Development and validation of a new disease activity score in 28 joints-based treatment response criterion for rheumatoid arthritis

Objective To define a valid criterion for treatment response as assessed by the Disease Activity Score in 28 joints (DAS28) that exceeds random disease activity variations in patients with rheumatoid arthritis (RA). Methods We utilized anonymized data sets of RA patients from multiple rheumatology centers in Germany to identify patients with stable responses to conventional or biologic disease-modifying antirheumatic drug (DMARD) therapy (discovery cohort). To evaluate fluctuations in DAS28 scores, we subjected patients' DAS28 scores at months 12, 18, and 24 to an analysis of variance model to establish a 1-sided 95% confidence interval for normal fluctuations; this value was used to define the critical difference (DAS28-dcrit) for individual changes from baseline. The DAS28-dcrit value was then applied to analyses of therapeutic response in an adalimumab noninterventional study cohort. Results The discovery cohort included 415 patients receiving stable treatment. Values for DAS28-dcrit were comparable regardless of age, sex, disease activity, and class of therapy (DMARDs or biologic agents) and fell below 1.8 in all subgroups. We therefore conclude that DAS28 improvements of 1.8 or higher are outside the normal variation and represent a therapeutic response. When applied to data from the adalimumab noninterventional study (n = 1,874), a DAS28-dcrit response was more robust over time than a European League Against Rheumatism response and was more closely correlated with improved functional capacity. Conclusion Based on our data, a DAS28-dcrit value of 1.8 signifies a positive individual therapeutic response that exceeds the threshold of random fluctuation. The DAS28-dcrit criterion may be useful in steering individual therapy and stratifying clinical trials.