Description

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that causes deterioration of the joints, inflammation, loss of mobility, pain and stiffness. RA affects multiple joints, most commonly the hands, wrists and other joints such as the elbows, feet, hips, knees, neck and shoulders.

Common laboratory tests used to diagnose and monitor treatment for RA include, but may not be limited to: anti-citrullinated peptide antibodies (anti- CCP or ACPA), C- reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) and serum IgM rheumatoid factor.

Rheumatoid Arthritis: Biologic Markers and Pharmacologic Assessment

Effective Date: 07/27/2023
Revision Date: 07/27/2023
Review Date: 07/27/2023
Policy Number: HUM-0487-019

Methotrexate (MTX), a disease modifying antirheumatic drug (DMARD), is known as the gold standard therapy for long term management in the treatment of RA alone or in combination with other medications (e.g., hydroxychloroquine sulfate [Plaquenil]). Tumor necrosis factor (TNF-alpha) inhibitors, such as adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi and Simponi Aria) and infliximab (Remicade), are pharmacotherapeutic agents used for the treatment of many inflammatory conditions, including RA.

For information regarding adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi and Simponi Aria) and infliximab (Remicade), methotrexate please refer to the applicable Pharmacy Coverage Policies.

Testing

Testing has been developed or is in development to assist in diagnosing and guiding treatment decisions in RA which include, but may not be limited to, presence of autoantibodies to carbamylated proteins (e.g., Avise Anti-CarP) and panel testing for RA (e.g., RheumAssure) that evaluates many common tests (e.g., RF, CCP and 14-3-3 eta) associated with RA simultaneously and have been proposed to aid in the diagnosis of RA. (Refer to Coverage Limitations section)

Hydroxychloroquine and methotrexate polyglutamate level testing (e.g., Avise HCQ and Avise MTX) have been purported to determine how an individual metabolizes the drug and to guide dosing. (Refer to Coverage Limitations section)

Lab testing has been developed to try to identify the serum drug concentration and development of antibodies to tumor necrosis factor-alpha inhibitor (TNFi). Results may be associated with allergic reaction, determining dosage, loss of drug efficacy (e.g., Anser ADA and Anser IFX). However, most of these have not been studied in the management of RA. (Refer to Coverage Limitations section)

A molecular signature test to predict response to TNFi therapies (e.g., PrismRA) integrates 10 ribonucleic acid single nucleotide polymorphisms (RNA SNPs), 8 RNA transcripts, 2 serum proteins (C-reactive protein [CRP], anti-cyclic citrullinated protein) and 3 clinical features (sex, body mass index, patient disease assessment). (Refer to Coverage Limitations section)

Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

RA disease activity multianalyte assay (eg, Vectra DA) measures concentrations of 12 serum proteins purportedly associated with RA disease activity. These concentrations are then applied in an algorithm to estimate a disease activity score. The panel measures the following proteins: C-reactive protein (CRP), epidermal growth factor (EGF), interleukin 6 (IL-6), leptin, matrix metalloproteinase 1 (MMP-1), matrix metalloproteinase 3 (MMP-3), resistin, serum amyloid (SAA), tumor necrosis factor receptor, type 1 (TNF-R1), vascular cell adhesion molecule 1 (VCAM-1), vascular endothelial growth factor A (VEGF-A) and YKL-40. (Refer to Coverage Limitations section)

Coverage Determination

Any state mandates for tests for biologic markers for the diagnosis, management or pharmacologic assessment of RA take precedence over this medical coverage policy.

Please refer to the member’s applicable pharmacy benefit to determine benefit availability and the terms and conditions of coverage for medication for the treatment of RA.

Humana members may be eligible under the Plan for ANY of the following tests for biologic markers for the diagnosis and management of RA:

• Anti-citrullinated peptide antibodies (anti-CCP or ACPA)
• Antinuclear antibody (ANA)
• C-reactive protein (CRP)
• Erythrocyte sedimentation rate (ESR)
• Rheumatoid Factor (RF)
• Serum IgM rheumatoid factor

Coverage Limitations

Humana members may NOT be eligible under the Plan for the following tests for biologic markers or pharmacologic assessment for the diagnosis and management of RA:

• 14-3-3 eta protein; OR
• HLA typing; OR
• Levels of antibodies to adalimumab or infliximab (eg, Anser ADA and Anser IFX); OR
• Levels of hydroxychloroquine (eg, Avise HCQ); OR
• Levels of methotrexate polyglutamates (eg, Avise MTX); OR
• Molecular signature test to predict response to TNFi therapies (eg, PrismRA); OR
• Presence of autoantibodies to carbamylated proteins (eg, Avise Anti-CarP); OR
• Rheumatoid arthritis disease activity (eg, Vectra DA [81490])

These are considered experimental/investigational as they are not identified as widely used and generally accepted for the proposed uses as reported in nationally recognized peer-reviewed medical literature published in the English language.

Humana members may NOT be eligible under the Plan for panels* for RA unless ALL components in the panel are relevant to the personal history of the individual being tested. An example of a panel includes, but may not be limited to, RheumAssure. This considered experimental/investigational as it is not identified as widely used and generally accepted for the proposed uses as reported in nationally recognized peer-reviewed medical literature published in the English language.

*Individual tests within a panel may be medically necessary when the above criteria are met.

Additional information about rheumatoid arthritis may be found from the following websites:

• Background
• American College of Rheumatology
• Testing.com
• National Library of Medicine

Medical Alternatives

Alternatives to RA disease activity multianalyte assays include:

• CRP or ESR testing

Physician consultation is advised to make an informed decision based on an individual's health needs.

Rheumatoid Arthritis: Biologic Markers and Pharmacologic Assessment
Effective Date: 07/27/2023
Revision Date: 07/27/2023
Review Date: 07/27/2023
Policy Number: HUM-0487-019
Page: 5 of 8

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

Humana may offer a disease management program for this condition. The member may call the number on his/her identification card to ask about our programs to help manage his/her care.

Any CPT, HCPCS or ICD codes listed on this medical coverage policy are for informational purposes only. Do not rely on the accuracy and inclusion of specific codes. Inclusion of a code does not guarantee coverage and or reimbursement for a service or procedure.