Tanezumab improves pain, function in OA, but safety events higher vs NSAID
Treatment with tanezumab appears to relieve pain and improve physical function in patients with hip or knee osteoarthritis (OA), but may lead to dose-dependent increase in joint safety events as compared with nonsteroidal anti-inflammatory drug (NSAID), according to the results of a phase III safety trial.
The trial involved a 56‐week treatment/24‐week post‐treatment follow‐up of 2,996 adult patients receiving stable dose NSAID therapy. They were randomized to receive twice‐daily oral naproxen, celecoxib, or diclofenac (n=996) or tanezumab at either 2.5 mg (n=1,002) or 5 mg (n=998) every 8 weeks.
At screening, all patients had Western Ontario and McMaster Universities Arthritis Index (WOMAC) 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, and no history or radiographic evidence of prespecified bone/joint conditions beyond OA.
The frequency of adverse events (AEs) was similar with tanezumab 2.5 mg and NSAID but higher with the higher tanezumab dose. Composite joint safety events (adjudicated rapidly progressive osteoarthritis type 1 or 2, primary osteonecrosis, subchondral insufficiency fracture, or pathologic fracture) were significantly more prevalent with both 5- and 10-mg tanezumab doses (observation time‐adjusted rates, 38.3 per 1,000 patient‐years, 95 percent confidence interval [CI], 28.0–52.5 and 71.5 per 1,000 patient‐years, 95 percent CI, 56.7–90.2) than NSAID (observation time‐adjusted rate, 14.8 per 1,000 patient‐years, 95 percent CI, 8.9–24.6; p=0.001 and p<0.001, respectively).
At the higher dose, the study drug significantly improved Pain and Physical Function but not PGA‐OA at week 16 relative to NSAID. The corresponding differences for tanezumab 2.5 mg were not statistically significant.