title: Cost effectiveness of adding leflunomide to a 5-year strategy of conventional disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  To estimate, from a public payer's perspective, the 5-year cost effectiveness of adding leflunomide (LEF) to a sequence of disease-modifying antirheumatic drugs (DMARDs) representative of a typical rheumatoid arthritis (RA) management approach adopted by Canadian rheumatologists.
  
  
  METHODS
  A DMARD sequence including LEF was compared with one excluding it, using a 5-year simulation model where patients with RA cycle through different treatment regimens. Data were obtained through a systematic literature search (drug withdrawal rates, number and type of adverse events, American College of Rheumatology 20% responder status) and separately conducted surveys (choice of DMARD sequence, management of adverse events). Costs for adverse event management were calculated using the Ontario Schedule of Benefits, and monitoring costs were calculated according to official Canadian product monograph recommendations. Wholesale prices of all drugs were adjusted by the allowable markup and prescription fees. Utilities (as measured by the standard gamble [SG] and rating scale [RS] techniques) were obtained from 482 patients who participated in a 1-year randomized controlled trial that compared LEF, methotrexate, and placebo. Costs and utilities were discounted by 3%. Probabilistic sensitivity analysis was performed.
  
  
  RESULTS
  Adding LEF to a conventional strategy of DMARDs increased the 5-year management costs by $1,231 compared with the strategy without LEF, which results in a cost-effectiveness ratio of $13,096 per additional year of response to treatment, and cost-utility ratios of $54,229 (RS) and $71,988 (SG) per quality-adjusted life-year gained.
  
  
  CONCLUSIONS
  Adding LEF as a new option to a conventional sequence of DMARDs extends the time patients may benefit from DMARD therapy at a reasonable cost effectiveness and cost utility. LEF data are limited to clinical trials; data from observational studies would be needed to corroborate these findings.
authors.affiliation: University Health Network Research Institute, Toronto, Ontario, Canada. maetzel@uhnres.utoronto.ca
authors.forename: Andreas
authors.initials: A
authors.lastname: Maetzel
authors.forename: Vibeke
authors.initials: V
authors.lastname: Strand
authors.forename: Peter
authors.initials: P
authors.lastname: Tugwell
authors.forename: George
authors.initials: G
authors.lastname: Wells
authors.forename: Claire
authors.initials: C
authors.lastname: Bombardier
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000191:economics / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000191:economics / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000191:economics*; D002170:Canada; D003362:Cost-Benefit Analysis; D003663:Decision Trees; D004359:Drug Therapy, Combination; D017850:Economics, Pharmaceutical; D017048:Health Care Costs; D006801:Humans; D007555:Isoxazoles / Q000191:economics / Q000627:therapeutic use*; D000077339:Leflunomide; D015233:Models, Statistical; D011336:Probability
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D007555:Isoxazoles; D000077339:Leflunomide