Validation of the 28-joint Disease Activity Score (DAS28) and European League Against Rheumatism response criteria based on C-reactive protein against disease progression in patients with rheumatoid arthritis, and comparison with the DAS28 based on erythrocyte sedimentation rate

Abstract

Objective: To validate and compare the definition of the Disease Activity Score 28 based on C-reactive protein (DAS28 (CRP)) to the definition based on erythrocyte sedimentation rate (ESR).

Methods: Data were analysed from two randomised, double-blind, placebo-controlled trials of abatacept of 6-month and 12-month duration in patients with rheumatoid arthritis. European League Against Rheumatism (EULAR) response criteria and the proportion of patients in remission (DAS28 <2.6) based on the two DAS28 definitions were examined. Trends in radiographic progression (erosion score, joint space narrowing score and total score) and physical function (Health Assessment Questionnaire Disability Index (HAQ-DI)) across the EULAR responder states (none, moderate and good) were analysed.

Results: There was general agreement in determining the EULAR responder state using both DAS28 definitions (kappa = 0.80, 95% CI 0.76 to 0.83). Overall, there was 82.4% agreement on the EULAR response criteria; when disagreements occurred, the DAS28 (CRP) yielded a better EULAR response more often then DAS28 (ESR) (12.6% vs 4.9%, respectively). There was also agreement in determining remission: kappa = 0.69 (95% CI 0.60 to 0.78). Radiographic progression decreased in patients treated with abatacept across EULAR states (from none to moderate to good) based on both definitions. For patients treated with placebo, the trend was not as pronounced, with radiographic scores higher for moderate vs non-responders. For physical function, similar trends were observed across the EULAR states for both DAS28 definitions.

Conclusions: The DAS28 (CRP) has been validated against radiographic progression and physical function. While the DAS28 (CRP) yielded a better EULAR response more often than the DAS28 (ESR), the validation profile was similar to the DAS28 (ESR), indicating that both measures are useful for assessing disease activity in patients with rheumatoid arthritis.

Figure 1

Bland–Altman plot of 28-joint Disease Activity Score (DAS28) C-reactive protein (CRP) and DAS28 erythrocyte sedimentation rate (ESR) values for patients in the ATTAIN (Abatacept Trial in Treatment of Anti-TNF INadequate responders) and AIM (Abatacept in Inadequate responders to Methotrexate) trials (both treatment groups) at 6 months. Difference between DAS28 (ESR) and DAS28 (CRP) scores vs mean value of DAS28 (ESR) and DAS28 (CRP) score combined for patients in the ATTAIN and AIM trials (both treatment groups) at 6 months. The central line represents the mean difference between the two measures, and the upper and lower bounds represent 2SD from the mean.

Figure 2

Improvements in physical function across European League Against Rheumatism (EULAR) states based on 28-joint Disease Activity Score (DAS28) C-reactive protein (CRP) and DAS28 erythrocyte sedimentation rate (ESR) for patients in the ATTAIN (Abatacept Trial in Treatment of Anti-TNF INadequate responders) and AIM (Abatacept in Inadequate responders to Methotrexate) trials (both treatment groups). Mean improvement from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI), for combined abatacept and patients treated with placebo who were EULAR good, moderate or non-responders based on DAS28 (CRP) or DAS28 (ESR). A. Mean improvement from baseline to 6 months for patients in the ATTAIN trial. B. Mean improvement from baseline to 6 months for patients in the AIM trial. Error bars represent the standard error of the mean (SEM).