Phenotypic Factors and Celecoxib Efficacy in Knee OA: A Post‑hoc Pooled Analysis of Two Randomized, Double‑Blind, Placebo‑Controlled Trials.

INTRODUCTION

Knee osteoarthritis (OA) is a major cause of disability worldwide and disproportionately affects women and individuals with obesity. Treatment response might vary by sex and body mass index (BMI). This study assessed whether celecoxib pain reduction differs across sex (male versus female) or BMI (obese ≥ 30 kg/m2 versus nonobese < 30 kg/m2) in knee OA patients, using change from baseline in Visual Analog Scale (VAS) pain at Week 6 as primary endpoint.

METHODS

This post hoc pooled analysis included two randomized, double-blind, placebo-controlled trials (NH49-96-02-060; NH49-98-02-087). Adults with knee OA flare and baseline VAS pain ≥ 40 mm received placebo, 100 mg of celecoxib twice daily (BID), or 200 mg once daily (OD) for 6 weeks. Mild baseline pain was excluded to align with original trial criteria. The full analysis set (FAS) included patients with ≥ 1 dose and ≥ 1 post-baseline assessment. Primary subgroups were assessed using analysis of covariance (ANCOVA) with last observation carried forward (LOCF) for missing data, with longitudinal evaluation at Week 2 and 6 using mixed model for repeated measures (MMRM). Sensitivity analyses using alternative imputation methods were also performed.

RESULTS

A total of 1360 participants (427 men, 933 women) were included. Baseline VAS pain score was higher in women and patients with obesity (both p < 0.0001), who also showed greater placebo response. At Week 6, both celecoxib regimens significantly reduced pain versus placebo across sex and BMI subgroups. Women had greater observed pain reductions with similar efficacy between sexes, and obese participants showed comparable benefit with both doses. Similar findings were observed in MMRM analyses. Celecoxib provided rapid, sustained OA pain relief across the two subpopulations.

CONCLUSIONS

100 mg of celecoxib BID and 200 mg OD showed consistent analgesic efficacy across sex and BMI subgroups, despite higher baseline pain and stronger placebo response in women and obese participants. These findings support the use of either regimen across diverse OA patient profiles and suggest that baseline pain differences do not necessarily reduce response to cyclooxygenase (COX)-2 inhibition.