Medical Policy: 02.04.68 

Original Effective Date: September 2017 

Reviewed: June 2021 

Revised: June 2021 

 

Notice:

This policy contains information which is clinical in nature. The policy is not medical advice. The information in this policy is used by Wellmark to make determinations whether medical treatment is covered under the terms of a Wellmark member's health benefit plan. Physicians and other health care providers are responsible for medical advice and treatment. If you have specific health care needs, you should consult an appropriate health care professional. If you would like to request an accessible version of this document, please contact customer service at 800-524-9242.

 

Benefit Application:

Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.

 

This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.

 

Description:

This medical policy addresses the use of the following biomarker and multiplex autoantigen microarray testing for autoimmune disease including the following:

  • Multi-biomarker disease activity (MBDA) blood testing that produces a score designed to assess rheumatoid arthritis (RA) disease actively, an example is the Vectra DA blood test (Crescendo Biosicence, Inc.); and
  • Biomarker testing for systemic lupus erythematous (SLE) to assist in diagnosis, prognosis and monitoring with proprietary algorithms and/or index scores, examples of this testing include AVISE SLE, AVISE SLE Prognostic, AVISE CTD Assay, and AVISE Lupus (Exagen, Inc); and
  • Multiplex autoantigen microarray testing for evaluation of systemic lupus erythematous (SLE), The technology involves testing for multiple antibodies associated with SLE at the same time and may involve the use of proprietary algorithm to determine a risk score, an example of this testing includes SLE-Key Rule Out Tests (ImmunoArray).  

 

Rheumatoid Arthritis (RA)

Rheumatoid arthritis (RA) is characterized by chronic joint inflammation leading to painful symptoms, progressive joint destruction, and loss of function. The disorder is relatively common and associated with a high burden of morbidity for affected patients.

 

Treatment of RA has undergone a shift from symptom management to a more proactive strategy of minimizing disease activity and delaying disease progression. The goal of treatment is to reduce irreversible joint damage that occurs from ongoing joint inflammation and synovitis by keeping disease activity as low as possible. The availability of an increasing number of effective disease -modifying anti-rheumatic drugs has made achievement of remission, or sustained low disease activity, a feasible goal in a large proportion of patients with RA. This treatment strategy has been called a “tight control” approach.

 

Assessment of disease activity in rheumatoid arthritis is an important component of management because a main goal of treatment is to maintain low disease activity or remission. There are a variety of available instruments for measuring rheumatoid arthritis disease activity. They use combinations of physical exam findings, radiologic results, and serum biomarkers to construct a disease activity score. There are more than 60 methods of measuring disease activity in individuals with RA. An expert panel on RA determined the following 6 measures were the most useful and feasible in a clinical setting: Clinical Disease Activity Index [CDAI], Disease Activity Score with 28 joints (DAS28), Patient Activity Scale, Patient Activity Scale II, Routine Assessment of Patient Index Data 3 (RAPID3), and Simplified Disease Activity Index (SDAI). Rheumatologists usually use four blood tests in the diagnosis of RA. These blood tests are the Sedimentation rate (ESR), C-reactive protein (CRP), Rheumatoid Factor, and the anti-CCP. The ESR and the CRP, both inflammatory markers, are also used in the ongoing monitoring of RA to assess your level of inflammation.

 

Multi-Biomarker Disease Activity (MBDA) Testing for Rheumatoid Arthritis (RA)

A multibiomarker disease activity (MBDA) instrument is a disease activity measure that is comprised entirely of serum biomarkers. The Vectra DA test is a commercially available MBDA blood test that uses 12 biomarkers to construct a disease activity score ranging from 1 (low disease activity) to 100 (high disease activity).

