Pretreatment multi-biomarker disease activity score and radiographic progression in early RA: results from the SWEFOT trial

Abstract

Objectives: Prediction of radiographic progression (RP) in early rheumatoid arthritis (eRA) would be very useful for optimal choice among available therapies. We evaluated a multi-biomarker disease activity (MBDA) score, based on 12 serum biomarkers as a baseline predictor for 1-year RP in eRA.

Methods: Baseline disease activity score based on erythrocyte sedimentation rate (DAS28-ESR), disease activity score based on C-reactive protein (DAS28-CRP), CRP, MBDA scores and DAS28-ESR at 3 months were analysed for 235 patients with eRA from the Swedish Farmacotherapy (SWEFOT) clinical trial. RP was defined as an increase in the Van der Heijde-modified Sharp score by more than five points over 1 year. Associations between baseline disease activity measures, the MBDA score, and 1-year RP were evaluated using univariate and multivariate logistic regression, adjusted for potential confounders.

Results: Among 235 patients with eRA, 5 had low and 29 moderate MBDA scores at baseline. None of the former and only one of the latter group (3.4%) had RP during 1 year, while the proportion of patients with RP among those with high MBDA score was 20.9% (p=0.021). Among patients with low/moderate CRP, moderate DAS28-CRP or moderate DAS28-ESR at baseline, progression occurred in 14%, 15%, 14% and 15%, respectively. MBDA score was an independent predictor of RP as a continuous (OR=1.05, 95% CI 1.02 to 1.08) and dichotomised variable (high versus low/moderate, OR=3.86, 95% CI 1.04 to 14.26).

Conclusions: In patients with eRA, the MBDA score at baseline was a strong independent predictor of 1-year RP. These results suggest that when choosing initial treatment in eRA the MBDA test may be clinically useful to identify a subgroup of patients at low risk of RP.

Trial registration number: WHO database at the Karolinska Institute: CT20080004; and clinicaltrials.gov: NCT00764725.

Keywords: Anti-TNF; Cytokines; Disease Activity; Patient perspective; Rheumatoid Arthritis.

Figure 1

Probability plots of radiographic progression at year 1 for high, moderate and low disease activity patient (N=235) grouped according to baseline MBDA (A), CRP (B), DAS28 (C) and ESR (D). Each black circle represents a patient with low disease activity, red triangle—moderate disease activity and blue square—high disease activity. Horizontal dashed line represents ΔSHS=5 from baseline to 1 year, above which the change is considered as rapid radiographic progression (ΔSHS>5). DAS28, disease activity score; ESR, erythrocyte sedimentation rate; MBDA, multi-biomarker disease activity; SHS, Sharp–van der Heijde score.

Figure 2

Cross tabulation of all analysed patients (N=235) and subset (n=43) with rapid radiographic progression (ΔSHS>5) over 1  year, by baseline disease activity measures. The denominator in each cell represents the number of patients cross classified by baseline MBDA score and DAS28-ESR (A), baseline MBDA score and DAS28-CRP (B) and baseline MBDA score and CRP (C) disease activity scores. The numerator in each cell represents the number of patients with radiographic progression at 1 year. (D) Radiographic progression for MBDA low, moderate and high score groups (%). Radiographic progression at 1 year is defined by increase in SHS>5 compared with baseline. CRP, C-reactive protein; DAS28-CRP, disease activity score based on C-reactive protein; DAS28-ESR, disease activity score based on erythrocyte sedimentation rate; MBDA, multi-biomarker disease activity; SHS, Sharp–van der Heijde score.