title: Cost-utility analysis of duloxetine in osteoarthritis: a US private payer perspective.
abstract: BACKGROUND
  Duloxetine has recently been approved in the USA for chronic musculoskeletal pain, including osteoarthritis and chronic low back pain. The cost effectiveness of duloxetine in osteoarthritis has not previously been assessed. Duloxetine is targeted as post first-line (after acetaminophen) treatment of moderate to severe pain.
  
  
  OBJECTIVE
  The objective of this study was to estimate the cost effectiveness of duloxetine in the treatment of osteoarthritis from a US private payer perspective compared with other post first-line oral treatments, including nonsteroidal anti-inflammatory drugs (NSAIDs), and both strong and weak opioids.
  
  
  METHODS
  A cost-utility analysis was performed using a discrete-state, time-dependent semi-Markov model based on the National Institute for Health and Clinical Excellence (NICE) model documented in its 2008 osteoarthritis guidelines. The model was extended for opioids by adding titration, discontinuation and additional adverse events (AEs). A life-long time horizon was adopted to capture the full consequences of NSAID-induced AEs. Fourteen health states comprised the structure of the model: treatment without persistent AE, six during-AE states, six post-AE states and death. Treatment-specific utilities were calculated using the transfer-to-utility method and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total scores from a meta-analysis of osteoarthritis clinical trials of 12 weeks and longer. Costs for 2011 were estimated using Red Book, The Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project database, the literature and, sparingly, expert opinion. One-way and probabilistic sensitivity analyses were undertaken, as well as subgroup analyses of patients over 65 years old and a population at greater risk of NSAID-related AEs.
  
  
  RESULTS
  In the base case the model estimated naproxen to be the lowest total-cost treatment, tapentadol the highest cost, and duloxetine the most effective after considering AEs. Duloxetine accumulated 0.027 discounted quality-adjusted life-years (QALYs) more than naproxen and 0.013 more than oxycodone. Celecoxib was dominated by naproxen, tramadol was subject to extended dominance, and strong opioids were dominated by duloxetine. The model estimated an incremental cost-effectiveness ratio (ICER) of US$47,678 per QALY for duloxetine versus naproxen. One-way sensitivity analysis identified the probabilities of NSAID-related cardiovascular AEs as the inputs to which the ICER was most sensitive when duloxetine was compared with an NSAID. When compared with a strong opioid, duloxetine dominated the opioid under nearly all sensitivity analysis scenarios. When compared with tramadol, the ICER was most sensitive to the costs of duloxetine and tramadol. In subgroup analysis, the cost per QALY for duloxetine versus naproxen fell to US$24,125 for patients over 65 years and to US$18,472 for a population at high risk of cardiovascular and gastrointestinal AEs.
  
  
  CONCLUSIONS
  The model estimated that duloxetine was potentially cost effective in the base-case population and more cost effective for subgroups over 65 years or at high risk of NSAID-related AEs. In sensitivity analysis, duloxetine dominated all strong opioids in nearly all scenarios.
authors.affiliation: Medical Decision Modeling Inc., 8909 Purdue Road, Suite #550, Indianapolis, IN 46268, USA. rwielage@mdm-inc.com
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Wielage
authors.forename: Megha
authors.initials: M
authors.lastname: Bansal
authors.forename: J Scott
authors.initials: JS
authors.lastname: Andrews
authors.forename: Robert W
authors.initials: RW
authors.lastname: Klein
authors.forename: Michael
authors.initials: M
authors.lastname: Happich
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000700:Analgesics / Q000191:economics / Q000627:therapeutic use; D000701:Analgesics, Opioid / Q000191:economics / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000191:economics / Q000627:therapeutic use; D059350:Chronic Pain / Q000188:drug therapy; D003362:Cost-Benefit Analysis; D000068736:Duloxetine Hydrochloride; D005260:Female; D006801:Humans; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D018803:Models, Economic; D010003:Osteoarthritis / Q000188:drug therapy* / Q000191:economics*; D011306:Prescription Fees / Q000706:statistics & numerical data; D013876:Thiophenes / Q000191:economics* / Q000627:therapeutic use; D014481:United States
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D013876:Thiophenes; D000068736:Duloxetine Hydrochloride