Abstract
BackgroundThe multi-biomarker disease activity (MBDA) test measures 12 serum protein biomarkers to quantify disease activity in RA patients. A newer version of the MBDA score, adjusted for age, sex, and adiposity, has been validated in two cohorts (OPERA and BRASS) for predicting risk for radiographic progression. We now extend these findings with additional cohorts to further validate the adjusted MBDA score as a predictor of radiographic progression risk and compare its performance with that of other risk factors.MethodsFour cohorts were analyzed: the BRASS and Leiden registries and the OPERA and SWEFOT studies (total N = 953). Treatments included conventional DMARDs and anti-TNFs. Associations of radiographic progression (ΔTSS) per year with the adjusted MBDA score, seropositivity, and clinical measures were evaluated using linear and logistic regression. The adjusted MBDA score was (1) validated in Leiden and SWEFOT, (2) compared with other measures in all four cohorts, and (3) used to generate curves for predicting risk of radiographic progression.ResultsUnivariable and bivariable analyses validated the adjusted MBDA score and found it to be the strongest, independent predicator of radiographic progression (ΔTSS > 5) compared with seropositivity (rheumatoid factor and/or anti-CCP), baseline TSS, DAS28-CRP, CRP SJC, or CDAI. Neither DAS28-CRP, CDAI, SJC, nor CRP added significant information to the adjusted MBDA score as a predictor, and the frequency of radiographic progression agreed with the adjusted MBDA score when it was discordant with these measures. The rate of progression (ΔTSS > 5) increased from < 2% in the low (1–29) adjusted MBDA category to 16% in the high (45–100) category. A modeled risk curve indicated that risk increased continuously, exceeding 40% for the highest adjusted MBDA scores.ConclusionThe adjusted MBDA score was validated as an RA disease activity measure that is prognostic for radiographic progression. The adjusted MBDA score was a stronger predictor of radiographic progression than conventional risk factors, including seropositivity, and its prognostic ability was not significantly improved by the addition of DAS28-CRP, CRP, SJC, or CDAI.
Highlights
The goals of managing patients with rheumatoid arthritis (RA) are to minimize inflammation, joint damage, and disability
The adjusted multi-biomarker disease activity (MBDA) score was validated as an RA disease activity measure that is prognostic for radiographic progression
The adjusted MBDA score was a stronger predictor of radiographic progression than conventional risk factors, including seropositivity, and its prognostic ability was not significantly improved by the addition of DAS28-Creactive protein (CRP), CRP, Swollen joint count (SJC), or Clinical Disease Activity Index (CDAI)
Summary
The goals of managing patients with rheumatoid arthritis (RA) are to minimize inflammation, joint damage, and disability. To achieve these goals, RA disease activity should be quantitatively assessed on a regular basis, with treatment adjusted as needed to achieve remission or the lowest possible level of disease activity [1, 2]. RA disease activity should be quantitatively assessed on a regular basis, with treatment adjusted as needed to achieve remission or the lowest possible level of disease activity [1, 2] This strategy should be initiated from disease onset because the disability associated with joint damage is irreversible. We extend these findings with additional cohorts to further validate the adjusted MBDA score as a predictor of radiographic progression risk and compare its performance with that of other risk factors
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