 

Vectra DA Test 

The Vectra DA test consists of 12 individual biomarkers:

  • Interleukin-6
  • Tumor necrosis factor receptor type I
  • Vascular cell adhesion molecule 1
  • Epidermal growth factor
  • Vascular endothelial growth factor A
  • YKL-40
  • Matrix metalloproteinase 1
  • Matrix metalloproteinase 3
  • C-reactive protein
  • Serum amyloid A
  • Leptin
  • Resistin 

 

The Vectra DA test scores range from 1 to 100. Categories of scores were constructed to correlate with the DAS28-CRP scale:

  • 45-100: high disease activity
  • 30-44: moderate disease activity
  • 1-29: low disease activity 

 

Fleischmann et. al. evaluated the ability of Vectra DA to measure disease activity in participants of the Abatacept Versus Adalimumab Comparison in Biologic-Naive RA Subjects with Background Methotrexate (AMPLE) trial. In the AMPLE trial (Schiff, 2014), a total of 646 subjects naïve to biological agents were randomized to receive abatacept (n=318) or adalimumab (n=328). Multi-biomarker disease activity (MBDA) results were available for 259 and 265 subjects, respectively. No association was found between the MBDA score and disease activity as defined by American College of Rheumatology (ACR) recommended disease activity measures (CDAI, SDAI, DAS28-C-reactive protein, or Routine Assessment of Patient Index Data with 3 measures [RAPID-3]) in either treatment group. The authors concluded:

These findings indicated that the MBDA score should not be used to guide RA management decisions, particularly in patients treated with abatacept or adalimumab as a first biologic agent.  Treatment decisions in RA should be based on clinical judgment, utilizing the disease activity measures recommended by the ACR for point-of-care clinical use.

 

For individuals who have rheumatoid arthritis (RA) who receive the Vectra DA test, the evidence includes post hoc analyses of archived serum samples from randomized controlled trials and prospective cohort studies. The published data is conflicting as to whether or not multi-biomarker disease activity (MBDA) blood tests, such as the Vectra DA, perform as well as other RA disease markers. There is insufficient published evidence indicating that treatment decisions can be influenced by MBDA test scores, and insufficient evidence demonstrating the effect of the MBDA testing on net health outcomes.

 

Biomarker Panel Testing for Systemic Lupus Erythematosus (SLE)

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease (CTD) that can be difficult to diagnose because patients often present with diverse, nonspecific symptoms that overlap with other CTDs; to further complicate matters, commonly used laboratory tests are not highly accurate. Moreover, similar symptoms may also present themselves in patients with fibromyalgia.

 

Currently, differential diagnosis depends on a combination of clinical signs and symptoms and individual laboratory tests. In 2019, new classification criteria endorsed by the European League Against Rheumatism (EULAR) and the ACR were developed and validated. The 2019 EULAR/ACR classification criteria requires, a positive ANA as an entry criterion. For those with a positive ANA, additive criteria are assessed in 7 clinical and 3 immunological domains. Weighted criteria (ranging from 2 to 10 points) are evaluated within each domain, with only the highest weighted criterion in a specific domain counting towards the total score. The weighted feature allows for criteria that are more tightly associated with SLE to contribute more heavily to the overall score. A classification of SLE requires a total score of ≥10 points.

 

The EULAR/ACR classification criteria are as follows:

    • Entry criterion: ANA at a titer of ≥1:80 on HEp-2 cells or an equivalent positive test
    • If entry criterion is present, apply additive criteria (weight):
      • Constitutional: fever (2)
      • Hematologic: leukopenia (2), thrombocytopenia (4), autoimmune hemolysis (4)
      • Neuropsychiatric: delirium (2), psychosis (3), seizure (5)
      • Mucocutaneous: non-scarring alopecia (2), oral ulcers (2), subacute cutaneous or discoid lupus (4), acute cutaneous lupus (6)
      • Serosal: pleural or pericardial effusion (5), acute pericarditis (6)
      • Musculoskeletal: joint involvement (6)
      • Renal: proteinuria >0.5 g/24 h (4), renal biopsy Class II or V lupus nephritis (8), renal biopsy Class III or IV lupus nephritis (10)
      • Antiphospholipid antibodies: anti-cardiolipin antibodies or anti-β2GP1 antibodies or lupus anticoagulant (2)
      • Complement proteins: low C3 or low C4 (3), low C3 and low C4 (4)
      • SLE-specific antibodies: antibodies to double stranded DNA (anti-dsDNA) or antibodies to Smith antigen (anti-sm) (6)

     

