Vectra® Measures 12 Biomarkers Implicated in Key Pathways of Rheumatoid Arthritis

The 12 Biomarkers included in the Vectra score provide a molecular measure of inflammation

VCAM-1 Vascular Cell Adhesion Molecule-1 VCAM-1

(Vascular cell adhesion molecule-1) is an adhesion molecule expressed by endothelial and synovial cells. VCAM-1 may contribute to cellular recruitment to synovial tissue, as well as to cartilage invasion and destruction by fibroblasts. Vectra measures the soluble form of VCAM-1.

IL-6 Interleukin 6

IL-6 (Interleukin 6) is a cytokine produced by multiple cells, including leukocytes, fibroblasts, and skeletal cells in RA. IL-6 is a major driver of RA inflammation, cartilage degradation, bone erosion, and the hepatic acute phase response.

MMP-3 Matrix Metalloproteinase-3 or Stromelysin-1

MMP-3 (Matrix metalloproteinase-3 or stromelysin-1) is an enzyme that degrades glycosaminoglycan components to cartilage and also activates the collagenase MMP-1.


Resistin is also a hormone associated with the adipose tissue. Like leptin, it can be secreted by synovial tissue and bone and promotes inflammation and bone remodeling. Resistin has been associated with obesity and diabetes.

EGF Epidermal Growth Factor

EGF (Epidermal growth factor) is a growth factor secreted by macrophages, fibroblasts, and endothelial cells in RA joint tissue. EGF is associated with proliferation and differentiation of stromal cells (fibroblasts, chondrocytes, endothelial cells) and can induce production of inflammatory mediators and proteinases in these cells. EGF may also modulate the hepatic acute phase response.

TNF-RI Tumor Necrosis Factor Receptor, Type 1

TNF-RI (Tumor necrosis factor receptor, type 1) is a receptor for TNF-a that is expressed on the membranes of numerous cell types. TNF-R1 mediated signaling contributes to multiple effects of TNF-a including induction of cell death. Vectra measures the soluble form, TNF-R1, which binds to and neutralizes TNF-a.

YKL-40 Human Cartilage Glycoprotein 39

YKL-40, or human cartilage glycoprotein 39, is secreted primarily by chondrocytes and differentiated macrophages. YKL-40 may promote chondrocyte and fibroblast proliferation and antagonize cartilage destruction. YKL-40 reactive T cells have been found in RA patients, suggesting that it may contribute to RA autoimmunity.

SAA Serum Amyloid

SAA (Serum amyloid) is another major acute phase protein secreted by the liver in response to inflammation. Like CRP, elevated SSA may be associated with cardiovascular risk. SAA may also be produced by synovial fibroblasts and chondrocytes, and may induce proinflammatory activation of fibrobasts, macrophages, and T cells.

VEGF-A Vascular Endothelial Growth Factor A

VEGF-A (Vascular endothelial growth factor A) is a potent angiogenic growth factor and vascular permeability factor expressed by various synovial cells including fibroblasts and macrophages. VEGF-A promotes inflammation, fluid accumulation, and bone erosion.

MMP-1 Matrix Metalloproteinase-1 or Collagenase-1

MMP-1 (Matrix metalloproteinase-1 or collagenase-1) is a collagen-degrading enzyme that contributes to cartilage destruction in RA and to leukocyte invasion and angiogenesis in the synovial tissue.


Leptin is a hormone secreted by adipose tissue, synovial tissue and bone. A satiety factor associated with obesity, leptin can also activate leukocytes and regulate bone remodeling.

CrP C-Reactive Protein

CRP (C-reactive protein) is a major acute phase protein secreted by the liver in response to inflammation. Elevated CRP levels are associated with an elevated risk of cardiovascular disease.

Vectra® Technical Specifications
Crescendo Biosciences, Inc. Effective Date: May, 2019


Indications and Use

Intended Use
Vectra® is a multi-biomarker blood test for measuring rheumatoid arthritis (RA) inflammatory disease activity. It is validated for use in adults diagnosed with RA. Vectra measures the serum concentrations of 12 protein biomarkers reflecting the pathobiology of RA and combines them with demographic and clinical information (age, gender and adiposity) to generate an integer score on a scale of 1 to 100 that represents the level of RA disease activity in that patient.

Summary and Explanation
The Vectra test measures the following 12 biomarkers: adhesion molecules (vascular cell adhesion molecule 1 [VCAM-1]); growth factors (epidermal growth factor [EGF] and vascular endothelial growth factor A [VEGFA]); cytokine-related proteins (interleukin 6 [IL-6] and tumor necrosis factor receptor type I [TNFRI]); matrix metalloproteinases (matrix metalloproteinase 1 and 3 [MMP-1]; [MMP-3]); a skeletal-related protein (cartilage glycoprotein 39 [YKL-40]); hormones (leptin and resistin); and acute-phase proteins (serum amyloid A [SAA] and C-reactive protein [CRP]). The concentrations of these 12 biomarkers are measured in serum and entered in a proprietary formula to generate a score on a scale of 1 to 100 that represents the level of RA disease activity. By design, the formula is the sum of terms that are biomarker-based predictions of the 28-joint tender joint count (TJC28), 28-joint swollen joint count (SJC28) and patient global assessment, each of which uses many of the 11 non-CRP Vectra biomarkers, and a CRP term. Together, they form an biomarker-based equation analogous to the formula of the Disease Activity Score in 28 joints (DAS28-CRP). DAS28 (with ESR or CRP) is the most widely accepted tool for assessing disease activity in adults with RA in clinical trials.


Vectra® was validated to assess RA disease activity through a rigorous development process.

The 12 protein biomarkers were selected from a pool of 396 candidate biomarkers
  • Validated against the DAS28-CRP in both seropositive (AUROC = 0.77; P<0.001) and seronegative patients (AUROC = 0.70; P<0.001)
  • Significantly correlated with change in disease activity based on DAS28-CRP and DAS28-ESR
  • Precise and reproducible — 28 samples were each assayed 10 times over multiple days with multiple operators (median coefficient of variation = 1.6%)
Crescendo Bioscience Laboratory Certifications

Federal CLIA Certificate
The Centers for Medicare & Medicaid Services (CMS) regulate all laboratory testing performed on humans in the U.S. through the Clinical Laboratory Improvement Amendments (CLIA). The objective of the CLIA program is to ensure quality laboratory testing.

CAP Laboratory Accreditation Program
The commission on Laboratory Accreditation of the College of American Pathologists examined Crescendo Bioscience’s laboratory records and quality control procedures for the preceding 2 years. In addition, staff qualifications, laboratory equipment, and the facility’s safety program and record, as well as the overall lab management were examined.

New York State Clinical Laboratory Permit
The Wadsworth Center at the New York Department of Health through its Clinical Laboratory Evaluation Program (CLEP) issued a laboratory permit to Crescendo Bioscience to provide services to physicians/patients in New York. The excellence of the CLEP program has been acknowledged by CMS through their granting of exempt status from the federal CLIA for laboratories located in and holding NYS clinical laboratory permits.

CMS coverage policy issued by Palmetto GBA for Vectra
Palmetto GBA posted a favorable coverage article for Vectra on May 10, 2013 under the Medicare Part B program, which also drives coverage policies for the large Medicare Advantage Plans.

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