Currentblue cross blue shield - tennesseePolicy N/A

Metabolites Markers of Thiopurines Testing – G2115

Policy governs coverage for phenotypic TPMT enzyme analysis and monitoring of thiopurine metabolite levels (6-MMRP, 6-TGN) for management of individuals on thiopurine therapy, with specified covered indications and noncovered uses. Includes applicable CPT/HCPCS codes and regulatory disclaimers.

Policy Summary

Payerblue cross blue shield - tennessee

PolicyMetabolites Markers of Thiopurines Testing – G2115

Policy CodePolicy N/A

Change TypeNo material change

Effective DateN/A

Next Review DateN/A

Key ActionVerify member benefits and document the covered indication when ordering one-time TPMT phenotypic analysis.

SourceLink

POLICY UPDATE CHANGES

No material clinical/coverage changes.

3Covered clinical scenarios (TPMT/metabolite monitoring)

2Explicitly not-covered test categories

3Procedure codes listed

Coverage Summary

This policy governs coverage for one-time phenotypic testing of thiopurine methyltransferase (TPMT) and for monitoring of thiopurine metabolite levels (6-MMRP, 6-TGN) to manage individuals on thiopurine therapy. The coverage stance is mixed: TPMT phenotypic analysis and thiopurine metabolite monitoring are covered for specific clinical scenarios (e.g., prior to initiating azathioprine/6-MP/6-TG; abnormal CBC on therapy not responsive to dose reduction; IBD with suspected toxicity or nonresponse; ALL with inadequate myelosuppression or intolerance), but these tests do not meet coverage criteria for other situations not explicitly listed.

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Medical Necessity Criteria

Covered - TPMT phenotypic analysis (one-time)

One-time phenotypic analysis of the enzyme thiopurine methyltransferase (TPMT) MEETS COVERAGE CRITERIA for any of the following situations:

ANY of the following

Prior to initiating treatment with azathioprine (AZA), mercaptopurine (6-MP) or thioguanine (6-TG).
For individuals on thiopurine therapy with abnormal complete blood count (CBC) results that do not respond to dose reduction.

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title": "Covered - TPMT phenotypic analysis (one-time)"

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Covered - Thiopurine metabolite monitoring in inflammatory bowel disease

For individuals with inflammatory bowel disease, monitoring of thiopurine metabolite levels MEETS COVERAGE CRITERIA for any of the following indications:

ANY of the following

To measure blood levels in individuals suspected of having toxic responses to AZA and/or 6-MP (e.g., hepatotoxicity or myelotoxicity).
To measure drug levels in individuals who have not responded to therapy (e.g., persistent fever, further weight loss, and bloody diarrhea).

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Covered - Thiopurine metabolite monitoring in acute lymphoblastic leukemia

For individuals with acute lymphoblastic leukemia, monitoring of thiopurine metabolite levels MEETS COVERAGE CRITERIA for any of the following situations:

ANY of the following

For individuals showing signs of a lack of myelosuppression while on therapy.
For individuals who do not tolerate thiopurines.

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title":

Not covered / Does not meet coverage criteria

The following DOES NOT MEET COVERAGE CRITERIA due to lack of sufficient published scientific literature:

ALL of the following

Phenotypic analysis of the enzyme TPMT for all other situations not addressed above.
Analysis of the metabolite markers of azathioprine and 6-mercaptopurine, including 6-methyl-mercaptopurine ribonucleotides (6-MMRP) and 6-thioguanine nucleotides (6-TGN), for all other situations not addressed above.

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Provider Actions & Billing Guidance

Documentation Required

Document indication for TPMT testing

Document that one-time TPMT phenotypic analysis is being ordered for a covered situation: either prior to initiating azathioprine, mercaptopurine, or thioguanine, or for an individual on thiopurine therapy with abnormal CBC results that do not respond to dose reduction.

82657
84433

Prior Authorization

Benefit verification required

Verify the member's benefits and any plan-specific requirements before ordering testing, since application of the coverage criteria depends on an individual's benefit coverage at the time of the request.

Denial Risk

Testing may be denied if not meeting covered indications

Claims for TPMT phenotypic analysis or thiopurine metabolite analysis for situations not listed as covered are at risk for denial as not meeting coverage criteria.

80299

Background

Thiopurines are purine antimetabolite immunomodulators used in autoimmune disease, transplant rejection, and acute lymphoblastic leukemia. Their therapeutic efficacy and toxicities (bone marrow and liver) are related to downstream metabolite levels and to TPMT enzyme activity; individual responses vary substantially. Monitoring TPMT phenotypic activity and thiopurine metabolite levels can guide dosing decisions and help identify toxicity during therapy.

Guidelines and evidence cited include AGA/ACG/CPIC/NCCN and UpToDate sources supporting TPMT and metabolite testing in specific contexts: clinical practice guidelines and technical reviews on therapeutic drug monitoring in inflammatory bowel disease, CPIC guidance for thiopurine dosing by TPMT/NUDT15 genotype, NCCN guidance for acute lymphoblastic leukemia, and UpToDate reviews on thiopurine pharmacology and pretreatment testing.

Definitions

Measured Analytes

OpenPayer

Metabolites Markers of Thiopurines Testing – G2115

Coverage Summary

Medical Necessity Criteria

Applicable Codes

Provider Actions & Billing Guidance

Background

Revision History

80299	Quantitation of therapeutic drug, not elsewhere specified.
82657	Enzyme activity in blood cells, cultured cells, or tissue, not elsewhere specified; nonradioactive substrate, each specimen.
84433	Thiopurine S-methyltransferase (TPMT).