Efficacy and safety of IV tanezumab in osteoarthritis hip and knee pain
Two randomized, double-blind, double-dummy, placebo- and naproxen-controlled (naproxen 500mg twice daily) multicenter studies evaluated the efficacy and safety of tanezumab 5mg or 10mg IV in patients with moderate-to-severe knee or hip osteoarthritis (OA).
Tanezumab was given at Weeks 0 and 8 and efficacy was assessed at Week 16 with three coprimary 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 5mg vs. naproxen was dependent on first achieving superiority for all comparisons of tanezumab10mg vs. placebo and then tanezumab 10mg vs. naproxen and tanezumab 5mg vs. placebo.
Evan Ekman, MD, from Southern Orthopaedic Sports Medicine, Columbia, SC, and colleagues reported that tanezumab 5mg and 10mg provided superior efficacy vs. placebo for all coprimary endpoints in both studies (P≤0.014). Overall, nine of 12 contrasts for tanezumab vs. naproxen were statistically significant, including tanezumab 5mg vs. naproxen across all coprimary 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 and PGA. In addition, secondary endpoints demonstrated that both tanezumab 5mg and 10mg provided greater improvements compared with placebo and naproxen for WOMAC Pain, Outcome Measures in Rheumatology-Osteoarthritis Research Society International Responder Index, and WOMAC Stiffness responses at Week 16. Outcomes of both studies suggest, however, that tanezumab 5mg is the optimal dose.
Adverse events (AE) and withdrawals due to AEs were more common with active treatments than with placebo. Rates of serious AEs were similar across treatment groups. 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.
The authors concluded that these studies indicate tanezumab is efficacious in treating osteoarthritis pain and may provide patients greater symptomatic improvement than existing agents such as naproxen.