Non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 inhibitors, in osteoarthritic knee pain: meta-analysis of randomised placebo controlled trials

Abstract

Objective To estimate the analgesic efficacy of non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclo-oxygenase-2 inhibitors (coxibs), in patients with osteoarthritis of the knee. Design Systematic review and meta-analysis of randomised placebo controlled trials. Studies reviewed 23 trials including 10 845 patients, median age of 62.5 years. 7807 patients received adequate doses of NSAIDs and 3038 received placebo. The mean weighted baseline pain score was 64.2 mm on 100 mm visual analogue scale (VAS), and average duration of symptoms was 8.2 years. Main outcome measure Change in overall intensity of pain. Results Methodological quality of trials was acceptable, but 13 trials excluded patients before randomisation if they did not respond to NSAIDs. One trial provided long term data for pain that showed no significant effect of NSAIDs compared with placebo at one to four years. The pooled difference for pain on visual analogue scale in all included trials was 10.1 mm (95% confidence interval 7.4 to 12.8) or 15.6% better than placebo after 2-13 weeks. The results were heterogeneous, and the effect size for pain reduction was 0.32 (0.24 to 0.39) in a random effects model. In 10 trials that did not exclude non-responders to NSAID treatment the results were homogeneous, with an effect size for pain reduction of 0.23 (0.15 to 0.31). Conclusion NSAIDs can reduce short term pain in osteoarthritis of the knee slightly better than placebo, but the current analysis does not support long term use of NSAIDs for this condition. As serious adverse effects are associated with oral NSAIDs, only limited use can be recommended.

Onset and durability of pain relief in knee osteoarthritis: Pooled results from two placebo trials of naproxen/esomeprazole combination and celecoxib

“…In the most recently published network meta-analysis of pain response with various pharmacologic interventions, the Hedges' g WOMAC pain effect sizes at 12 weeks for NAP and CEL versus placebo were 0.38 and 0.33, respectively [29]. Data from the pooled NAP/ESO trials in the present analysis confirm that maximal NSAID effectiveness occurs early in therapy and refute some prior studies suggesting that the pain effect of oral NSAIDs is limited to the first 2 to 3 weeks [ 47,48]. WOMAC pain effect sizes in the pooled NAP/ESO analyses generally were similar to those reported in other meta-analyses.…”

“…Similarly, effect sizes ranging from 0.20 to 0.45 were reported for CEL trials [47]. Pooled effect sizes for pain reduction with NSAIDs overall were 0.32 (0.24-0.39) across all trials and 0.23 (0.15-0.31) in 10 trials in which non-responders were not excluded [47]. In another meta-analysis based on a minimum clinically significant threshold of WOMAC pain improvement (defined as 9.7 mm), pooled NSAID response overall was 10.2 mm; however, no therapies had effect sizes that exceed the mean threshold for minimally clinical important improvement in the short-term or long-term [48].…”

“…Effect sizes are one method for comparing data across trials, and several meta-analyses have reported effect sizes for WOMAC pain response with various analgesics [29,[47][48][49]. In a 2004 study, effect sizes ranging from 0.27 to 0.37 were reported for randomized controlled trials involving NAP [47].…”

“…In a 2004 study, effect sizes ranging from 0.27 to 0.37 were reported for randomized controlled trials involving NAP [47]. Similarly, effect sizes ranging from 0.20 to 0.45 were reported for CEL trials [47]. Pooled effect sizes for pain reduction with NSAIDs overall were 0.32 (0.24-0.39) across all trials and 0.23 (0.15-0.31) in 10 trials in which non-responders were not excluded [47].…”

Meta-analysis: Acupuncture for Osteoarthritis of the Knee

“…However, according to a recent systematic review (8), NSAIDs are only slightly better than placebo in providing shortterm pain relief and their effects are probably too small to be meaningful to patients (8). Furthermore, many NSAIDs are associated with considerable side effects (9).…”