AB0859 IMPROVEMENTS IN PHYSICAL FUNCTION IN PATIENTS WITH OSTEOARTHRITIS RECEIVING SUBCUTANEOUS TANEZUMAB IN 3 RANDOMIZED CONTROLLED TRIALS
Authors: S. P. Stanos, W. J. Chang, C. Hultman, M. Sadrarhami, T. Yamabe, P. Park
Journal: Annals of the Rheumatic Diseases (2020)

Background: Tanezumab, a monoclonal antibody against nerve growth factor, is in development for the treatment of the signs and symptoms of osteoarthritis (OA). Objectives: To assess the improvement in physical function following treatment with subcutaneous (SC) tanezumab in three Phase 3 OA studies. Methods: All three randomized, double-blind, controlled studies enrolled patients (pts) with radiographically-confirmed OA of the hip or knee, who had inadequate response or could not tolerate standard of care analgesics. Study 1 was a dose-titration study ( NCT02697773 ), where pts received two SC doses of: placebo at baseline/week (wk) 8; tanezumab 2.5 mg at baseline/wk 8; or tanezumab 2.5 mg at baseline/5 mg at wk 8 1 . In Study 2 ( NCT02709486 ), pts received three SC doses of placebo, tanezumab 2.5 mg, or 5 mg (at baseline/wk 8/wk 16). In Study 3 ( NCT02528188 ), pts received a stable dose of nonsteroidal anti-inflammatory drugs (NSAIDs) before randomization to double-dummy tanezumab 2.5 mg or 5 mg (at baseline and every 8 wks during a 56 wk treatment period) or twice daily oral NSAIDs. Pts completed Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function subscale questionnaires in clinic. The least squares (LS) mean (standard error (SE)) change from baseline was calculated for each timepoint up to wk 16 and significance was calculated versus placebo (Studies 1 and 2) or NSAID (Study 3). Results: A total of 4541 pts were evaluated (n=696 in Study 1, n=849 in Study 2 and n=2996 in Study 3). In Studies 1 and 2, there were statistically significant improvements from baseline for all tanezumab treated groups versus placebo at wks 2, 4, 8, 12 and 16 ( Table 1 ). In Study 3, the tanezumab 2.5 mg group showed a significant improvement from baseline at wk 2, compared with the NSAID group ( Table 2 ). At wk 4, both tanezumab treatment groups showed a significant improvement from baseline compared with the NSAID group ( Table 2 ). The tanezumab 5 mg group showed a significant improvement from baseline compared with the NSAID group at wks 8 and 16 ( Table 2 ). Table 1. Change from baseline in WOMAC Physical Function: Study 1 and 2 Study 1 Study 2 Tanezumab 2.5 mg n=231 Tanezumab 2.5/5 mg n=233 Placebo n=232 Tanezumab 2.5 mg n=283 Tanezumab 5 mg n=284 Placebo n=282 Wk 2 LS mean (SE) -2.89 (0.21) -3.05 (0.21) -2.14 (0.21) -1.95 (0.14) -1.69 (0.14) -1.26 (0.14) p vs placebo 0.0004 &lt;0.001 &lt;.0001 0.0014 Wk 4 LS mean (SE) -3.30 (0.21) -3.38 (0.21) -2.28 (0.21) -2.52 (0.15) -2.50 (0.15) -1.71 (0.15) p vs placebo &lt;.0001 &lt;.0001 &lt;.0001 &lt;.0001 Wk 8 LS mean (SE) -3.17 (0.21) -3.12 (0.21) -2.55 (0.21) -2.38 (0.15) -2.52 (0.15) -1.76 (0.15) p vs placebo 0.0057 0.0114 &lt;.0001 &lt;.0001 Wk 12 LS mean (SE) -3.61 (0.22) -3.80 (0.22) -2.75 (0.22) -2.83 (0.16) -2.87 (0.16) -2.04 (0.16) p vs placebo 0.0004 &lt;.0001 &lt;.0001 &lt;.0001 Wk 16 LS mean (SE) -3.22 (0.22) -3.45 (0.22) -2.56 (0.22) -2.68 (0.16) -2.69 (0.16) -2.02 (0.17) p vs placebo 0.0065 0.0002 &lt;.0001 &lt;.0001 Table 2. Change from baseline in WOMAC Physical Function in Study 3 Tanezumab 2.5 mg n=1002 Tanezumab 5 mg n=998 NSAID n=996 Wk 2 LS mean (SE) -1.76 (0.08) -1.64 (0.08) -1.55 (0.08) p vs NSAID 0.0150 0.3286 Wk 4 LS mean (SE) -2.29 (0.09) -2.31 (0.09) -1.96 (0.09) p vs NSAID 0.0004 0.0001 Wk 8 LS mean (SE) -2.46 (0.10) -2.69 (0.10) -2.27 (0.10) p vs NSAID 0.0517 &lt;.0001 Wk 16 LS mean (SE) -3.27 (0.11) -3.39 (0.11) -3.08 (0.11) p vs NSAID 0.0691 0.0030 Conclusion: Consistent improvements in WOMAC Physical Function were seen across the first 16 wks for all dose groups of tanezumab-treated pts versus placebo in Study 1 and 2. The tanezumab 5 mg group in Study 3 showed a significant improvement at wks 4, 8 and 16 compared with the NSAID group. Improving physical function could help OA pts attain treatment goals beyond pain relief, improving their ability to perform important daily activities. References: [1]Schnitzer, T. J. et al . JAMA 2019 Disclosure of Interests: Steven P Stanos Consultant of: Pfizer, Sanofi, Scilex, Salix, Speakers bureau: Scilex, Wilson J Chang: None declared, Cory Hultman Employee of: Eli Lilly and Co., Mojgan Sadrarhami Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., Takaharu Yamabe Shareholder of: Pfizer, Employee of: Pfizer, Peter Park Shareholder of: Pfizer Inc., Employee of: Pfizer Inc.