Background Placebo effect has been referred as the contextual effect that surrounds the delivery of a treatment. It has been shown to improve pain in various clinical conditions and operates initially via central mechanisms. The placebo effect significantly contributes to the overall therapeutic effect of a treatment and can be influenced by various factors. However, the magnitude of placebo effect has yet to be determined in rheumatoid arthritis.
Objectives To determine the magnitude of placebo response for pain and other outcomes in randomised controlled trials (RCTS) in the treatment of rheumatoid arthritis and its possible determinants.
Methods A systematic review and meta-analysis was conducted of RCTS of non-steroidal anti-inflammatory drugs (NSAIDS), disease modifying anti-rheumatic drugs (DMARDS), biologics and complementary and alternative medicine (CAM). The quality of trials was assessed and any possible publication bias was determined by a funnel plot and Egger test. Effect size (ES) for placebo group was estimated as the standardized mean difference from baseline and was compared to the ES of the non-treatment group. All data were pooled using Hedges method in random effects model. Subgroup analysis was undertaken to investigate the determinants of the placebo effect. The proportion of placebo (contextual) effect (PCE) in the treatment of RA was also determined.
Results 165 RCTS representing 17,894 participants were included. The overall placebo ES for pain relief was 0.28 (95% CI 0.19, 0.37). The placebo analgesic effect varied with different treatments, for example: 0.30 (95% CI 0.02, 0.59) for NSAIDs; 0.34 (95% CI 0.18, 0.50) for biologics; 0.24 (95% CI 0.11, 0.38) for DMARDS; and 0.27 (95% CI 0.20, 0.37) for CAM. Placebo was also significantly effective in improving other outcomes such as the physician and patient assessment of the disease, tender joint count, swollen joint count and function. The ES for pain relief was higher in cross-over trials, trials with larger sample size and higher frequency of clinic visits and in participants with shorter disease duration. The PCE for RA varied from 0.42 (95% CI 0.35, 0.51) for CRP up to 0.63 (95% CI 0.57, 0.68) for pain.
Conclusions Placebo is effective in pain reduction in RA and also improves other outcomes. The placebo effect varies with different treatments, study design and participants' characteristic. This contextual effect accounts for up to 40% to 60% of the therapeutic benefit observed in RCTs of treatments in people with RA.
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Disclosure of Interest None declared
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