Characterization of a multiplex, 12-biomarker test for rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disorder that primarily involves the joints. Accurate and frequent assessment of RA disease activity is critical to optimal treatment planning. A novel algorithm has been developed to determine a multi-biomarker disease activity (MBDA) score based upon measurement of the concentrations of 12 serum biomarkers in multiplex format. Biomarker assays from several different platforms were used in feasibility studies to identify biomarkers of potential significance. These assays were adapted to a multiplex platform for training and validation of the algorithm. In this study, the analytical performance of the underlying biomarker assays and the MBDA score was evaluated. Quantification of 12 biomarkers was performed with multiplexed sandwich immunoassays in three panels. Biomarker-specific capture antibodies were bound to specific locations in each well; detection antibodies were labeled with electrochemiluminescent tags. Data were acquired with a Sector Imager 6000, and analyte concentrations were determined. Parallelism, dynamic range, cross-reactivity, and precision were established for each biomarker as well as for the MBDA score. Interference by serum proteins, heterophilic antibodies, and common RA therapies was also assessed. The individual biomarker assays had 3-4 orders of magnitude dynamic ranges, with good reproducibility across time, operators, and reagent lots; the MBDA score had a median coefficient of variation of <2% across the score range. Cross-reactivity as well as interference by serum rheumatoid factor (RF), human anti-mouse antibodies (HAMA), or common RA therapies, including disease-modifying antirheumatic drugs and biologics, was minimal. The same MBDA score was observed in different subjects despite having different biomarker profiles, supporting prior literature reports that multiple pathways contribute to RA.

A multianalyte PCR blood test outperforms single analyte ELISAs (chromogranin A, pancreastatin, neurokinin A) for neuroendocrine tumor detection

“…Algorithmic analyses, using the results of these assays as well as other patient information (if used), can then be performed and are typically reported as a numeric score(s) or as a probability (Eastman et al 2012) that can provide additional prognostic and predictive information, further aiding clinical management (Cornejo et al 2014). The strengths of MAAAs are the incorporation of multiple informative data points as well as these are typically undertaken by a single dedicated facility (Lee & Hall 2009).…”

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

“…We would encourage readers to make the distinction between the scientific validity of a diagnostic test and its clinical utility. There is already a sizable evidence base supporting the development and validation of the MBDA test in diverse RA patient cohorts (9)(10)(11)(12)(13)(18)(19)(20)(23)(24)(25). A prospective clinical trial is underway to rigorously evaluate its clinical utility and its potential role in RA patient management (26).…”