Gender, age, disease severity, body mass index and diabetes may not affect response to subcutaneous tanezumab in patients with osteoarthritis after 16 weeks of treatment. A subgroup analysis of placebo-controlled trials

Abstract

Aim: To assess the impact of pre-specified patient characteristics on efficacy and safety of subcutaneous tanezumab in patients with osteoarthritis (OA).

Methods: Data were pooled from two (efficacy; N = 1545) or three (safety; N = 1754) phase 3 placebo-controlled trials. Change from baseline to week 16 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain, WOMAC Physical Function and patient global assessment of OA (PGA-OA) scores was compared between tanezumab (2.5 and 5 mg) and placebo groups via analysis of covariance. Treatment-emergent adverse events (TEAEs) were summarised descriptively. Analyses were done in patient subgroups (men or women; age <65, ≥65, or ≥75 years; body mass index [BMI] <25, 25 to <30, 30 to <35 or ≥35 kg/m² ; diabetes or no diabetes; baseline WOMAC Pain score <7 or ≥7; and Kellgren-Lawrence [KL] grades 2, 3 or 4 in the index joint) and the overall population.

Results: In all subgroups, improvements in WOMAC Pain were numerically greater and often statistically significant (P < .05) for both tanezumab groups compared with placebo. Results were similar for WOMAC Physical Function and PGA-OA. TEAE profiles were generally consistent across subgroups and similar to the overall population (ie slightly higher rates of TEAEs, serious TEAEs and severe TEAEs with tanezumab relative to placebo) with a few exceptions. Exceptions included women reporting slightly more TEAEs with tanezumab than men, and patients with diabetes reporting slightly more severe TEAEs with tanezumab than patients without diabetes. Additionally, TEAEs were more frequent with tanezumab than placebo in the age ≥65 and ≥75 years, but not the age <65 years, subgroups.

Conclusions: Efficacy and safety/tolerability of tanezumab may not be meaningfully impacted by gender, age, BMI, diabetes status, baseline pain severity or KL grade in the index joint. Conclusions are limited by low patient number in some subgroups. Clinicaltrials.gov: NCT02697773, NCT02709486, NCT01089725.

FIGURE 1

Change in WOMAC Pain^† from baseline to week 16 (NCT02697773 and NCT02709486). Symbols: ○ = tanezumab 2.5 mg; ● = tanezumab 5 mg. ^†Scores range from 0 to 10, with higher scores indicating greater pain severity. ^‡Patients were included in the diabetes group if they had a medical history of hyperglycaemia, type 1 or type 2 diabetes mellitus, or a baseline haemoglobin A1c ≥6.5%. ^§In the index joint; defined as the most painful joint at screening with a qualifying WOMAC Pain score and KL grade as confirmed by a central reader. N represents the number of patients, with available baseline data, included in the analysis. *P < .05 vs placebo. BMI, body mass index; CI, confidence interval; KL, Kellgren‐Lawrence; LS, least squares; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index

FIGURE 2

Proportion of patients achieving ≥50% improvement in WOMAC Pain^† from baseline to week 16 (NCT02697773 and NCT02709486). Symbols: ○ = tanezumab 2.5 mg; ● = tanezumab 5 mg. ^†Scores range from 0 to 10, with higher scores indicating greater pain severity. ^‡Patients were included in the diabetes group if they had a medical history of hyperglycaemia, type 1 or type 2 diabetes mellitus, or a baseline haemoglobin A1c ≥6.5%. ^§In the index joint; defined as the most painful joint at screening with a qualifying WOMAC Pain score and KL grade as confirmed by a central reader. N represents the number of patients, with available baseline data, included in the analysis. *P < .05 vs placebo. BMI, body mass index; KL, Kellgren‐Lawrence; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index