title: Model-based evaluation of cost-effectiveness of nerve growth factor inhibitors in knee osteoarthritis: impact of drug cost, toxicity, and means of administration.
abstract: OBJECTIVE
  Studies suggest nerve growth factor inhibitors (NGFi) relieve pain but may accelerate disease progression in some patients with osteoarthritis (OA). We sought cost and toxicity thresholds that would make NGFi a cost-effective treatment for moderate-to-severe knee OA.
  
  
  METHODS
  We used the Osteoarthritis Policy (OAPol) model to estimate the cost-effectiveness of NGFi compared to standard of care (SOC) in OA, using Tanezumab as an example. Efficacy and rates of accelerated OA progression were based on published studies. We varied the price/dose from $200 to $1000. We considered self-administered subcutaneous (SC) injections (no administration cost) vs provider-administered intravenous (IV) infusion ($69-$433/dose). Strategies were defined as cost-effective if their incremental cost-effectiveness ratio (ICER) was less than $100,000/quality-adjusted life year (QALY). In sensitivity analyses we varied efficacy, toxicity, and costs.
  
  
  RESULTS
  SOC in patients with high levels of pain led to an average discounted quality-adjusted life expectancy of 11.15 QALYs, a lifetime risk of total knee replacement surgery (TKR) of 74%, and cumulative discounted direct medical costs of $148,700. Adding Tanezumab increased QALYs to 11.42, reduced primary TKR utilization to 63%, and increased costs to between $155,400 and $199,500. In the base-case analysis, Tanezumab at $600/dose was cost-effective when delivered outside of a hospital. At $1000/dose, Tanezumab was not cost-effective in all but the most optimistic scenario. Only at rates of accelerated OA progression of 10% or more (10-fold higher than reported values) did Tanezumab decrease QALYs and fail to represent a viable option.
  
  
  CONCLUSIONS
  At $100,000/QALY, Tanezumab would be cost effective if priced ≤$400/dose in all settings except IV hospital delivery.
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
authors.affiliation: Orthopaedic and Arthritis Center for Outcomes Research (OrACORe), Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, MA, USA. Electronic address: griffinmichl@gmail.com.
authors.forename: G
authors.initials: G
authors.lastname: Michl
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: Institute of Bone and Joint Research, Kolling Institute, University of Sydney, and 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: Thurston Arthritis Research Center and the Division of Rheumatology, Allergy and Immunology, University of North Carolina, Chapel Hill, USA. Electronic address: joanne_jordan@med.unc.edu.
authors.forename: J M
authors.initials: JM
authors.lastname: Jordan
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 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; Orthopaedic and Arthritis Center for Outcomes Research (OrACORe), 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
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000191:economics* / Q000627:therapeutic use; D003362:Cost-Benefit Analysis; D018450:Disease Progression; D016527:Drug Costs / Q000706:statistics & numerical data*; D005260:Female; D017048:Health Care Costs; D006302:Health Services Research / Q000379:methods; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D017059:Models, Econometric; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors*; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000191:economics; D010147:Pain Measurement / Q000379:methods; D019057:Quality-Adjusted Life Years; D012646:Self Administration / Q000191:economics; D014481:United States
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D061067:Antibodies, Monoclonal, Humanized; C502240:NGF protein, human; D020932:Nerve Growth Factor; C549319:tanezumab
keywords: Cost-effectiveness; Nerve growth factor inhibitors; Osteoarthritis; Tanezumab