56 - Efficacy of Subcutaneous Tanezumab for the Treatment of Osteoarthritis Across Body Mass Index Groups: A Subgroup Analysis of Pooled Data from Two Randomized, Placebo-Controlled Trials

¹Sorbonne Université, INSERM, AP-HP Hospital Saint Antoine, Paris, France. ²University of California, San Diego, California, USA. ³Lansing Rheumatology, East Lansing, Michigan, USA. ⁴Eli Lilly and Company, Indianapolis, Indiana, USA. ⁵Pfizer Inc., New York, New York, USA

Purpose
Tanezumab is a monoclonal antibody against nerve growth factor with efficacy in the treatment of osteoarthritis (OA). Higher body mass index (BMI) can reduce the effectiveness of some drugs. This pooled, post-hoc, subgroup analysis explored the efficacy of subcutaneous tanezumab in patients with OA and differing BMI.
Methods
A pooled exploratory analysis of patient level data from two randomized, placebo-controlled, Phase 3 trials (NCT02697773 and NCT02709486) of subcutaneous tanezumab (2.5 mg or 5 mg every 8 weeks for 16 or 24 weeks) in patients aged ≥18 years with moderate-to-severe knee or hip OA. In one trial, tanezumab was titrated from 2.5 mg at baseline to 5 mg at Week 8. This data is included in the pooled 5 mg group. Co-primary endpoints were change from baseline in Western Ontario and McMaster Universities OA Index (WOMAC) Pain (0 to 10; increasing pain), WOMAC Physical Function (0 to 10; increasing difficulty), and Patient Global Assessment of OA (PGA-OA; 1 to 5; poorer assessment) scores. Results are presented as LS mean change from baseline versus placebo at Week 16 with 95% confidence interval. This exploratory post-hoc analysis was not part of the pre-specified hypothesis testing plan or included in any sample size calculations (leading to possibly low or uneven n); therefore, comparisons between treatment or BMI subgroups (<25; 25 – 30, 30 - <35, and ≥35 kg/m²) should be conducted with caution.
Results
In the overall pooled population, comprising patients of all BMIs, both tanezumab doses were associated with improved WOMAC Pain, WOMAC Physical Function, and PGA-OA scores at Week 16 compared with placebo (all p<0.05).Similar improvements vs placebo were observed for all three outcomes, irrespective of BMI(grouped as<25 [placebo n = 51; 2.5 mg n = 72; 5 mg n = 64], 25─<30 [165; 162; 169], 30─<35 [167; 172; 183], and≥35 [130; 107; 101]).In the pooled population, change in LS mean WOMAC Pain score over placebo (n = 513) was -0.7 (-0.95, -0.37) and -0.7 (-0.99, -0.41) in the 2.5 mg (n = 513) and 5 mg (n = 517) tanezumab groups, respectively. In the BMI subgroups, change over placebo ranged from -0.6 to -0.9 for both tanezumab doses (all p<0.05 [unadjusted] except for 5 mg in the <25kg/m² subgroup and both doses in the≥35 kg/m² subgroup). In the pooled population, change in LS mean WOMAC physical function score over placebo was -0.7 (-1.00, -0.42) and -0.8 (-1.08, -0.50) in the 2.5 mg and 5 mg tanezumab groups. In the BMI subgroups, change in over placebo ranged from -0.6 to -0.9 for both tanezumab doses (all p<0.05 [unadjusted] except for 5 mg in the <25kg/m² subgroup). In the pooled population, change in LS mean PGA-OA score over placebo was -0.2 (-0.30, -0.09) and -0.3 (-0.36, -0.15) in the 2.5 mg and 5 mg tanezumab groups. In the BMI subgroups, change over placebo ranged from -0.1 to -0.3 for both tanezumab doses (p>0.05 [unadjusted] except for 5 mg in the 25─30 kg/m2 and≥35 kg/m2 subgroups).
Conclusions
This exploratory analysis indicates that patient BMI does not influence the improvements in OA associated with short-term subcutaneous tanezumab use.