    To date, the most common laboratory tests performed in the diagnosis of SLE are serum ANA, and if this is positive, tests for anti-dsDNA and anti-Sm. ANA tests are highly sensitive (i.e., with a high negative predictive value) but have low specificity and relatively low positive predictive value, particularly when the ANA is positive at a low level. Specificity of testing can be increased by testing for specific antibodies against individual nuclear antigens (extractable nuclear antigens, or ENAs) to examine the “pattern” of ANA positivity. These include antigens against single and double-stranded DNA, histones, Sm, Ro, La, and RNP. The presence of anti-dsDNA or anti-Sm is highly specific for SLE because few patients without SLE test positive; however, neither of these tests have high sensitivity (Suresh, 2007). The presence of other antibody patterns may indicate the likelihood of alternate diagnoses. For example, the presence of Ro and La antibodies suggests Sjogren syndrome, while the presence of antihistone antibodies suggests drug-induced lupus.  

     

    More accurate laboratory tests for systemic lupus erythematosus (SLE) could facilitate diagnosis, prognosis and management. Recently, laboratory-developed, diagnostic panel tests with proprietary algorithms and/or index scores for the diagnosis of SLE have become commercially available. AVISE testing offers next-generation insight autoimmune lab tests to include the following:

     

        • AVISE CTD Assay: All markers reported in AVISE CTD are carefully selected to provide maximum performance in the diagnosis of SLE and diseases that mimic lupus. The AVISE CTD assay contains 22 different tests. It combines 2 smaller panels, a 10-marker panel that includes common SLE tests, as well as cell-bound complement activation products and a 12- marker panel that focuses on connective tissue diseases (CTDs) to help distinguish SLE from other CTDs. Avise CTD includes nuclear antigen antibody markers to help distinguish CTD, a rheumatoid arthritis panel to rule-in or rule-out rheumatoid arthritis, an antiphospholipid syndrome panel to assess risk for thrombosis and cardiovascular events, and a thyroid panel to help rule-in or rule-out Graves disease and Hashimoto's disease.
        • AVISE Lupus: The AVISE Lupus test is a 10-marker diagnostic test containing Cell-Bound Complement Activation Products (CB-CAPs) and other SLE associated markers designed to aid healthcare providers in a timely differential diagnosis of SLE.
        • AVISE SLE Monitor: The AVISE SLE Monitor is a unique combination of 6 specialized biomarkers include EC4d and PC4d to help assess patients with SLE.
        • AVISE SLE Prognostic: The AVISE SLE Prognostic test is a 10-marker panel developed to help assess an SLE patient’s risk for their potential risk for thrombosis, cardiovascular events, lupus nephritis and neuropsychiatric lupus.

     

    Panel tests for systemic lupus erythematosus (SLE) include markers that are standard in the work-up of SLE, but also contain novel markers, most notably cell-bound complement activation products (CB-CAPs). The accuracy of CB-CAPs in establishing a diagnosis of SLE is not known, nor is the use of these novel biomarkers recommended in clinical practice guidelines. In addition to reporting the results of the panel of tests, an index score is reported that rates how suggestive the results of the panel are of a diagnosis of SLE. Information is not available on how this index score is calculated, nor is it known how this score performs in diagnosing SLE compared with currently accepted clinical and laboratory criteria. Finally, the utility of assessing multiple biomarkers simultaneously, rather than the more commonly performed sequential testing, is unknown. The evidence is insufficient to determine the effects of the technology on net health outcomes.

     

    Multiplex Autoantigen Microarray Testing for Systemic Lupus Erythematosus (SLE)

    Currently one test the SLE-key rule-out test (ImmunoArray) is designed to rule-out the likelihood of a systemic lupus erythematous (SLE) diagnosis.  

     

    The index score, calculated using a proprietary algorithm, rates how suggestive test results are of SLE. Although there is information on cutoffs used to indicate positivity for individual markers, information is not available on how precisely the index score is calculated. The score can range from -5 (highly nonsuggestive of SLE) to 5 (highly suggestive of SLE) and a score of -0.1 to 0.1 is considered indeterminate.

