This pooled analysis of 3 randomized, placebo-controlled trials (16─24 week treatment; 8─24 week follow-up) assessed safety of subcutaneous tanezumab (2.5─10 mg every 8 weeks) in 1840 patients with hip or knee osteoarthritis.
Overall treatment-emergent adverse events (TEAEs) and TEAEs of abnormal peripheral sensation (APS) were prospectively assessed in 3 trials. Joint safety events (primary osteonecrosis, rapidly progressive osteoarthritis [RPOA], subchondral insufficiency fracture, pathological fracture; adjudicated by an independent expert committee) and TEAEs potentially associated with sympathetic neuropathy were prospectively assessed in 2 trials.
During the treatment period, overall TEAE rates were 51.7% for placebo and 39.5─54.8% for tanezumab 2.5─10 mg; treatment discontinuation rates were 2.0% for placebo and 0%-1.3% for tanezumab. Rates of composite joint safety events (predominantly RPOA-type 1) over the treatment + follow-up period were 0% for placebo and 0.5─3.2% for tanezumab 2.5─5 mg (5 mg was statistically greater than placebo); total joint replacement rates with tanezumab (5.9-7.0%) were not significantly different from placebo (4.5%). Rates of TEAEs of APS (predominantly paraesthesia and hypoaesthesia) were 2.2% for placebo and 3.2─12.8% for tanezumab 2.5─10 mg. Rates of TEAEs potentially associated with sympathetic neuropathy (predominantly bradycardia and orthostatic hypotension) were 0.8% for placebo and 0.5─2.8% for tanezumab 2.5─5 mg (exposure-adjusted rates were not significantly different from placebo).
Tanezumab was generally well tolerated. TEAEs of APS (mostly mild and transient) and joint safety events were infrequent but more common with tanezumab than placebo. Tanezumab 2.5 mg demonstrated a more favorable safety profile than higher doses.