Effect of the Application of Trial Inclusion Criteria on the Efficacy of Adalimumab Therapy in a Rheumatoid Arthritis Cohort

Objective. To evaluate the influence of inclusion criteria used in rheumatoid arthritis (RA) trials with adalimumab on clinical outcome and response. Methods. The different inclusion criteria of published trials of adalimumab in RA were separately applied to a large prospective cohort of patients with RA treated with adalimumab (AdRA cohort), thereby mimicking patient selection for a clinical trial. Clinical response and outcome in the resulting 11 projection groups were compared using the 28-joint Disease Activity Score (DAS28) and time-averaged DAS28 as outcome measures of efficacy. Results. Thirteen trials (n = 54-799) with 11 different sets of entry criteria were identified, resulting in 11 projection groups (n = 22-168). The DA528 at baseline was similar in the original trial and each projection group based on this trial (5.1-6.4, total AdRA cohort 5.1). After 28 weeks, the efficacy varied substantially among the 11 projected groups (change from baseline DAS28: -1.65 to -2.65, time-averaged DAS28 3.67-4.53). Expressed as outcome (DA528 at 28 weeks), the efficacy was much more similar for almost all projection groups (3.5-4.0) and thus appeared to be mostly independent of disease activity at baseline. Conclusion. We observed that different inclusion criteria for clinical trials can have a marked effect on the expected response, i.e., improvement from baseline. A novel finding is that final disease activity appeared much less dependent on initial disease activity. Our study suggests that for daily practice, one can assume that adalimumab treatment will on average result in a DAS28 between 3.5 and 4.0 after 28 weeks of treatment, regardless of baseline disease activity. (First Release June 15 2011; J Rheumatol 2011;38:1884-90; doi:10.3899/jrheum.101283)