Validation of a novel multibiomarker test to assess rheumatoid arthritis disease activity

Abstract

Objective Quantitative assessment of disease activity in rheumatoid arthritis (RA) is important for patient management, and additional objective information may aid rheumatologists in clinical decision-making. We validated a recently-developed multi-biomarker disease activity (MBDA) test relative to clinical disease activity in diverse RA cohorts. Methods Serum samples were obtained from the InFoRM, BRASS, and Leiden Early Arthritis Clinic cohorts. Levels of 12 biomarkers were measured and combined according to a pre-specified algorithm to generate the composite MBDA score. The relationship of the MBDA score to clinical disease activity was characterized separately in seropositive and seronegative patients using Pearson correlations and area under the receiver operator characteristic curve (AUROC) to discriminate between patients with low and moderate/high disease activity. Associations between changes in MBDA score and clinical responses 6–12 weeks after initiation of anti-TNF or methotrexate treatment were evaluated by AUROC. Results The MBDA score was significantly associated with DAS28-CRP in both seropositive (AUROC=0.77; P<0.001) and seronegative patients (AUROC=0.70; P<0.001). In subgroups based on age, sex, body-mass index, and treatment, the MBDA score was associated with DAS28-CRP (P<0.05) in all seropositive and most seronegative subgroups. Changes in MBDA score at 6–12 weeks could discriminate both ACR50 responses (P=0.03) and DAS28-CRP improvement (P=0.002). Changes in MBDA score at 2 weeks were also associated with subsequent DAS28-CRP response (P=0.02). Conclusion Our findings establish the criterion and discriminant validity of a novel multi-biomarker test as an objective measure of RA disease activity to aid in the management of RA patients.

A Multibiomarker Disease Activity Score for Rheumatoid Arthritis Predicts Radiographic Joint Damage in the BeSt Study

“…The MBDA algorithm (Vectra DA algorithm score) has been validated and described previously 4,9,10 . The MBDA score is calculated by an algorithm in which levels of 12 biomarkers, mentioned in the previous paragraph, are entered.…”

Reanalysis of the Multi‐Biomarker Disease Activity Score for Assessing Disease Activity in the Abatacept Versus Adalimumab Comparison in Biologic‐Naive Rheumatoid Arthritis Subjects with Background Methotrexate Study: Comment on the Article by Fleischmann et al

“…Second, the MBDA score was initially developed to correlate with the DAS28-CRP, and its RA disease activity categories were established using cutoffs that are specific to the DAS28-CRP (14). Thresholds for DAS28-CRP RA disease activity categories are systematically lower than the corresponding cutoffs in the DAS28 using the erythrocyte sedimentation rate (ESR) (15,16), as noted in the editorial accompanying Fleischmann and colleagues' article (17).…”

“…For both the DAS28-CRP and the other clinical measures examined (e.g., CDAI, SDAI), the claim of no clear association between MBDA scores and commonly used, validated clinical measures was not supported by a statistical test of no association that cross-classified the MBDA category of each patient with his or her clinically defined RA disease activity category. 863 Regardless, because the MBDA score was designed to complement, not supplant, clinical assessment, some discordance between clinical and laboratory-based assessments is not only expected (14,18,19), but desirable. Otherwise, the laboratory test would contain no incremental information beyond that offered by clinical evaluation.…”

Reliable and cost-effective serodiagnosis of rheumatoid arthritis

“…Multiple biomarkers of disease activity in RA have been evaluated in studies originating from both Africa [6][7][8][9][10][11] and elsewhere [12][13][14][15][16]. In addition, commercial ventures have also focused on developing multi-array test profiles that may improve cost-effective management of RA [15,17].…”