Date: Monday, November 6, 2017
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
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.
To cite this abstract in AMA style:Birbara CA, Dabezies EJ, Burr AM, Fountaine RJ, Smith MD, Brown MT, West CR, Arends RH, Verburg KM. Efficacy and Safety of Subcutaneous Tanezumab in Patients with Knee or Hip Osteoarthritis (NCT01089725) [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/efficacy-and-safety-of-subcutaneous-tanezumab-in-patients-with-knee-or-hip-osteoarthritis-nct01089725/. Accessed February 17, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-subcutaneous-tanezumab-in-patients-with-knee-or-hip-osteoarthritis-nct01089725/