Background/Purpose : Tanezumab (TNZ), a monoclonal antibody that inhibits nerve growth factor, reduces hip or knee osteoarthritis (OA) pain. A non-controlled, randomized, double-blind study of TNZ 2.5, 5, and 10 mg administered by subcutaneous (SC) injection at 8-week intervals was conducted in patients with hip or knee OA.

Methods: Patients (N=678) with moderate to severe knee or hip OA were randomized in a 1:1:1 ratio and treated with TNZ 2.5 mg (n=230), 5 mg (n=222), or 10 mg (n=226) every 8 weeks. Efficacy analyses included change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain and Physical Function subscales, Patient’s Global Assessment of OA (PGAO), and percentage of patients with ≥30%, ≥50%, ≥70%, and ≥90% improvement in WOMAC Pain. Safety assessments included adverse event (AE) documentation, physical and neurological examinations, and laboratory tests.

Results: The study discontinued prematurely due to a FDA partial clinical hold on TNZ non-cancer pain studies. Patients received 1 to 4 TNZ doses. Mean study treatment duration was 180, 191, and 187 days for TNZ 2.5, 5, and 10 mg treatment, respectively. TNZ 10 mg and TNZ 5 mg provided similar improvements from Baseline at Weeks 8 and 16 in WOMAC Pain, Physical Function, and PGAO; improvements were greater than with TNZ 2.5 mg. More patients had ≥30%, ≥50%, ≥70%, and ≥90% improvement in WOMAC Pain at Weeks 8 (Figure) and 16 with TNZ 10 and 5 mg than with TNZ 2.5 mg. Overall AE incidence was greatest with TNZ 10 mg (80.1%), followed by TNZ 5 mg (76.1%), and 2.5 mg (68.7%). The most frequently reported AEs were arthralgia, injection site reaction, and paresthesia. Osteonecrosis (ON) was reported as an AE in 4 patients (1.8%) treated with TNZ 10 mg, 4 patients (1.8%) in the TNZ 5 mg group, and 1 patient (0.4%) in the TNZ 2.5 mg group. Thirty-four patients had an all-cause total joint replacement. Of these, 22 (64.7%) events inclusive of the 9 cases of ON were subsequently adjudicated by a blinded external adjudication committee and none were adjudicated to primary ON. The percentage of patients with no new or worsened neurological examination abnormality at last assessment ranged from 82% to 88% across groups.

Conclusion: Overall, SC TNZ provided improvements in Pain, Physical Function, and PGAO at all doses. TNZ 5 and 2.5 mg were better tolerated than TNZ 10 mg.