Abstract

Objective: To test whether RA trials treatment efficacy vs. control is better detected for patients with lower tender or swollen joint counts than for higher counts.

Methods: Using data from 6 large multicenter trials (N = 2002) and an intent to treat approach at 6 months, we created within each trial two subtrials, the lower disease activity group (defined by TJC <= overall median )and the higher disease activity group(TJC above median). The same approach was used for SJC . We tested for active treatment - control differences using several RA trial outcome measures: ACR20, EULAR response, ACRHybrid . We compared sample sizes needed for higher TJC and SJC RA trials vs. lower TJC and SJC trials, and explored consistency of results across trials and explanations for results by examining active treatment and control responses.

Results: We found that subtrials of subjects with lower TJC had much higher sensitivity to change than those of subjects with higher TJC across all trials and outcome measures. A trial with lower TJC patients would require a smaller sample size than ones with higher TJC patients. Results were not consistent for SJC subgroups. We found 3 reasons for sensitivity to change of lower TJC: 1) Compared to higher TJC, those with lower TJC showed greater response to active treatment. Subjects with higher TJC on control treatment had 2) greater % improvement and 3) more variable responses than those in the lower TJC group.

Conclusions: In RA trials, patients with lower disease activity within the range of current trial eligibility are more likely to show treatment efficacy than patients with higher disease activity. Lowering thresholds especially for TJC in trials may make it easier to detect treatment effects in RA.