     

    Two industry-funded studies evaluating the SLE-key test have been published. The available published literature on the SLE-key rule-out test is limited in that it includes samples only from individuals already diagnosed with SLE or healthy people, and not from the population most likely to be tested in clinical practice, individuals with suspected SLE. The initial development and validation study included an even more selected population, females between the ages of 18 and 60. Moreover, the impact of the test on patient management such as reducing the need for other tests or permitting an earlier diagnosis has not been studied. Furthermore, data are not available on the impact of SLE-key Rule-Out testing on health outcomes. The evidence is insufficient to determine the effects of the technology on net health outcomes.

     

    Practice Guidelines and Position Statements

    American College of Rheumatology

    In the 2015 American College of Rheumatology guidelines on the treatment of rheumatoid arthritis, ACR endorsed the following measures of disease activity: Patient Activity Scale, Routine Assessment of Patient Index Data 3, Clinical Disease Activity Index, Disease Activity Score 28, and Simplified Disease Activity Index. The guidelines indicated that other measures are available to clinicians, but that including the new measures was out of scope.

     

    European League Against Rheumatism

    The European League Against Rheumatism (2017) updated its guidelines on the management of early arthritis. The League recommended that arthritis activity be assessed at 1- to 3-month intervals to determine target treatment. “Monitoring of disease activity should include tender and swollen joint counts, patient and physician global assessments, erythrocyte sedimentation rate, and C reactive protein, usually by applying a composite measure.” Composite measures recommended include the Disease Activity Score with 28 joints, Clinical Disease Activity Index, and Simplified Disease Activity Index. One item on the research agenda recommended by the League was to evaluate new biomarkers and multibiomarkers for the prognosis and treatment in early arthritis.

     

    National Institute for Health and Clinical Excellence (NICE)

    Rheumatoid arthritis in adults: management:

    NICE recommends monthly monitoring of CRP and disease activity until remission or low disease activity. Remission is defined as a DAS28 score of under 2.6, and low is defined as a DAS28 score of under 3.2. NICE does not mention biomarkers in its recommendations for research (NICE, 2018).

     

    Systematic Lupus International Collaborating Clinics

    In 2012, the Systemic Lupus International Collaborating Clinics (SLICC), an international group of researchers, developed revised criteria for diagnosing SLE. These criteria include more laboratory tests than the earlier ACR criteria, including elements of the complement system. Patients are classified as having SLE if they satisfy 4 or more of the 18 criteria below, including at least 1 clinical criterion and 1 immunologic criterion, or they have biopsy-confirmed nephritis compatible with SLE and with ANA or antiDNA antibodies. In a sample of 690 patients, the SLICC criteria had a sensitivity of 97% and a specificity of 84% for diagnosing SLE, whereas the ACR criteria applied to the same sample had a sensitivity of 83% and a specificity of 96%. It is not clear how well-accepted the SLICC recommendations are in the practice setting. The SLICC criteria are outlined below.

     

    Clinical and Immunologic Criteria

    Clinical Criteria
        • Acute cutaneous lupus (including but not limited to lupus malar rash)
        • Chronic cutaneous lupus (including but not limited to discoid rash)
        • Oral ulcers
        • Nonscarring alopecia in the absence of other causes
        • Synovitis involving ≥ 2 joints, characterized by swelling or effusion or and ≥ 30 min of morning stiffness
        • Serositis
        • Renal: excessive protein in the urine or cellular casts in the urine
        • Neurologic disorder: seizures, psychosis, mononeuritis complex, or peripheral, or cranial neuropathy
        • Seizures
        • Hemolytic anemia
        • Leukopenia or lymphopenia
        • Thrombocytopenia 

     

    Immunologic Criteria 
        • Antinuclear antibody above laboratory reference range
        • Antibodies to double-stranded DNA above laboratory reference range
        • Antibodies to Smith nuclear antigen
        • Antiphospholipid antibody
        • Low complement (low C3, low C4, or low CH150)
        • Direct Coombs tests in the absence of hemolytic anemia 

     

    As previously noted, the SLICC classification system includes a wider range of laboratory tests than the ACR criteria. To date, the most common laboratory tests performed in the diagnosis of SLE are serum ANA, and, if positive, tests for anti-dsDNA and anti-Sm.

