Tanezumab for the Treatment of Pain from Osteoarthritis of the Knee

TLDR

Increased expression of nerve growth factor in injured or inflamed tissue is linked to heightened pain. This proof‑of‑concept study aimed to evaluate the safety and analgesic efficacy of tanezumab, a humanized monoclonal antibody that inhibits nerve growth factor, in patients with knee osteoarthritis. Patients were randomized to receive multiple doses of tanezumab or placebo, and efficacy was assessed by knee pain while walking, global response, WOMAC scores, and OMERACT‑OARSI criteria, with safety monitored throughout. Tanezumab produced 45–62% reductions in knee pain versus 22% with placebo, improved global response by 29–47% versus 19%, achieved 74–93% OMERACT‑OARSI response versus 44%, and was associated with mild to moderate adverse events (headache 9%, URTI 7%, paresthesia 7%) at a 68% incidence versus 55% for placebo. The trial was funded by Rinat Neuroscience and registered at ClinicalTrials.gov (NCT00394563).

Abstract

Increased expression of nerve growth factor in injured or inflamed tissue is associated with increased pain. This proof-of-concept study was designed to investigate the safety and analgesic efficacy of tanezumab, a humanized monoclonal antibody that binds and inhibits nerve growth factor.We randomly assigned 450 patients with osteoarthritis of the knee to receive tanezumab (administered at a dose of 10, 25, 50, 100, or 200 μg per kilogram of body weight) or placebo on days 1 and 56. The primary efficacy measures were knee pain while walking and the patient's global assessment of response to therapy. We also assessed pain, stiffness, and physical function using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); the rate of response using the criteria of the Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT-OARSI); and safety.When averaged over weeks 1 through 16, the mean reductions from baseline in knee pain while walking ranged from 45 to 62% with various doses of tanezumab, as compared with 22% with placebo (P<0.001). Tanezumab, as compared with placebo, was also associated with significantly greater improvements in the response to therapy as assessed with the use of the patients' global assessment measure (mean increases in score of 29 to 47% with various doses of tanezumab, as compared with 19% with placebo; P≤0.001). The rate of response according to the OMERACT-OARSI criteria ranged from 74 to 93% with tanezumab treatment, as compared with 44% with placebo (P<0.001). The rates of adverse events were 68% and 55% in the tanezumab and placebo groups, respectively. The most common adverse events among tanezumab-treated patients were headache (9% of the patients), upper respiratory tract infection (7%), and paresthesia (7%).In this proof-of-concept study, treatment with tanezumab was associated with a reduction in joint pain and improvement in function, with mild and moderate adverse events, among patients with moderate-to-severe osteoarthritis of the knee. (Funded by Rinat Neuroscience; ClinicalTrials.gov number, NCT00394563.).