Placebo response in psoriatic arthritis clinical trials: a systematic review and meta-analysis.

Abstract

OBJECTIVE\nTo determine the placebo response rate in psoriatic arthritis (PsA) randomised clinical trials (RCTs), its contributing factors, and impact on the effect size of active treatments.\n\n\nMETHODS\nWe searched multiple databases, from inception to December 20, 2020, for placebo-controlled RCTs in PsA. We used a random-effects meta-analysis to pool the response rates for the American College of Rheumatology 20 (ACR20) criteria in the placebo arm, determined the risk difference for treatment vs placebo, and used meta-regression to determine the factors associated with placebo response rates. The risk of bias was assessed in duplicate. PROSPERO: CRD42021226000.\n\n\nRESULTS\nWe included 42 RCTs (5,050 patients receiving placebo) published between 2000 and 2020; The risk of bias was low in 28 trials, high in four, and with some concerns in ten. The pooled placebo response rate was 20.3% (95% CI, 18.6% to 22.1%; predicted intervals, 11.7%-29.0%), with significant between-trial heterogeneity (I2=56.8%, p< 0.005). The pooled risk difference for treatment vs placebo was 27% (95%CI, 24% to 31%). In the multivariable meta-regression, there was a 15% (95% CI, 2.9% to 29.8%) increase in the odds of achieving the placebo response for each five-year increment in publication year (p= 0.016). In addition, the active treatment risk difference decreased for every five-year increment in publication year (β = -0.053; 95% CI -0.099 to -0.007; p= 0.024) but was not associated with the placebo response.\n\n\nCONCLUSION\nDespite increasing over time, the placebo response for ACR20 in PsA RCTs was not associated with the active treatment effect size.