jaana
authors.initials: J
authors.lastname: Joutseno
authors.affiliation: School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Marja-Liisa
authors.initials: ML
authors.lastname: Sumelahti
mesh_terms: D000328:Adult; D001499:Bayes Theorem; D003362:Cost-Benefit Analysis; D003437:Crotonates / Q000627:therapeutic use*; D000069462:Dimethyl Fumarate / Q000627:therapeutic use*; D005260:Female; D000068717:Glatiramer Acetate / Q000627:therapeutic use*; D006801:Humans; D006885:Hydroxybutyrates; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D009570:Nitriles; D019057:Quality-Adjusted Life Years; D014052:Toluidines / Q000627:therapeutic use*
chemical_list: D003437:Crotonates; D006885:Hydroxybutyrates; D009570:Nitriles; D014052:Toluidines; C527525:teriflunomide; D000068717:Glatiramer Acetate; D000069462:Dimethyl Fumarate
keywords: cost-effectiveness; dimethyl fumarate; economic evaluation; glatiramer acetate; interferon-β; teriflunomide