     

    Canadian Rheumatology Association (CRA)

    In the 2018 CRA guidelines and recommendations for assessing and monitoring SLE, they state, “Best clinical practice includes a complete history and physical examination at baseline, with laboratory monitoring possibly including but not limited to complete blood count (CBC), liver enzymes, creatine kinase, creatinine and estimated glomerular filtration rate (eGFR), urine routine/microscopic (urinalysis), urine protein-creatinine ratio, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), complements (C3, C4), anti-dsDNA, antinuclear antibodies, antibodies to extractable nuclear antigens, antiphospholipid antibodies (aPL), lupus anticoagulant (LAC), anticardiolipin (aCL), anti-β2-glycoprotein I (anti-β2-GPI), and lipid profile. Follow-up (sic) laboratory monitoring will depend on the patient’s clinical status and may include CBC, eGFR, urinalysis, urine protein-creatinine ratio, CRP, and/or ESR, C3, C4, and anti-dsDNA antibodies.

     

    American Academy of Pediatrics (AAP, 2019)

    The AAP released guidelines through Choosing Wisely. In it, they state “Do not order antinuclear antibody (ANA) and other autoantibody testing on a child unless there is strong suspicion or specific signs of autoimmune disease”

     

    Regulatory Status

    Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests must meet the general regulatory standards of the Clinical Laboratory Improvement Act (CLIA). These tests are available under the auspices of CLIA. Laboratories that offer laboratory-developed tests must be licensed by the CLIA Clinical for high-complexity testing. To date, the U.S. Food and Drug Administration has chosen not to require any regulatory review of this test.

     

    Prior Approval:

    Not applicable

     

    Policy:

    The use of multi-marker biomarker disease activity (MBDA) testing using Vectra DA for rheumatoid arthritis (RA) is considered investigational for all indications. The evidence is insufficient to determine the effects of the technology on net health outcomes.

     

    Serum biomarker panel testing with proprietary algorithms and/or index scores for the diagnosis, prognosis or management of systemic lupus erythematosus (SLE), including, but not limited to the following, are considered investigational for all indications because the evidence is insufficient to determine the effects of the technology on net health outcomes:

    • AVISE CTD Assay
    • AVISE Lupus
    • AVISE SLE Monitor
    • AVISE SLE Prognostic

     

    Multiplex autoantigen microarray testing to screen for, diagnose or manage systemic lupus erythematous (SLE) using SLE-key rule-out test is considered investigational for all indications. The evidence is insufficient to determine the effects of the technology on net health outcomes.

     

    Procedure Codes and Billing Guidelines:

    To report provider services, use appropriate CPT* codes, Alpha Numeric (HCPCS level 2) codes, Revenue codes and / or diagnosis codes.

    • 81490 Autoimmune (rheumatoid arthritis), analysis of 12 biomarkers using immunoassays, utilizing serum, prognostic algorithm reported as a disease activity score (Vectra DA)
    • 81479 Unlisted molecular pathology procedure (may be utilized for the following: AVISE CTD Assay, AVISE Lupus, AVISE SLE Monitor, AVISE SLE Prognostic)
    • 81599 Unlisted multianalyte assay with algorithmic analysis (may be utilized for the following: AVISE CTD Assay, AVISE Lupus, AVISE SLE Monitor, AVISE SLE Prognostic)
    • 84999 Unlisted chemistry procedure (may be utilized for the following: AVISE CTD Assay, AVISE Lupus, AVISE SLE Monitor, AVISE SLE Prognostic)
    • 0062U Autoimmune (systemic lupus erythematosus), IgG and IgM analysis of 80 biomarkers, utilizing serum, algorithm reported with a risk score (SLE-Key Rule-Out Test)

     

    Selected References:

