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
Francis Berenbaum1, Bill McCarberg2, Iris Zink3, Claudia Rivera-Salas3, Jerry Hall4, Mojgan Sadrarhami5, Ruoyong Yang5
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.