Efficacy and safety of intravenous tanezumab in osteoarthritis hip and knee pain: comparison to placebo and naproxen in two phase III studies (NCT00830063 & NCT00863304)

Abstract

Two placebo- and naproxen (500mg BID)-controlled multicenter studies evaluated efficacy and safety of tanezumab (5mg or 10mg intravenous, given at Weeks 0 and 8), a monoclonal antibody that inhibits nerve growth factor, in patients with moderate-to-severe knee or hip osteoarthritis. Efficacy was assessed at Week 16 with 3 co-primary endpoints (Western Ontario & McMaster Universities OA Index [WOMAC] Pain, WOMAC Physical Function, and Patient Global Assessment [PGA] of OA). To account for multiple comparisons, fixed sequence testing and Hochberg procedures required that the assessment of superiority for tanezumab 5 mg versus naproxen was dependent on first achieving superiority for all comparisons of tanezumab 5 mg and 10 mg versus placebo and tanezumab 10 mg versus naproxen. Tanezumab 5mg and 10mg provided superior efficacy versus placebo for all co-primary endpoints in both studies (P≤0.014). Overall, 9 of 12 contrasts for tanezumab versus naproxen were statistically significant including tanezumab 5mg versus naproxen across all co-primary endpoints in both studies; however, only comparisons in WOMAC Physical Function were declared superior to naproxen with tanezumab 5mg for both studies since tanezumab 10mg failed to show consistent superiority over naproxen in WOMAC Pain & PGA. Adverse events (AEs) and withdrawals due to AEs were more common with active treatments than placebo; rates of serious AEs were similar across treatments. The most frequent AEs (≥5% in any active group) were arthralgia, pain in extremity, paresthesia, and peripheral edema. Tanezumab 5mg was better tolerated than tanezumab 10mg in both studies. Six patients (4 placebo, 1 tanezumab 5mg, 1 naproxen) required total joint replacements (TJRs). The tanezumab OA clinical program is currently on clinical hold due to potential AEs leading to TJRs. In conclusion, these studies indicate tanezumab is efficacious in treating osteoarthritis pain and may provide patients greater symptomatic improvement than existing agents such as naproxen.