title: Cost effectiveness of budesonide/formoterol added to tiotropium bromide versus placebo added to tiotropium bromide in patients with chronic obstructive pulmonary disease: Australian, Canadian and Swedish healthcare perspectives.
abstract: BACKGROUND
  Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory lung disease associated with increasing morbidity and mortality and an economic burden that stretches beyond the patient to healthcare systems. Avoiding exacerbations and subsequent hospitalizations is an important clinical aim and can avoid significant costs associated with the disease. International guidelines recommend the addition of an inhaled corticosteroid (ICS) to a long-acting β₂-adrenoceptor agonist (LABA) for patients with severe to very severe COPD and a history of exacerbations.
  
  
  OBJECTIVE
  To evaluate retrospectively over a 3-month period, the cost effectiveness of budesonide/formoterol added to tiotropium bromide (tiotropium) compared with placebo added to tiotropium in COPD patients eligible for ICS/LABA combination therapy, based on the CLIMB study (NCT00496470).
  
  
  METHODS
  A cost-effectiveness analysis of data from the 12-week, randomized, double-blind CLIMB study of COPD patients (n = 659; eligible for ICS/LABA; aged ≥ 40 years) comparing budesonide/formoterol (Symbicort® Turbuhaler® 320/9 μg twice daily) added to tiotropium (18 μg daily) or placebo added to tiotropium was conducted. A severe exacerbation was defined as a requirement for systemic glucocorticosteroids and/or ED visit and/or hospitalization. The effectiveness variable used for this analysis was the number of severe exacerbations avoided. Direct costs (medications, hospitalizations, ED and GP visits) were calculated by applying year 2009 unit costs from Australia ($A), Canada ($Can) and Sweden (Swedish krona [SEK]) to the study's pooled resource use. One-way sensitivity analyses for each country's mean incremental cost-effectiveness ratio and sensitivity to overall exacerbations were conducted. Bootstrapping was performed to estimate the variation around resource use, exacerbations and each country's mean incremental cost-effectiveness ratio.
  
  
  RESULTS
  The mean number of severe exacerbations per patient 3-month period was 0.11 in the budesonide/formoterol added to tiotropium arm and 0.29 in the placebo added to tiotropium arm--a 62% reduction in the rate of severe exacerbations. Treatment with budesonide/formoterol added to tiotropium costs less in Australia and Canada (-$A90 [-€58] and -$Can4.51 [-€3]) and only slightly more in Sweden (SEK444 [€43]), i.e. the savings associated with fewer exacerbations more than offset the additional budesonide/formoterol drug cost in Australia and Canada, and partially offset it in Sweden. In the Australian and Canadian perspectives, budesonide/formoterol added to tiotropium was a dominant treatment (fewer exacerbations at a lower cost) compared with placebo added to tiotropium. In Sweden, the estimated incremental cost per avoided exacerbation was SEK2502 (€244.40).
  
  
  CONCLUSIONS
  Budesonide/formoterol added to tiotropium was the dominant strategy compared with placebo added to tiotropium based on a 12-week study in COPD patients eligible for ICS/LABA combination therapy in Australia and Canada, and appears to be a cost-effective strategy in Sweden.
authors.affiliation: Health Outcomes and PharmacoEconomic (HOPE) Research Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. nicole.mittmann@sunnybrook.ca
authors.forename: Nicole
authors.initials: N
authors.lastname: Mittmann
authors.forename: Paul
authors.initials: P
authors.lastname: Hernandez
authors.forename: Carl
authors.initials: C
authors.lastname: Mellström
authors.forename: Lance
authors.initials: L
authors.lastname: Brannman
authors.forename: Tobias
authors.initials: T
authors.lastname: Welte
mesh_terms: D001315:Australia; D019819:Budesonide / Q000008:administration & dosage / Q000191:economics* / Q000627:therapeutic use; D002170:Canada; D003362:Cost-Benefit Analysis; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000008:administration & dosage / Q000191:economics* / Q000627:therapeutic use; D000068759:Formoterol Fumarate; D017048:Health Care Costs / Q000639:trends; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000191:economics*; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D012602:Scopolamine Derivatives / Q000008:administration & dosage / Q000191:economics* / Q000627:therapeutic use; D013548:Sweden; D000069447:Tiotropium Bromide
chemical_list: D004983:Ethanolamines; D012602:Scopolamine Derivatives; D019819:Budesonide; D000068759:Formoterol Fumarate; D000069447:Tiotropium Bromide