Rheumatology: Current Research
Open Access

Abstract

Meta-Analysis of Randomized Clinical Trials Investigating the Effect of TDT 064, a Gel-Based Formulation Containing Ultra-Deformable Phospholipid Vesicles, in Patients with Knee Osteoarthritis

Matthias Rother, Johannes Vester, Wolfgang W Bolten, Werner Kneer and Philip G Conaghan

Background: Ketoprofen-containing ultra-deformable phospholipid vesicles (IDEA-033) have been compared with drug-free vehicle (TDT 064) in randomized, controlled trials in knee osteoarthritis (OA). A pronounced treatment effect was reported for TDT 064, with an effect size (ES) comparable with celecoxib in one trial. Our meta-analysis determined whether these TDT 064 effects are beyond any expected placebo effect.

Methods: Five randomized, placebo-controlled studies of IDEA-033 in knee OA using TDT 064 as a control were included. Change from baseline in Western Ontario and McMaster Universities (WOMAC) OA Index pain and function subscale scores from each study were standardized and the ES calculated at various times. We compared our results with previously reported data on placebo response using similar methodology in a meta-analysis of 198 randomized OA trials.

Results: ES for pain relief at Week 6 was markedly higher for TDT 064 studies (ES: 1.04 [95% confidence interval (CI): 0.98–1.09]) than that previously reported for placebos in knee OA (ES: 0.54 [95% CI: 0.49–0.60]), as was the ES for function improvement (ES: 0.93 [95% CI: 0.87–0.98] vs ES: 0.49 [95% CI: 0.44–0.54], respectively). Higher ES for pain relief for TDT 064 studies was also reported with prior oral nonsteroidal anti-inflammatory drugs (NSAIDs) exposure (ES: 1.00 [95% CI: 0.93–1.07]), and in patients with high (ES: 1.08 [95% CI: 1.00–1.17]) or low baseline pain (ES: 1.03 [95% CI: 0.95–1.11]).

Conclusions: The magnitude of the effect with TDT 064 indicates this is unlikely to be solely a result of a placebo response.