Vectra DA Dx

Synonyms: MBDA (multibiomarker disease activity) test

CPT Code: 84999, 81479, 83520

Definition: Vectra DA is a multibiomarker based assay designed to correlate with disease activity in rheumatoid arthritis (RA).

Description: Vectra DA measures 12 serum inflammatory and disease activity biomarkers and reports a composite score ranging from 0-100.  The choice of its 12 analytes and weighting was based on correlations with validated outcome and activity measures from analyses of RA patients. Results from Vectra DA tests have also been has been correlated with various outcomes in clinical trials. There is some evidence attesting to its utility as an adjunctive measure of clinical activity.  However, it has not been shown to be superior to the clinical exam and physician acumen.

Method: MBDA is performed on serum as a multiplex sandwich electrochemiluminescent immunoassay using biomarker specific capture antibodies. During the development, 130 candidate biomarkers were reduced to 12 based on their association with multiple clinical measures (e.g., DAS28-CRP, etc.). MBDA measures EGF, VEGF-A, leptin, resistin, IL-6, SAA, CRP, VCAM-1, MMP-1, MMP-3, TNF-R1, and YKL-40.  Currently, assays are performed  only in single a California lab and results are reported within 7-10 days of receipt.

Normal Values; Normal values are less than 25.  Values range from 0-100 and reports show MDA values as correlated with disease activity, DAS28-CRP, and DAS28-ESR levels.

Abnormal Values:  low activity=25-29 ;  moderate activity=30-44; high activity >44.

Clinical Associations:  In multiple cohorts (clinic cohorts, clinical trial serum samples) the MBDA has been shown to correlate moderately well with the DAS-CRP, SDAI, CDAI and RAPID3 with correlation coefficients ranging from 0.21 to 0.29 in seronegative RA and 0.43 to 0.56 in rheumatoid factor (RF) positive RA patients.

Limitations:  Vectra has not been studied in disorders other than RA and should not be employed in other inflammatory arthropathies or in juvenile idiopathic arthritis. MBDA is only available in the USA. Results are not reliable in patients treated with IL-6 targeting therapies such as tocilizumab, because such therapies increase detected serum levels of IL-6 (bound to antibody) and spuriously elevate the results. It has not been fully delineated how the Vectra test varies and thus, how it should be interpreted in RA patients with intercurrent conditions that may also affect the serum levels of its analytes (e.g. infection, neoplasia).

Confounding Factors:  MBDA is unaffected by other comorbid diseases or the presence of RF or other autoantibodies.  There is no appreciable interference by hemolysis, icterus or hyperlipidemia.

Indications: Vectra is not a test for the diagnosis or for the selection of treatment in RA.  It has been marketed as a test to assess RA activity in adults and to guide physician management decisions in conjunction with standard clinical evaluations for RA.  Its’ characteristics and body of evidence suggests utility as an investigational tool in both clinical trials and pathophysiologic studies of RA.  Although the test is considered investigational by some insurers, Vectra has been approved by Medicare. Medicare covers Vectra DA with no copayment, however Medicare Advantage plans may require a copay.  To date, roughly 10% of US rheumatologists have used this test in the care of their RA patients.

Alternatives: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), IgM rheumatoid factor (RF) and cyclic citrullinated peptide (CCP) antibodies, 14-3-3η (Ident-RA) have variable strengths as biomarkers for RA.  Their use in disorders other than RA is less certain or unstudied.

Cost:  Vectra is a comparatively expensive assay with the cost depending on the payer and region. The cost ranges from ~$250 (contracted price) to ~$950 (list price). There is a patient assistance resource at  1-877-743-8639.

Comment:  Vectra is one of several available biomarkers with the potential of staging or assessing RA.  There is insufficient evidence that this MBDA provides a consistent incremental value over other clinical judgment or existing biomarkers (CRP, ESR, RF, and ACPA).  The quest for  an “ideal” biomarker has been frustrated by suboptimal sensitivity, specificity and likelihood ratios showing correlations with both disease activity and response to therapy. The ideal biomarker must have strong prognostic value, be technically feasible, have reproducible clinical validity and utility and high positive and negative predictive values such that it and correlations with high risk and poor outcome states. The Vectra test has not yet been tested in a prospective clinical trial wherein clinical decision based on Vectra values are compared to current standards (e.g., DAS28 or CRP) to optimize both short term (activity or response) and long term (Xray or need for surgery) outcomes.

BIBLIOGRAPHY

Curtis JR, van der Helm van Mil AH, Knevel R, et al. Validation of a novel multibiomarker test to assess rheumatoid arthritis disease activity.  Arthritis Care Res 2012; 64: 1794-1803  PMID:22736476