Serum biomarker panel testing is proposed to inform the differential diagnosis of connective tissue diseases (CTDs) that share similar symptoms. Biomarkers are "chemicals" or proteins found in blood, urine or tissue that can indicate both normal and abnormal processes. Systemic lupus erythematosus (SLE) and other connective tissue diseases (e.g., rheumatoid arthritis, Grave’s disease, Hashimoto disease, Sjögren syndrome, antiphospholipid syndrome, polymyositis and dermatomyositis) can be difficult to diagnose because individuals often present with diverse, nonspecific symptoms that overlap. Currently, differential diagnosis depends on a combination of clinical signs and symptoms and individual laboratory tests. Recently, laboratory-developed, diagnostic panel tests with proprietary algorithms and/or index scores for the diagnosis of SLE and other CTDs have become commercially available.
There is one multi-biomarker test available proposed to aid in the diagnosis of SLE and other connective tissue diseases. This panel, Avise CTD (Exagen Diagnostics), contains 22 different tests. It combines two smaller panels, a 10-marker panel that incudes common SLE tests, as well as cell-bound complement activation products (known as Avise Lupus) and a 12-marker panel that focuses on CTDs other than SLE (known as Avise CTD). Avise CTD includes nuclear antigen antibodies markers to help distinguish CTD, a rheumatoid arthritis panel to rule-in or rule-out RA, an antiphospholipid syndrome panel to assess risk for thrombosis and cardiovascular events, and a thyroid panel to help rule-in or rule-out Grave’s disease and Hashimoto disease.
| 10-marker Avise Lupus Test | Auto-antibodies: ANA, anti-dsDNA, anti-mutated citrullinated vimentin, C4d erythrocyte-bound complement fragment, C4d lymphocyte-bound complement, anti-Sm, Jo-1, Sci-70, CENP, SS-B/La |
Avise CDT test |
Avise Lupus test plus the following: Auto-antibodies: U1RNP, RNP70, SS-A/Ro Rheumatoid arthritis auto-antibodies: rheumatoid factor IgM, rheumatoid factor IgA, anticyclic citrullinated peptide IgG Anti-phospholipid syndrome auto-antibodies: cardiolipin IgM, cardiolipin IgG, β2-glycoprotein 1 IgG, β2-glycoprotein 1 IgM Thyroid auto-antibodies: thyroglobulin IgG, thyroid, thyroid peroxidase |
POLICY
Serum biomarker panel testing with proprietary algorithms and/or index scores for the diagnosis of systemic lupus erythematosus and other connective tissue diseases is considered investigational.
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ADDITIONAL INFORMATION
No controlled studies were found in the published literature that validates the clinical utility of assessing multiple biomarkers simultaneously.
SOURCES
Agmon-Levin, N., Damoiseaux, J, Kallenberg, C., Sack, U., Witte, T., Herold, M., et al. (2014). International recommendations for the assessment of auto antibodies to cellular antigens referred to as anti-nuclear antibodies. Annals of the Rheumatic Diseases, 73 (1), 17-23. Abstract retrieved March 7, 2016 from PubMed database.
BlueCross BlueShield Association. Evidence Positioning System. (7:2023). Serum biomarker panel testing for systemic lupus erythematosus and other connective tissue diseases. (2.04.123). Retrieved October 27, 2023 from www.bcbsaoca.com/eps/. (14 articles and/or guidelines reviewed)
Dervieux, T., Conklin, J., Ligayon, J., Wolover, L., O'Malley, T., Alexander, R., et al. (2017). Validation of a multi-analyte panel with cell-bound complement activation products for systemic lupus erythematosus. Journal of Immunologic Methods, 446, 54-59. Abstract retrieved December 4, 2017 from PubMed database.
Liang, E., Taylor, M., & McMahon, M. (2020). Utility of the AVISE connective tissue disease test in predicting lupus diagnosis and progression. Lupus Science and Medicine, 18, 7 (1), e000345. (Level 3 evidence)
Mossell, J., Goldman, J., Barken, D., & Alexander, R. (2016). The Avise lupus test and cell-bound complement activation products aid the diagnosis of systemic lupus erythematosus. The Open Rheumatology Journal, 10, 71-80. (Level 4 evidence)
O’Malley, T., Xie, F., Su, Y., Clinton, C., Zack, D.J., Haechung, C., et al. (2022). Complement activation products vs standard ANA testing: Treatment outcomes, diagnosis, and economic impact (CAPSTONE) in systemic lupus erythematosus. Journal of Managed Care & Specialty Pharmacy, 28 (9), 1021-1032. (Level 5 evidence)
Putterman, C., Furie, R., Ramsey-Goldman, R., Askanase, A., Buyon, J., Kalunian, K., et al. (2014). Cell-bound complement activation products in systemic lupus erythematosus: comparison with anti-double-stranded DNA and standard complement measurements. Lupus, Science & Medicine, 1 (1). (Level 3 evidence)
Wallace, D.J., Alexander, R.V., O'Malley, T., Khosroshahi, A., Hojjati, M., Loupasakis, K., et al. (2019). Randomised prospective trial to assess the clinical utility of multianalyte assay panel with complement activation products for the diagnosis of SLE. Lupus Science and Medicine, 19, 6 (1), e000349. (Level 2 evidence)
ORIGINAL EFFECTIVE DATE: 4/9/2015
MOST RECENT REVIEW DATE: 12/14/2023
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