title: Cost-effectiveness of nonsteroidal anti-inflammatory drugs and opioids in the treatment of knee osteoarthritis in older patients with multiple comorbidities.
abstract: OBJECTIVE
  To evaluate long-term clinical and economic outcomes of naproxen, ibuprofen, celecoxib or tramadol for OA patients with cardiovascular disease (CVD) and diabetes.
  
  
  METHODS
  We used the Osteoarthritis Policy Model to examine treatment with these analgesics after standard of care (SOC) - acetaminophen and corticosteroid injections - failed to control pain. NSAID regimens were evaluated with and without proton pump inhibitors (PPIs). We evaluated over-the-counter (OTC) regimens where available. Estimates of treatment efficacy (pain reduction, occurring in ∼57% of patients on all regimens) and toxicity (major cardiac or gastrointestinal toxicity or fractures, risk ranging from 1.09% with celecoxib to 5.62% with tramadol) were derived from published literature. Annual costs came from Red Book Online(®). Outcomes were discounted at 3%/year and included costs, quality-adjusted life expectancy, and incremental cost-effectiveness ratios (ICERs). Key input parameters were varied in sensitivity analyses.
  
  
  RESULTS
  Adding ibuprofen to SOC was cost saving, increasing QALYs by 0.07 while decreasing cost by $800. Incorporating OTC naproxen rather than ibuprofen added 0.01 QALYs and increased costs by $300, resulting in an ICER of $54,800/QALY. Using prescription naproxen with OTC PPIs led to an ICER of $76,700/QALY, while use of prescription naproxen with prescription PPIs resulted in an ICER of $252,300/QALY. Regimens including tramadol or celecoxib cost more but added fewer QALYs and thus were dominated by several of the naproxen-containing regimens.
  
  
  CONCLUSIONS
  In patients with multiple comorbidities, naproxen- and ibuprofen-containing regimens are more effective and cost-effective in managing OA pain than opioids, celecoxib or SOC.
authors.affiliation: Orthopaedic and Arthritis Center for Outcomes Research (OrACORe), Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, MA, USA; Division of Rheumatology, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: jnkatz@partners.org.
authors.forename: J N
authors.initials: JN
authors.lastname: Katz
authors.affiliation: Orthopaedic and Arthritis Center for Outcomes Research (OrACORe), Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, MA, USA. Electronic address: ssmith94@partners.org.
authors.forename: S R
authors.initials: SR
authors.lastname: Smith
authors.affiliation: Orthopaedic and Arthritis Center for Outcomes Research (OrACORe), Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: jcollins13@partners.org.
authors.forename: J E
authors.initials: JE
authors.lastname: Collins
authors.affiliation: Division of Rheumatology, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: dsolomon@partners.org.
authors.forename: D H
authors.initials: DH
authors.lastname: Solomon
authors.affiliation: The Division of Rheumatology, Allergy and Immunology, Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, NC, USA. Electronic address: joanne_jordan@med.unc.edu.
authors.forename: J M
authors.initials: JM
authors.lastname: Jordan
authors.affiliation: Institute of Bone and Joint Research, Kolling Institute, University of Sydney, Sydney, Australia; Rheumatology Department, Royal North Shore Hospital, Sydney, Australia. Electronic address: david.hunter@sydney.edu.au.
authors.forename: D J
authors.initials: DJ
authors.lastname: Hunter
authors.affiliation: Yale School of Medicine, New Haven, CT, USA; Veterans Affairs Medical Center, West Haven, CT, USA. Electronic address: lisa.suter@yale.edu.
authors.forename: L G
authors.initials: LG
authors.lastname: Suter
authors.affiliation: University of California, San Francisco, San Francisco, CA, USA. Electronic address: ed.yelin@ucsf.edu.
authors.forename: E
authors.initials: E
authors.lastname: Yelin
authors.affiliation: Yale School of Medicine, New Haven, CT, USA; Yale School of Public Health, New Haven, CT, USA. Electronic address: david.paltiel@yale.edu.
authors.forename: A D
authors.initials: AD
authors.lastname: Paltiel
authors.affiliation: Orthopaedic and Arthritis Center for Outcomes Research (OrACORe), Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: elosina@partners.org.
authors.forename: E
authors.initials: E
authors.lastname: Losina
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D000068579:Celecoxib / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use; D015897:Comorbidity; D003362:Cost-Benefit Analysis; D016527:Drug Costs / Q000706:statistics & numerical data; D004359:Drug Therapy, Combination / Q000191:economics; D005260:Female; D006302:Health Services Research / Q000379:methods; D006801:Humans; D007052:Ibuprofen / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use; D004366:Nonprescription Drugs / Q000191:economics / Q000627:therapeutic use; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000191:economics*; D010146:Pain / Q000188:drug therapy / Q000191:economics; D010147:Pain Measurement / Q000379:methods; D054328:Proton Pump Inhibitors / Q000191:economics / Q000627:therapeutic use; D019057:Quality-Adjusted Life Years; D012680:Sensitivity and Specificity; D014147:Tramadol / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use; D016896:Treatment Outcome; D014481:United States
chemical_list: D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004366:Nonprescription Drugs; D054328:Proton Pump Inhibitors; D014147:Tramadol; D009288:Naproxen; D000068579:Celecoxib; D007052:Ibuprofen
keywords: Cost-effectiveness; NSAIDS; Nonsteroidal anti-inflammatory drugs; Opioids; Osteoarthritis