BlueCross BlueShield of Tennessee Medical Policy Manual

Multi-biomarker Testing for Rheumatoid Arthritis


A potential approach to assessment of disease activity for rheumatoid arthritis (RA) is the use of a multi biomarker disease activity (MBDA) scores (e.g. Vectra® DA). Commercially available MBDA blood test that use 12 serum biomarkers to construct a disease activity score ranging from 0 (low) to 100 (high) to predict disease progression are currently being investigated.

Assessment of disease activity in rheumatoid arthritis (RA) is an important component of treatment management, as one of the main goals of treatment is to maintain a state of low disease activity and/or remission. There are a variety of available instruments for measuring RA disease activity. The most widely used and validated in clinical research is the Disease Activity Score (DAS) 28 score; a composite measure that includes examination of 28 joints for swelling and tenderness, combined with patient reported symptoms and measurement of C-reactive protein or erythrocyte sedimentation rate. The DAS 28 along with 5 other disease activity measurement tools (Clinical Disease Activity Index, Patient Activity Scale, Patient Activity Scale II, Routine Assessment of Patient Index, and the Simplified Disease Activity Index) are endorsed by the American College of Rheumatology (ACR) as the most useful and feasible tools for point-of-care assessment.

NOTE: The policy statement only applies to the panel tests performed in determining a multi-biomarker disease score and is not relevant to any of these tests when performed alone (i.e., not part of a panel test).




Vectra® DA has been compared to standard disease activity in simulated cases and physician survey.  There are no randomized controlled trials that compare use of the multi-biomarker score to an ACR endorsed alternative method of measuring disease activity, and as a result there is no direct evidence that MBDA scores improve outcomes.  There is insufficient evidence to determine whether MBDA is as good as other more established disease activity measures (e.g. DAS 28) in improving outcomes.


American College of Rheumatology (2015) Guideline for the treatment of rheumatoid arthritis. Retrieved October 17, 2016 from

BlueCross BlueShield Association. Medical Policy Reference Manual. (6:2018). Multibiomarker disease activity blood test for rheumatoid arthritis (2.04.119). Retrieved September 4, 2018 from BlueWeb. (24 articles and/or guidelines reviewed)

Hambardzumyan, K., Bolce, R., Saevarsdottir, S., Cruickshank, S., Sasso, E., Chernoff, D., et al. (2014). Pretreatment multi-biomarker disease activity score and radiographic progression in early RA: results from the SWEFOT trial. Annals of Rheumatic Diseases, doi: 10.1136/annrheumdis-2013-204986. (Level 4 evidence)

Hambardzumyan, K., Bolce, R., Saevarsdottir, S., Forslind, K., Wallman, J., Cruickshank, S., et. al. (2016) Association of a multibiomarker disease activity score at multiple time-points with radiographic progression in rheumatoid arthritis: results from the SWEFOT trial. Rheumatic & Musculoskeletal Diseases. 2016, e000197. Doi: 10.1136/rmdopen-2015-000197. (Level 4 evidence)

Hirata, S., Dirven, L., Shen, Y., Centola, M., Cavet, G., Lems, W., et al. (2013). A multi-biomarker score measures rheumatoid arthritis disease activity in the BeST study. Rheumatology, 52 (7), 1202-1207.

Li, W., Sasso, E., van der Helm-van Mil, A., and Huizinga, T. (2015, September) Relationship of multi-biomarker disease activity score and other risk factors with radiographic progression in an observational study of patients with rheumatoid arthritis. Rheumatology 2016, 55, 357-366. (Level 4 evidence)

Markusse, I., Dirven, L., van den Broek, M., Bijkerk, C., Han, K., Ronday, H., et. al., (2014) A multibiomarker disease activity score for rheumatoid arthritis predicts radiographic joint damage in the BeSt study. The Journal of Rheumatology 2014, 41 (11), 2114-2119. (Level 4 evidence)

Palmetto GBA. (2017). Vectra DA coding and billing guidelines (M00031, V10). Retrieved October 17, 2017 from

Rech, J., Hueber, A., Finzel, S., Englbrecht, M. Haschka, J., Manger, B. et al. (2015). Prediction of disease relapses by multibiomarker disease activity and autoantibody status in patients with rheumatoid arthritis on tapering DMARD treatment. Annals of Rheumatic Disease, 2016, 75, 1637–1644. (Level 4 evidence)

Segurado, O., & Sasso, E. (2014). Vectra DA for the objective measurement of disease activity in patients with rheumatoid arthritis. Clinical and Experimental Rheumatology, 32 (5, Suppl 85), S-29-34. Abstract retrieved October 17, 2017 from PubMed database.

Winifred S. Hayes, Inc. Medical Technology Directory. (2018, January). Vectra DA test (Crescendo Bioscience Inc.) for management of patients with rheumatoid arthritis. Retrieved September 4, 2018 from (39 articles and/or guidelines reviewed)




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