Development and Validation of Modified Disease Activity Scores in Rheumatoid Arthritis: Superior Correlation With Magnetic Resonance Imaging–Detected Synovitis and Radiographic Progression

Abstract

To develop and validate composite disease activity scores, based on widely available clinical measures, that would demonstrate improved correlation with detection of synovitis on magnetic resonance imaging (MRI) and radiographic progression, in comparison with conventional measures, in patients with rheumatoid arthritis (RA). This study was conducted as a secondary study of 2 RA clinical trials, GO-BEFORE (development cohort) and GO-FORWARD (validation cohort). Generalized estimating equations were used to evaluate independent cross-sectional associations of component variables (from all time points) with concurrent MRI measures of synovitis and bone edema in the development cohort. Based on regression coefficients, modified versions of the Disease Activity Score in 28 joints (M-DAS28), Simplified Disease Activity Index (M-SDAI), and Clinical Disease Activity Index (M-CDAI) were generated for each subject in the validation cohort. The M-DAS28, M-SDAI, and M-CDAI scores were compared to conventional scores of disease activity with regard to associations with MRI measures of synovitis and radiographic progression, assessed using Pearson's and Spearman's correlations, linear/logistic regression, and receiver operating characteristic analysis. Four variables were independently associated with MRI-detected synovitis and bone edema in the development cohort: C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), swollen joint count in 28 joints (SJC28), and evaluator's global assessment of disease activity using a visual analog scale (EvGA score). Modified disease activity scores were generated using the regression coefficients obtained in the synovitis models for all subjects in the validation cohort; modified scores were calculated as M-DAS28 = 0.49 × ln(CRP) + 0.15 × SJC28 + 0.22 × EvGA + 1 and M-SDAI = CRP + SJC28 + EvGA. Both modified and conventional disease activity scores correlated significantly with MRI measures of synovitis. Modified scores showed superior correlation with synovitis, as compared to conventional scores, at all time points (P < 0.05). Furthermore, the M-DAS28 and M-SDAI had superior test characteristics for prediction of radiographic progression at 52 weeks (both P < 0.05). Modified disease activity scores demonstrated superior correlation with MRI detection of synovitis at all time points, and more accurately predicted radiographic progression in patients with RA in a clinical trial setting.