Objectives: Imaging of joint inflammation provides a standard against which to derive an updated disease activity score (DAS) for rheumatoid arthritis (RA). Our objectives were to develop and validate a DAS based on reweighting the DAS28 components to maximize association with ultrasound-assessed synovitis.
Methods: Early RA patients from two observational cohorts (n=434 & n=117), and a clinical trial (n=59) were assessed at intervals up to 104 weeks from baseline; all ultrasound scans were within 1 week of clinical exam. There were 899, 163 and 183 visits in each cohort. Associations of combined ultrasound grey scale and power Doppler scores (GSPD) with TJC28 & SJC28, CRP, ESR, general health visual analogue scale were examined in linear mixed model regressions. Cross-validation evaluated model predictive ability; coefficients learned from training data defined a re-weighted DAS28 which was validated against radiographic progression in independent data (3037 observations; 717 patients).
Results: Of the conventional DAS28 components only SJC28 and CRP were associated with GSPD in all three development cohorts. A 2-component model including SJC28 and CRP outperformed a 4-component model (R-squared 0.235, 0.392, 0.380 vs. 0.232, 0.380, 0.375 respectively). The re-weighted 2-component DAS28CRP outperformed conventional DAS28 definitions in predicting GSPD (Δtest log-likelihood<-2.6, p<0.01), Larsen score and presence of erosions.
Conclusion: A score based on SJC28 and CRP alone demonstrated stronger associations with synovitis and radiographic progression than the original DAS28 and should be considered in research on pathophysiological manifestations of early RA. Implications for clinical management of RA remain to be established.