Development and Validation of a New Disease Activity Score in 28 Joints–Based Treatment Response Criterion for Rheumatoid Arthritis

Abstract

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-d crit ) for individual changes from baseline. The DAS28-d crit value was then applied to analyses of therapeutic response in an adalimumab noninterventional study cohort.

Sustained effectiveness and safety of subcutaneous tocilizumab over two years in the ARATA observational study

“…Assessments of individual therapeutic responses found that 64% of patients had a DAS28-d crit response, defined as a DAS28-ESR reduction of ≥1.8 from baseline, at week 104. DAS28-dcrit responses were sustained for a median of slightly less than 1 year, consistent with other reports documenting the stability of DAS28-d crit responses (16,26). Time-to-event and Kaplan-Meier analyses did not identify any significant associations between baseline characteristics and DAS28-d crit responses.…”

Association of Improvement in Pain With Therapeutic Response as Determined by Individual Improvement Criteria in Patients With Rheumatoid Arthritis

“…As reported previously 4, this measure of response is clearly distinguishable from random variations in disease activity and is robust over time. Approximately three‐fourths of patients with a DAS28 response had a significant improvement in pain, function, or fatigue, and more than 20% had a response in all 3 PROs, indicating that therapeutic responses as assessed by the DAS28‐d crit are associated with improvements in PROs in the majority of patients.…”

“…The key role played by pain was further revealed in our analyses of significant individual PRO responses occurring in patients with a therapeutic response at month 12 as assessed by DAS28‐d crit (improvement from baseline of at least 1.8 points) 4. More than two‐thirds of patients with a DAS28 response also reported a significant improvement in pain, either alone or in combination with another PRO.…”

“…For pain and fatigue, both of which were measured on scales ranging from 0 to 10, a decrease of 3 and 4 points, respectively, was required for a statistically significant improvement. For function, which was measured by the FFbH questionnaire on a scale ranging from 0 to 100, a change of 16 points was required; this was slightly lower than the d crit value of 18 points determined previously in a smaller cohort of patients 4. Accordingly, these measures required a change from baseline representing approximately 20% to 40% of the full measurement scale.…”

Measures of Rheumatoid Arthritis Disease Activity

“…With repeated testing one week apart, DAS28 correlations ranged from 0.79–0.87, with an ICC of 0.85 ( 9 , 16 ). Results were similar when retesting at 24 months in patients on stable therapy ( 46 ). The SDD for the DAS28 is 1.3 ( 16 ).…”