CurrentBlue Cross Blue Shield - Rhode IslandPolicy N/A

Measurement of antibodies to TNF blocking agents

This policy addresses coverage and coding for laboratory measurement of antibodies to tumor necrosis factor (TNF) blocking agents (including testing that may measure drug levels) for members of Blue Cross Blue Shield - Rhode Island/BlueCHiP for Medicare.

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyMeasurement of antibodies to TNF blocking agents

Policy CodePolicy N/A

Change TypeNo material change

Effective DateJan 1, 2020

Next Review DateN/A

Key ActionDo not expect prior authorization; verify member benefits and document rationale if testing despite policy stating tests are not covered or are not medically necessary.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

Not coveredBlueCHiP for Medicare coverage stance

Not medically necessaryCommercial products coverage stance

4 drugsTNF or related biologics discussed

3 entriesCoding entries provided (including unlisted)

CitedImmunogenicity evidence

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Coverage Criteria

Not Medically Necessary / Not Covered

Covered when ALL of the following are met:

Policy coverage conclusion: Measurement of antibodies to TNF blocking agents, alone or combined with serum drug level measurement, is not covered for BlueCHiP for Medicare and is not medically necessary for Commercial products because evidence is insufficient to determine effects on health outcomes.

Limited assay validation, inconsistent thresholds, and lack of demonstrated management benefit cited.

Benefits and coverage for measurement of antibodies to tumor necrosis factor (TNF) blocking agents may vary by group contract. Refer to the member’s Evidence of Coverage, Subscriber Agreement, or employer agreement to determine whether this service is designated as not medically necessary or not a covered benefit for a specific plan.

If a service is determined to be not medically necessary, or if a medically necessary service is a non‑covered benefit under the member’s contract, the service may be denied and the provider may not bill the member unless the member has been informed and has agreed in advance to assume financial responsibility. Verify member benefits and any applicable participation agreement provisions before providing services that could result in member liability.

For Commercial products, measurement of antibodies to TNF blocking agents — either alone or combined with serum drug level measurement — is considered not medically necessary because the evidence is insufficient to demonstrate an effect on health outcomes. Available studies are limited, assays are heterogeneous with variable validation, and informative antibody thresholds have not been established to guide management decisions.

This policy is provided for informational purposes and is not a guarantee of payment. Providers should verify member‑specific benefits via the provider call center and comply with participation agreements. If a service is determined not to be medically necessary or is a non‑covered benefit, obtain the member’s informed agreement before proceeding if the member will be billed.

Coding and Billing Codes

Covered CPT Codes (listed)CPT

80145

Adalimumab (effective 1/1/2020)

Not covered / considered not medically necessaryCPTNot Covered

80230

Infliximab (effective 1/1/2020)

Not covered / considered not medically necessaryCPTNot Covered

80280

Vedolizumab (effective 1/1/2020)

Unlisted chemistry procedureCPT

84999

Unlisted chemistry procedure (used when no code assigned for ustekinumab antibody measurement)

Provider Actions and Billing Guidance

Prior Authorization

Prior Authorization Not Applicable

Prior authorization not required for services described in this policy. Verify prior authorization requirements only when treating members whose benefit documents or plan-specific rules indicate otherwise.

Prior authorization: Not applicable

Billing Rule

Payment Not Guaranteed — Verify Authorization

This policy is provided for informational purposes and is not a guarantee of payment. Always verify that an authorization (if required by the member's plan) is active and applicable to the requested service prior to delivering care or submitting claims.

Payment not guaranteed; verify authorization prior to service

Background

Tumor necrosis factor (TNF) inhibitors (for example, infliximab and adalimumab, among others) are used to treat a range of inflammatory conditions. A substantial proportion of patients either do not respond initially (primary nonresponse) or lose response over time (secondary loss of response). Development of antidrug antibodies (ADA) can neutralize the biologic or increase its clearance, contributing to decreased drug levels, therapeutic failure, and infusion or injection reactions. Although immunogenicity is a recognized phenomenon and cited in multiple systematic reviews and studies, assay methods vary (ELISA, radioimmunoassay, homogeneous mobility shift assays) and validation across tests is limited, so the clinical utility of routine ADA or drug‑level testing to improve outcomes has not been established.

Definitions and Assay Information

Antidrug antibodies (ADA) — definition and clinical impact

DefinitionAntidrug antibodies (ADA) are antibodies developed against biologic agents that may neutralize the drug or increase its clearance, potentially causing secondary loss of response and infusion/injection reactions.

Clinical impact - treatment failureADA have been associated with secondary nonresponse to TNF inhibitors by neutralizing drug effect or enhancing drug clearance.

Clinical impact - safetyADA are associated with injection-site and infusion-site reactions that can affect tolerability of therapy.

Measurement challengesDetection and quantitative measurement of ADA is difficult due to drug interference and variability among assays, limiting interpretation.

Assay types — ELISA, radioimmunoassay, homogeneous mobility shift assays and limitations

ELISA (enzyme-linked immunosorbent assay)

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyMeasurement of antibodies to TNF blocking agents

Policy CodePolicy N/A

Change TypeNo material change

Effective DateJan 1, 2020

Next Review DateN/A

Key ActionDo not expect prior authorization; verify member benefits and document rationale if testing despite policy stating tests are not covered or are not medically necessary.

SourceLink

On This Page

Billing Rule

Member Financial Responsibility if Service Not Covered

When a service described in this policy is determined to be not medically necessary or is a non‑covered benefit under the member's contract, the member may be financially responsible for the cost of the service if the provider and member agree in advance to proceed.

Member financial responsibility may apply for non‑covered or not medically necessary services
Obtain informed financial consent from the member before providing non‑covered services

Note

Treatment Sequencing (Informational)

Options for management of secondary loss of response to anti‑TNF therapy include shortening the interval between doses, increasing the dose, switching to a different anti‑TNF agent (if loss of response persists after dose escalation), or switching to a non–anti‑TNF agent. These are informational treatment sequencing options and not coverage criteria.

Treatment sequencing options: dose interval shortening, dose increase, switch anti‑TNF agent, switch to non‑anti‑TNF agent

First-generation assays that can measure ADA only in the absence of detectable drug because circulating drug interferes with the assay.

RadioimmunoassayAn alternative technique with disadvantages including test complexity, prolonged incubation, and handling of radioactive material.

Homogeneous mobility shift assay (fluid-phase)Newer assays (eg, Prometheus Anser tests) that can detect ADA in the presence of measurable drug and measure both drug concentration and ADA; validation across assays is limited.

Assay validation limitationStudies evaluating concordance and validation among different assay types are lacking, making interstudy comparisons difficult.

Anti-drug antibodies / immunogenicity — summary of immunogenicity impact and referenced transient responses

Immunogenicity effect on pharmacokineticsAntibody responses to TNF inhibitors can impact pharmacokinetics, often increasing clearance and reducing serum drug levels.

Association with therapeutic failureConsiderable evidence links ADA with secondary nonresponse and therapeutic failure, and antibody development may complicate switching between agents.

Transient antibody responsesSome studies report that antibody responses (eg, to infliximab) can be transient, with implications for interpretation of single time-point measurements.

Evidence baseMultiple systematic reviews, observational studies, and trials have examined immunogenicity and its clinical impact, but clinical utility of testing to improve outcomes is not established.