General Safety and Tolerability of Subcutaneous Tanezumab for Osteoarthritis: A Pooled Analysis of Three Randomized, Placebo-Controlled Trials.

Objective: This pooled analysis of 3 randomized, placebo-controlled trials (16-24 week treatment and 8-24 week follow-up) assessed safety of subcutaneous tanezumab (2.5-10 mg every 8 weeks) in 1,840 patients with hip or knee osteoarthritis.

Methods: 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, and pathologic fracture; adjudicated by an independent expert committee) and TEAEs potentially associated with sympathetic neuropathy were prospectively assessed in 2 trials.

Results: 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 plus 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 paresthesia and hypoesthesia) 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).

Conclusion: 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. A tanezumab dose of 2.5 mg demonstrated a more favorable safety profile than higher doses.