title: Cost-effectiveness of adalimumab, etanercept, and tocilizumab as first-line treatments for moderate-to-severe rheumatoid arthritis.
abstract: OBJECTIVE
  The aim of this study was to assess the cost-utility and value of reducing the uncertainty associated with the decision to use first-line biologic treatment (bDMARD) after the failure of one or more traditional drugs (tDMARD) in moderate-to-severe rheumatoid arthritis (msRA) in Finland.
  
  
  METHODS
  The treatment sequences were compared among 3000 hypothetical Finnish msRA patients using a probabilistic microsimulation model in a lifetime scenario. Adalimumab + methotrexate, etanercept + methotrexate, or tocilizumab + methotrexate were used as first biologics followed by rituximab + methotrexate and infliximab + methotrexate. Best supportive care (BSC), including tDMARDs, was assumed to be used after the exhaustion of the biologics. Methotrexate alone was added as a further comparator. Efficacy was based on ACR responses that were obtained from a mixed treatment comparison. The resources were valued with Finnish unit costs (year 2010) from the healthcare payer perspective. Additional analyses were carried out, including productivity losses. The Health Assessment Questionnaire (HAQ) values were mapped to the EQ-5D values using the tocilizumab trials; 3% annual discounting for costs and quality-adjusted life years (QALY) and extensive sensitivity analyses were completed.
  
  
  METHODS
  Incremental cost per QALY gained and multinomial expected value of perfect information (mEVPI).
  
  
  RESULTS
  bDMARDs significantly increase the QALYs gained when compared to methotrexate alone. Tocilizumab + methotrexate was more cost-effective than adalimumab + methotrexate or etanercept + methotrexate in comparison with methotrexate alone, and adalimumab + methotrexate was dominated by etanercept + methotraxate. A QALY gained with retail-priced (wholesale-priced) tocilizumab + methotrexate costs €18,957 (€17,057) compared to methotrexate alone. According to the cost-effectiveness efficiency frontier and cost-effectiveness acceptability frontier (CEAF), tocilizumab + methotrexate should be considered before rituximab + methotrexate, infliximab + methotrexate, and BSC. Based on the CEAF, tocilizumab + methotrexate had a 60-93% probability of being cost-effective with €20,000 per QALY gained (mEVPI €230-2182).
  
  
  CONCLUSIONS
  Tocilizumab + methotrexate is a potentially cost-effective bDMARD treatment for msRA, indicating a low value of additional research information with the international threshold values.
  
  
  CONCLUSIONS
  Efficacy based on an indirect comparison (certolizumab pegol, golimumab excluded), fixed treatment sequence after the exhaustion of first bDMARD, Swedish resource use data according to HAQ scores, and inpatient costs assumed to include surgery.
authors.affiliation: ESiOR Oy, Kuopio, Finland. erkki.soini@esior.fi
authors.forename: E J
authors.initials: EJ
authors.lastname: Soini
authors.forename: T A
authors.initials: TA
authors.lastname: Hallinen
authors.forename: K
authors.initials: K
authors.lastname: Puolakka
authors.forename: V
authors.initials: V
authors.lastname: Vihervaara
authors.forename: M J
authors.initials: MJ
authors.lastname: Kauppi
mesh_terms: D000068879:Adalimumab; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000191:economics* / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000191:economics* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology*; D003362:Cost-Benefit Analysis / Q000379:methods; D057915:Drug Substitution / Q000191:economics; D000068800:Etanercept; D005260:Female; D005387:Finland / Q000453:epidemiology; D006295:Health Resources / Q000706:statistics & numerical data; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000191:economics* / Q000627:therapeutic use; D008297:Male; D017063:Outcome Assessment, Health Care; D011788:Quality of Life; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage / Q000627:therapeutic use; D012720:Severity of Illness Index; D017211:Treatment Failure
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000068879:Adalimumab; C502936:tocilizumab; D000068800:Etanercept