PT - JOURNAL ARTICLE AU - Katie Bechman AU - Mark Yates AU - Sam Norton AU - Andrew Cope AU - James B. Galloway TI - Placebo response in rheumatoid arthritis clinical trials AID - 10.3899/jrheum.190008 DP - 2019 May 01 TA - The Journal of Rheumatology PG - jrheum.190008 4099 - http://www.jrheum.org/content/early/2019/04/24/jrheum.190008.short 4100 - http://www.jrheum.org/content/early/2019/04/24/jrheum.190008.full AB - Objective Understanding the placebo response is critical to interpreting treatment efficacy, particularly for agents with a ceiling to their therapeutic effect, where an increasing placebo response makes it harder to detect potential benefit. The objective of this study is to assess the change in placebo responses over time in RA randomised placebo control trials (RCT) for drug licencing authorisation. Methods The Cochrane Controlled Trials Register database was searched to identify RCTs of biological or targeted synthetic DMARDs in RA. Studies were excluded if patients were: csDMARD naïve, not receiving background csDMARD therapy or were biologic experienced. Meta-regression model was used to evaluate changes in ACR20, ACR50 and ACR70 treatment response over time. Results There were 32 trials in total; anti-TNF therapy (n=15), tocilizumab (n=4), abatacept (n=2), rituximab (n=2) and JAK inhibitors (n=6). From 1999 to 2018, there was no significant trend in the age or gender of patients in the placebo arm. Disease duration, swollen joint count and DAS28-ESR at baseline all significantly reduced over time. There was a statistically significant increase in placebo ACR50 and ACR70 responses (ACR50 β=0.41, 95 CI 0.09 to 0.74, p=0.01; ACR70 β=0.18, 95 CI 0.04 to 0.31, p=0.01), that remained significant after controlling for potential confounders. Conclusion There has been a rise in the placebo response in RA clinical trials over the last two decades. Shifting RA phenotype, changes in trial design and expectation bias are possible explanations for this phenomenon. This observation has important implications when evaluating newer novel agent against established therapies.