Long-Term Safety and Efficacy of Subcutaneous Tanezumab Versus Nonsteroidal Antiinflammatory Drugs for Hip or Knee Osteoarthritis: A Randomized Trial.

OBJECTIVE Assessment of long-term safety and 16-week efficacy of subcutaneous tanezumab in patients with hip or knee OA. METHODS This was a randomized, double-blind, double-dummy, active-controlled (nonsteroidal antiinflammatory drug [NSAID]), phase III safety trial (56-week treatment/24-week post-treatment follow-up) in adults receiving stable dose NSAID therapy at the time of screening and WOMAC1 Pain and Physical Function scores ≥5; patient's global assessment of osteoarthritis (PGA-OA; "fair," "poor," or "very poor"); history of inadequate pain relief with standard analgesics; without history or radiographic evidence of prespecified bone/joint conditions beyond OA. Patients received twice-daily oral naproxen, celecoxib or diclofenac (n=996), versus tanezumab 2.5mg (n=1,002) or 5mg (n=998) every 8-weeks. Primary joint safety endpoint over 80 weeks comprised adjudicated rapidly progressive osteoarthritis type 1 or 2, primary osteonecrosis, subchondral insufficiency fracture, or pathologic fracture. Co-primary efficacy endpoints at week 16 were changes in WOMAC Pain and Physical Function and in PGA-OA scores. RESULTS Of 3,021 randomized patients, 2,996 received ≥1 treatment dose. AEs were similar between tanezumab 2.5mg and NSAID, and more prevalent with tanezumab 5mg. Composite joint safety events were significantly more prevalent with tanezumab 2.5mg and 5mg than NSAID (observation time-adjusted rate/1,000 patient-years [95% CI]) 38.3 [28.0,52.5], P=0.001; 71.5 [56.7,90.2], P<0.001 versus 14.8 [8.9,24.6], respectively. Tanezumab 5mg significantly improved Pain and Physical Function but not PGA-OA at week 16 versus NSAID; corresponding differences for tanezumab 2.5mg were not statistically significant. CONCLUSIONS In patients previously on a stable dose of NSAID, subcutaneous tanezumab resulted in more joint safety events than continued NSAID in a dose-dependent fashion. Pain and physical function improved with tanezumab and NSAID, reaching statistical significance with tanezumab 5mg at 16 weeks.