Short-term placebo response in trials of patients with symptomatic osteoarthritis: differences between hip and knee

In placebo-controlled RCT of symptomatic treatment in osteoarthritis (OA) the extent of pain reduction is heterogeneous, the pooled effect size rather small. Pain reduction is typically higher in knee than in hip trials. The recommended trial duration is 3 months, but in knee OA the best treatment effect vs placebo is observed at 2 weeks. We hypothesized that the placebo response differs in knee vs hip OA.

We performed a meta-analysis to describe the time course of pain in placebo groups of trials in knee and hip OA over 3 months.

A systematic search of PubMed, MEDLINE and Google Scholar of placebo-controlled cox-2 inhibitor (coxib) RCT (from 1999 to 2007) of hip and knee OA was performed. Pain levels (visual analogue scale [VAS], Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) in the placebo groups at different measurement time points were extracted, expressed as weighted mean at weeks 2, 4, 6-8 and 12-13.

Twenty-one studies included 3064 knee OA patients and 608 hip OA patients. For knee OA, pain (VAS) decreased from 15 mm at week 2, to 20 mm at week 6-8, and 21 mm at week 12-13. For hip OA patients, pain decreased by 12 mm, 14 mm and 14 mm, respectively.

Pain decreased in both knee and hip OA patients treated with placebo at 2 weeks, but further decreases up to week 12 occurred only in knee OA, especially for pain VAS, resulting in a time dependent impact on the magnitude of treatment outcome. Primary endpoint pain should be assessed at 2-4 weeks.