Background/Purpose: Nerve growth factor (NGF) levels are associated with increased pain perception and are elevated in joints of arthritis patients. Tanezumab, a humanized monoclonal antibody, inhibits NGF with high specificity and affinity. A non-controlled, randomized, dose-blinded extension study (NCT00809783) following placebo-controlled and active comparator, multiple-dose, Phase III parent studies was conducted to evaluate long-term efficacy and safety of tanezumab in patients with osteoarthritis (OA) of the knee or hip.

Methods: Patients were eligible to enroll up to 12 weeks after their last dose of study medication in the parent study. Patients (N=2142) received tanezumab 2.5 mg (n=522), 5 mg (n=832), or 10 mg (n=788) IV every 8 weeks up to 80 weeks. Safety assessments included adverse event documentation, physical and neurological examinations and laboratory tests. Efficacy analyses included change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain and Physical Function subscales and Patient’s Global Assessment of OA.

Results: Demographic characteristics were similar across treatments. Mean duration of combined parent and extension study treatment for tanezumab 2.5, 5, and 10 mg was 353, 345, and 335 days, respectively. The most frequently reported treatment-related adverse events were paresthesia, arthralgia and hypoesthesia. Osteonecrosis was reported for 28 (1.3%) patients, only one event subsequently was adjudicated as osteonecrosis. Concomitant non-steroidal anti-inflammatory drugs (NSAIDs) use was associated with increased incidence of rapidly progressive osteoarthritis. A total of 187 patients (8.7%) underwent total joint replacements (TJR). All-cause TJR frequency was 5.2% in those not taking NSAIDs (n=1173) vs.13.0% in the concomitant NSAID cohort (n=969). Patients from tanezumab groups in the parent studies reported sustained improvement in WOMAC pain in the extension study (Figure). Few patients (7.2%) discontinued due to lack of efficacy indicating that treatment had a persistent beneficial effect. Similar results were observed for other efficacy endpoints.

Conclusion: Repeated doses of tanezumab 2.5 mg, 5 mg, and 10 mg every 8 weeks were efficacious and generally safe with no new safety signals identified. Persistent beneficial efficacy similar to that observed in the parent studies was demonstrated and maintained in OA patients over the long term.