    • Upchurch KS, Kay J. Evolution of treatment for rheumatoid arthritis. Rheumatology (Oxford). Dec 2012;51 Suppl 6:vi28-36. PMID 23221584
    • Schoels M, Knevel R, Aletaha D, et al. Evidence for treating rheumatoid arthritis to target: results of a systematic literature search. Ann Rheum Dis. Apr 2010;69(4):638-643. PMID 20237123
    • Anderson J, Caplan L, Yazdany J, et al. Rheumatoid arthritis disease activity measures: American College of Rheumatology recommendations for use in clinical practice. Arthritis Care Res (Hoboken). May 2012;64(5):640-647. PMID 22473918
    • Gaujoux-Viala C, Mouterde G, Baillet A, et al. Evaluating disease activity in rheumatoid arthritis: which composite index is best? A systematic literature analysis of studies comparing the psychometric properties of the DAS, DAS28, SDAI and CDAI. Joint Bone Spine. Mar 2012;79(2):149-155. PMID 21680221
    • Salaffi F, Ciapetti A, Gasparini S, et al. The comparative responsiveness of the patient self-report questionnaires and composite disease indices for assessing rheumatoid arthritis activity in routine care. Clin Exp Rheumatol. Nov-Dec 2012;30(6):912-921. PMID 22935335
    • 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 (Hoboken). Dec 2012;64(12):1794-1803. PMID 22736476
    • Crescendo Bioscience Inc. Vectra DA Patient Guide. 2017 Accessed May 24, 2017.
    • Eastman PS, Manning WC, Qureshi F, et al. Characterization of a multiplex, 12-biomarker test for rheumatoid arthritis. J Pharm Biomed Anal. Nov 2012;70:415-424. PMID 22749821
    • Centola M, Cavet G, Shen Y, et al. Development of a multi-biomarker disease activity test for rheumatoid arthritis. PLoS One. 2013;8(4):e60635. PMID 23585841
    • Hirata S, Dirven L, Shen Y, et al. A multi-biomarker score measures rheumatoid arthritis disease activity in the BeSt study. Rheumatology (Oxford). Jul 2013;52(7):1202-1207. PMID 23392591 
    • Markusse IM, Dirven L, van den Broek M, et al. A multibiomarker disease activity score for rheumatoid arthritis predicts radiographic joint damage in the BeSt study. J Rheumatol. Nov 2014;41(11):2114-2119. PMID 25128518
    • Bakker MF, Cavet G, Jacobs JW, et al. Performance of a multi-biomarker score measuring rheumatoid arthritisdisease activity in the CAMERA tight control study. Ann Rheum Dis. Oct 2012;71(10):1692-1697. PMID 22596166
    • Hambardzumyan K, Bolce R, Saevarsdottir S, et al. Pretreatment multi-biomarker disease activity score and radiographic progression in early RA: results from the SWEFOT trial. Ann Rheum Dis. Jun 2015;74(6):1102-1109. PMID 24812287
    • Hambardzumyan K, Bolce RJ, Saevarsdottir S, et al. Association of a multibiomarker disease activity score at multiple time-points with radiographic progression in rheumatoid arthritis: results from the SWEFOT trial. RMD Open. 2016;2(1):e000197. PMID 26958364
    • Fleischmann R, Connolly SE, Maldonado MA, et al. Brief Report: Estimating disease activity using Multi-Biomarker Disease Activity Scores in rheumatoid arthritis patients treated with abatacept or adalimumab. Arthritis Rheumatol. Sep 2016;68(9):2083-2089. PMID 27111089
    • Davis JM, 3rd. Editorial: The Multi-Biomarker Disease Activity Test for rheumatoid arthritis: is it a valid measure of disease activity? Arthritis Rheumatol. Sep 2016;68(9):2061-2066. PMID 27111349
    • Curtis JR, Wright GC, Strand V, et al. 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. Arthritis Rheumatol. Apr 2017;69(4):863-865. PMID 27813312
    • Fleischmann R, Connolly SE, Maldonado MA, et al. Reply. Arthritis Rheumatol. Apr 2017;69(4):867-868. PMID 27992708
    • Rech J, Hueber AJ, Finzel S, et al. Prediction of disease relapses by multibiomarker disease activity and autoantibody status in patients with rheumatoid arthritis on tapering DMARD treatment. Ann Rheum Dis. Sep 2016;75(9):1637-1644. PMID 26483255
    • Singh JA, Saag KG, Bridges SL, Jr., et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. Jan 2016;68(1):1-26. PMID 26545940
