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
Authors: Walsh David , Schnitzer Thomas J , Berenbaum Francis , Howland Samantha , Wilhelm Stefan , Junor Rod 
Published: April 2020

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 2.5 mg or tanezumab 5 mg (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 2.5 mg at baseline/Week 8 (pooled with study one tanezumab 2.5 mg group) or tanezumab 2.5 mg at baseline/tanezumab 5 mg at Week 8 (pooled with study one tanezumab 5 mg 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 2.5 mg (76.0%, 390/513) or tanezumab 5 mg (77.4%, 400/517) groups than the placebo group (64.7%, 332/513) met the criteria for OMERACT-OARSI response (each p &lt; 0.0001 versus placebo). Patients in the pooled placebo, tanezumab 2.5 mg and 5 mg 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 2.5 mg group (difference in least squares means [95% confidence interval], 0.03 [0.01, 0.05], p = 0.0083) or tanezumab 5 mg 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 OMERACT-OARSI 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.

Disclosures
D. Walsh: Consultancies; consulting fees (non-personal, pecuniary interest) from Pfizer, Lilly, GlaxoSmithKline, AbbVie, Medscape Education, Love Productions. T.J. Schnitzer: Consultancies; TJS has received consulting fees from Pfizer, Lilly, AbbVie, Aptinyx, Genzyme, Regeneron, and Vertex. Grants/research support; TJS has engaged in clinical research for AbbVie, Grünenthal, and Radius. F. Berenbaum: Consultancies; Consulting fees/remuneration from AbbVie, Merck, Regulaxis, 4P Pharma, Bone Therapeutics, Galapagos, Peptinov, Expanscience, Flexion, Janssen, MerckSerono, Novartis, Roche, Gilead, Sanofi, GlaxoSm. S. Howland: Corporate appointments; SH is an employee of Pfizer Ltd. Shareholder/stock ownership; SH holds Pfizer stock options. S. Wilhelm: Corporate appointments; SW is a Lilly employee. Shareholder/stock ownership; SW holds Lilly stock and/or stock options. R. Junor: Corporate appointments; RJ is an employee of Pfizer Ltd. Shareholder/stock ownership; RJ holds Pfizer stock and/or stock options.