title: Efficacy and safety of tanezumab monotherapy or combined with non-steroidal anti-inflammatory drugs in the treatment of knee or hip osteoarthritis pain.
abstract: OBJECTIVE
  To evaluate whether subjects with knee or hip osteoarthritis (OA) pain on non-steroidal anti-inflammatory drugs (NSAIDs) received greater benefit when tanezumab monotherapy replaced or was coadministered with NSAIDs.
  
  
  METHODS
  Subjects (N=2700) received intravenous tanezumab (5 or 10 mg) or placebo every 8 weeks with or without oral naproxen 500 mg twice daily or celecoxib 100 mg twice daily. Efficacy was assessed as change from baseline to week 16 in three co-primary endpoints: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain, WOMAC Physical Function and Patient's Global Assessment (PGA) of OA. Safety assessments included adverse events, physical and neurological examinations, laboratory tests and vital signs.
  
  
  RESULTS
  Although all tanezumab treatments provided significant improvements in WOMAC Pain and Physical Function over either NSAID alone, only tanezumab+NSAIDs were significant versus NSAIDs with PGA and met the prespecified definition of superiority. Combination treatment did not substantially improve pain or function over tanezumab monotherapy. Adverse event frequency was higher with tanezumab than with NSAIDs and highest with combination therapy. Higher incidence of all-cause total joint replacements occurred with tanezumab+NSAID versus tanezumab monotherapy or NSAIDs. Rapidly progressive OA incidence was significantly greater versus NSAID in all tanezumab groups except tanezumab 5 mg monotherapy.
  
  
  CONCLUSIONS
  Subjects receiving partial symptomatic relief of OA pain with NSAIDs may receive greater benefit with tanezumab monotherapy. While only coadministration of tanezumab with NSAIDs met the definition of superiority, combination treatment did not provide important benefits over tanezumab monotherapy; small differences in efficacy were negated by treatment-limiting or irreversible safety outcomes.
  
  
  BACKGROUND
  NCT00809354.
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Schnitzer
authors.affiliation: Appalachian Regional Orthopaedic & Sports Medicine, Boone, North Carolina, USA.
authors.forename: Evan F
authors.initials: EF
authors.lastname: Ekman
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Egilius L H
authors.initials: EL
authors.lastname: Spierings
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: H Scott
authors.initials: HS
authors.lastname: Greenberg
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Smith
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Brown
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: Christine R
authors.initials: CR
authors.lastname: West
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Verburg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018771:Arthralgia / Q000188:drug therapy* / Q000209:etiology; D019643:Arthroplasty, Replacement / Q000706:statistics & numerical data; D000068579:Celecoxib; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004487:Edema / Q000139:chemically induced; D005260:Female; D006801:Humans; D006987:Hypesthesia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000627:therapeutic use*; D015207:Osteoarthritis, Hip / Q000150:complications / Q000188:drug therapy*; D020370:Osteoarthritis, Knee / Q000150:complications / Q000188:drug therapy*; D010292:Paresthesia / Q000139:chemically induced; D011720:Pyrazoles / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D061067:Antibodies, Monoclonal, Humanized; D011720:Pyrazoles; D013449:Sulfonamides; D009288:Naproxen; C549319:tanezumab; D000068579:Celecoxib