O06 Improvements in pain, function and health status with subcutaneous tanezumab compared with placebo in patients with OA: pooled analysis of two randomized controlled trials

Abstract

Background: Osteoarthritis (OA) causes pain, disability and impaired quality of life. Tanezumab, a monoclonal antibody against nerve growth factor, is in development for the management of OA pain. Two randomised, placebo-controlled studies with a primary aim of assessing the efficacy and safety of subcutaneously administered tanezumab were recently completed as part of a phase 3 OA programme, and the data reported, separately. Here we report pooled analyses of secondary efficacy outcomes from these two trials: Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) treatment response and EuroQol 5 Dimension (EQ-5D-5L) questionnaire. Methods: Both studies enrolled patients with moderate-to-severe OA of the hip or knee, for whom standard care was inadequate or unsuitable. In study one (NCT02709486) with primary endpoint at Week 24, patients received three doses of placebo, tanezumab 2.5mg or tanezumab 5mg (at baseline/Week 8/Week 16). Study two was a dose-titration study (NCT02697773) with primary endpoint at Week 16, where patients received two doses of: placebo at baseline/Week 8 (pooled with study one placebo group), tanezumab 2.5mg at baseline/Week 8 (pooled with study one tanezumab 2.5mg group) or tanezumab 2.5mg at baseline/ tanezumab 5mg at Week 8 (pooled with study one tanezumab 5mg group). The current analysis assessed differences between pooled groups in OMERACT-OARSI treatment response, and EQ-5D-5L questionnaire responses and overall utility scores, at Week 16. Results: A total of 1,545 patients were evaluated. At Week 16 in the pooled analyses, more patients in the tanezumab 2.5mg (76.0%, 390/ 513) or tanezumab 5mg (77.4%, 400/517) groups than the placebo group (64.7%, 332/513) met the criteria for OMERACT-OARSI response (each p<0.0001 versus placebo). Patients in the pooled placebo, tanezumab 2.5mg and 5mg groups, respectively, recorded their baseline pain/discomfort (EQ-5D-5L) as none (1.8%, 1.0%, 0.6%), slight (7.6%, 9.7%, 8.9%), moderate (52.6%, 50.7%, 50.7%), severe (35.1%, 36.3%, 36.4%) or extreme (2.9%, 2.3%, 3.5%). At Week 16, patients recorded their pain/discomfort as none (12.8%, 15.4%, 15.8%), slight (37.3%, 44.3%, 44.8%), moderate (40.6%, 33.9%, 32.0%), severe (8.8%, 6.4%, 6.4%) or extreme (0.4%, 0.0%, 1.0%). Improvements in mobility, self-care, usual activities and anxiety/depression were also seen. At Week 16, the change from baseline in EQ-5D-5L utility score was greater for the pooled tanezumab 2.5mg group (difference in least squares means [95% confidence interval], 0.03 [0.01, 0.05], p=0.0083) or tanezumab 5mg group (0.04 [0.01, 0.06], p=0.0015) compared with placebo. Conclusion: Together, pooled analyses from these studies show that significant improvements in the composite measure OMERACTOARSI response are accompanied by significant improvements in overall health status as assessed by the EQ-5D-5L utility score at Week 16 for tanezumab-treated patients compared with placebo. These studies were sponsored by Pfizer and Eli Lilly and Company.