Regression to the mean using the disease activity score in eligibility and response criteria for prescribing TNF-α inhibitors in adults with rheumatoid arthritis

Objectives. When patients with rheumatoid arthritis (RA) are selected to start TNF-a inhibitors on the basis of high disease activity scores (DAS), some of the fall in DAS will be due to regression to the mean (RTM). We have assessed the extent to which such RTM explains DAS improvements on TNF-a inhibitors in routine clinical practice. Methods. We retrospectively evaluated DAS28 scores that had been recorded as part of routine assessment for two RA cohorts. (i) Thirty-five patients receiving TNF-a inhibitors who had been assessed when starting TNF-a inhibitors, 9-21 months prior and 1.5-6 months post-treatment. (ii) One hundred and seventy-seven clinic patients assessed twice, a year apart in the years immediately before the introduction of TNF-a inhibitors. Results. In patients receiving TNF-a inhibitors, mean DAS fell 1.8 (95% confidence interval [Cl] 1.3, 2.3) from baseline but only 0.9 (95% Cl 0.4, 1.4) from the previous routine assessment. Twenty-four (69%) patients showed a fall in DAS of >1.2 from baseline but only 17 (49%) from the previous assessment. Regression analysis of results from the pre-biological era estimated that as much as 0.6 of the 1.8 apparent DAS response to TNF-a inhibitors might be accounted for by RTM. Conclusions. Assessing change in DAS from commencement of biological therapy may overestimate response, due to the impact of RTM and fluctuation in disease. Adequacy of response might be better assessed by serial assessments and a wider range of patient-centred outcomes.