Background/Purpose : Tanezumab (TNZ) is a monoclonal antibody that inhibits nerve growth factor and reduces hip or knee osteoarthritis (OA) pain. A placebo-controlled phase 3 study (NCT01089725), evaluated efficacy of subcutaneous (SC) TNZ (2.5, 5, and 10 mg) and compared therapeutic equivalence of TNZ 10 mg SC to TNZ 10 mg intravenous (IV) every 8 weeks in the treatment of symptomatic OA. Co-primary endpoints were Western Ontario and McMaster Universities (WOMAC) OA Pain and Physical Function Indices and Patient’s Global Assessment of OA (PGAOA) at Week 8.

Methods: Patients (N=379) with knee or hip OA were randomized and treated with placebo (n=72), TNZ 2.5 mg SC (n=74), 5 mg SC (n=63), 10 mg SC (n=86) or 10 mg IV (n=84) every 8 weeks. Efficacy analyses included change from baseline in WOMAC Pain and Physical Function subscales, PGAOA, and percentage of patients with ≥30%, ≥50%, ≥70%, and ≥90% improvement in WOMAC Pain. Safety assessments included adverse event (AE) reporting, 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; thus no statistical testing was conducted. Since <10% of patients received a second dose at Week 8, efficacy results are described for change from baseline to Week 8 only. Mean (standard error [SE]) change from baseline to Week 8 in WOMAC Pain in TNZ groups ranged from −3.59 (0.26) to −3.89 (0.32); versus −2.74 (0.25) with placebo. Percentage of patients with ≥30%, ≥50%, ≥70%, and ≥90% reductions in WOMAC Pain score at Week 8 was greater in all TNZ groups versus placebo (Figure). Mean (SE) change from baseline to Week 8 in WOMAC Physical Function ranged from −3.13 (0.25) to −3.51 (0.28) with TNZ and −2.26 (0.24) with placebo. For PGAO, mean (SE) change from baseline to Week 8 was −0.90 (0.11) to −1.08 (0.12) with TNZ and −0.78 (0.10) with placebo. Inspection of the efficacy-time curves indicated that onset and duration of analgesia with all SC doses were similar to the 10-mg IV dose over the 8-week dosing interval. Overall incidence of all-causality AEs was highest with TNZ 10-mg IV (52.4%) and placebo (51.4%). No AEs of osteonecrosis were reported by investigators. Two placebo-treated patients and 3 TNZ 2.5-mg SC patients underwent total joint replacements. AEs in ≥5% of patients in any treatment group included arthralgia, paresthesia, hypoesthesia, worsening OA, headache, and joint swelling; paresthesia and hypoesthesia occurred only in patients receiving TNZ. Injection site reactions were reported by 4.7%, 3.6%, 2.8%, 2.7% and 0% of those treated with TNZ 10 mg SC, TNZ 10 mg IV, placebo, TNZ 2.5 mg SC and TNZ 5 mg SC, respectively and the majority were mild (none were severe).

Conclusion: SC TNZ provided improvements in Pain, Physical Function, and PGAOA at all doses. Efficacy and safety of SC TNZ were generally similar to IV in patients with OA pain.