Efficacy and safety of intravenous tanezumab for the symptomatic treatment of osteoarthritis: 2 randomized controlled trials versus naproxen

J Rheumatol. 2014 Nov;41(11):2249-59. doi: 10.3899/jrheum.131294. Epub 2014 Oct 1.

Abstract

Objective: Two studies evaluated efficacy and safety of tanezumab versus naproxen for treatment of knee or hip osteoarthritis (OA).

Methods: Randomized controlled studies [NCT00830063 (Study 1015, n=828) and NCT00863304 (Study 1018, n=840)] of subjects with hip or knee OA compared intravenous tanezumab (5 mg or 10 mg) to placebo and naproxen (500 mg twice daily). Coprimary outcomes were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain, WOMAC Physical Function (0-10 numerical rating scale), and patient's global assessment of OA at Week 16.

Results: In both studies, tanezumab reduced pain versus placebo [least squares mean differences, 95% CI, tanezumab 5 mg: -1.21 (-1.72, -0.70); -1.13 (-1.65, -0.62); tanezumab 10 mg: -0.91 (-1.42, -0.40); -0.80 (-1.32, -0.29)], and improved function and global scores. Tanezumab 5 mg produced greater pain reduction [-0.76 (-1.28, -0.25); -0.69 (-1.21, -0.17)], and favorable functional and global outcomes versus naproxen. Pain reductions with tanezumab 10 mg versus naproxen did not reach significance, unlike functional (both studies) and global (1 study) outcomes; thus, tanezumab 10 mg was not superior to naproxen, and predefined statistical testing procedures were not met, allowing for conclusion of superiority of tanezumab 5 mg over naproxen despite replicated favorable coprimary outcomes. Tanezumab was associated with greater incidence of peripheral sensory adverse events (paresthesia, hyperesthesia, hypoesthesia, burning sensation), pain in extremity, peripheral edema, and arthralgia. Overall frequency and discontinuations as a result of adverse events were similar to placebo and naproxen.

Conclusion: Tanezumab provides efficacious treatment of knee or hip OA and may have therapeutic utility in patients with OA who experience inadequate analgesia with nonsteroidal antiinflammatory drugs.

Keywords: EFFICACY; NAPROXEN; OSTEOARTHRITIS; SAFETY; TANEZUMAB.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Naproxen / administration & dosage*
  • Naproxen / adverse effects
  • Ontario
  • Osteoarthritis, Hip / diagnosis
  • Osteoarthritis, Hip / drug therapy*
  • Osteoarthritis, Knee / diagnosis
  • Osteoarthritis, Knee / drug therapy*
  • Pain Measurement
  • Patient Safety
  • Range of Motion, Articular / drug effects*
  • Risk Assessment
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Naproxen
  • tanezumab

Associated data

  • ClinicalTrials.gov/NCT00830063
  • ClinicalTrials.gov/NCT00863304