    • Li W, Sasso EH, Emerling D, et al. Impact of a multi-biomarker disease activity test on rheumatoid arthritis treatment decisions and therapy use. Curr Med Res Opin. Jan 2013;29(1):85-92. PMID 23176063
    • Anderson J, Caplan L, Yazdany J, Robbins ML, Neogi T, Michaud K, et al. Rheumatoid arthritis disease activity measures: American College of Rheumatology recommendations for use in clinical practice. Arthritis Care Res (Hoboken) 2012;64:640–7.
    • American College of Rheumatology (ACR). The 1982 Revised Criteria for Classification of Systemic Lupus Erythematosus.
    • Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. Sep 1997;40(9):1725. PMID 9324032
    • Guidelines for referral and management of systemic lupus erythematosus in adults. American College of Rheumatology Ad Hoc Committee on Systemic Lupus Erythematosus Guidelines. Arthritis Rheum. Sep 1999;42(9):1785-1796. PMID 10513791
    • Dervieux T, Conklin J, Ligayon JA, et al. Validation of a multi-analyte panel with cell-bound complement activation products for systemic lupus erythematosus. J Immunol Methods. Jul 2017;446:54-59. PMID 28389175
    • UpToDate, Inc. Assessment of rheumatoid arthritis activity in clinical trials and clinical practice. Updated February 2018. Accessed July 10, 2018. 
    • UpToDate, Inc. HLA and other susceptibility genes in rheumatoid arthritis. Updated June 2018.
    • Krabbe S, Bolce R, Brahe CH, et al. Investigation of a multi-biomarker disease activity score in rheumatoid arthritis by comparison with magnetic resonance imaging, computed tomography, ultrasonography, and radiography parameters of inflammation and damage. Scand J Rheumatol. Sep 2017;46(5):353-358. PMID 27682742
    • Combe B, Landewe R, Daien CI, et al. 2016 update of the EULAR recommendations for the management of early arthritis. Ann Rheum Dis. Jun 2017;76(6):948-959. PMID 27979873
    • Putterman C, Wu A, Reiner-Benaim A, et al. SLE-key® Rule-Out Serologic Test for Excluding the Diagnosis of Systemic Lupus Erythematosus: Developing the ImmunArray iCHIP®. Journal of immunological methods. 2016;429:1-6. doi:10.1016/j.jim.2015.12.003. 
    • Myriad RBM, Biomarker Solutions product description. 
    • Taylor, P., & Maini, R. (2017). Investigational biologic markers in the diagnosis and assessment of rheumatoid arthritis. In J. O'Dell (Ed.), UpToDate. Waltham. MA. 
    • National Institute for Health and Care Excellence (NICE) guideline on rheumatoid arthritis in adults: management (2018).
    • AAP. (2019). American Academy of Pediatrics – Section on Rheumatology. 
    • Aringer, M., Costenbader, K., Daikh, D., Brinks, R., Mosca, M., Ramsey-Goldman, R., Johnson, S. R. (2019). 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis, 78(9), 1151-1159. doi:10.1136/annrheumdis-2018-214819 
    • Bloch, D. (2019). Measurement and clinical significance of antinuclear antibodies - UpToDate. UpToDate. 
    • Kim, J., Lee, W., Kim, G. T., Kim, H. S., Ock, S., Kim, I. S., & Jeong, S. (2019). Diagnostic utility of automated indirect immunofluorescence compared to manual indirect immunofluorescence for anti-nuclear antibodies in patients with systemic rheumatic diseases: A systematic review and metaanalysis. Semin Arthritis Rheum, 48(4), 728-735. doi:10.1016/j.semarthrit.2018.03.015
    • Vectra
    • Chernoff P, et al. Determination of the minimally important difference (MID) in multi-biomarker disease activity (MBDA) test scores: impact of diurnal and daily biomarker variation patterns on MBDA scores. Clin Rheumatol. 2018; Aug 29
    • Curtis JR, et al. Uptake and Clinical Utility of the Multi-Biomarker Disease Activity Testing in the U.S. J Rheumatol. 2018; Nov 15

     

    Policy History:

    • June 2021 - Annual Review, Policy Revised
    • June 2020 - Annual Review, Policy Revised
    • September 2019 - Annual Review, Policy Revised
    • September 2018 - Annual Review, Policy Revised
    • September 2017 - New Policy

    Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

     

    *CPT® is a registered trademark of the American Medical Association.