title: A discrete event simulation to model the cost-utility of fingolimod and natalizumab in rapidly evolving severe relapsing-remitting multiple sclerosis in the UK.
abstract: OBJECTIVE
  Two disease-modifying therapies are licensed in the EU for use in rapidly-evolving severe (RES) relapsing-remitting multiple sclerosis (RRMS), fingolimod and natalizumab. Here a discrete event simulation (DES) model to analyze the cost-effectiveness of natalizumab and fingolimod in the RES population, from the perspective of the National Health Service (NHS) in the UK, is reported.
  
  
  METHODS
  A DES model was developed to track individual RES patients, based on Expanded Disability Status Scale scores. Individual patient characteristics were taken from the RES sub-groups of the pivotal trials for fingolimod. Utility data were in line with previous models. Published costs were inflated to NHS cost year 2015. Owing to the confidential patient access scheme (PAS) discount applied to fingolimod in the UK, a range of discount levels were applied to the fingolimod list price, to capture the likelihood of natalizumab being cost-effective in a real-world setting.
  
  
  RESULTS
  At the lower National Institute of Health and Care Excellence (NICE) threshold of £20,000/quality-adjusted life year (QALY), fingolimod only required a discount greater than 0.8% of list price to be cost-effective. At the upper threshold of £30,000/QALY employed by the NICE, fingolimod was cost-effective if the confidential discount is greater than 2.5%. Sensitivity analyses conducted using fingolimod list-price showed the model to be most sensitive to changes in the cost of each drug, particularly fingolimod.
  
  
  CONCLUSIONS
  The DES model shows that only a modest discount to the UK fingolimod list-price is required to make fingolimod a more cost-effective option than natalizumab in RES RRMS.
authors.affiliation: a Costello Medical Consulting Ltd , Cambridge , UK.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Montgomery
authors.affiliation: a Costello Medical Consulting Ltd , Cambridge , UK.
authors.forename: Maciej J
authors.initials: MJ
authors.lastname: Maruszczak
authors.affiliation: a Costello Medical Consulting Ltd , Cambridge , UK.
authors.forename: David
authors.initials: D
authors.lastname: Slater
authors.affiliation: a Costello Medical Consulting Ltd , Cambridge , UK.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Kusel
authors.affiliation: b Imperial College Healthcare NHS Trust, Charing Cross Hospital , London , UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Nicholas
authors.affiliation: c Novartis Pharmaceuticals UK Ltd , Camberley, Surrey , UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Adlard
mesh_terms: D003198:Computer Simulation; D003362:Cost-Benefit Analysis; D004185:Disability Evaluation; D005252:Fees, Pharmaceutical; D000068876:Fingolimod Hydrochloride / Q000191:economics* / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000191:economics* / Q000627:therapeutic use; D008390:Markov Chains; D017059:Models, Econometric; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000191:economics; D000069442:Natalizumab / Q000191:economics* / Q000627:therapeutic use; D019057:Quality-Adjusted Life Years; D013222:State Medicine; D006113:United Kingdom
chemical_list: D007166:Immunosuppressive Agents; D000069442:Natalizumab; D000068876:Fingolimod Hydrochloride
keywords: Multiple sclerosis; cost-effectiveness; fingolimod; natalizumab; rapidly evolving severe relapsing-remitting multiple sclerosis