Pathology/Lab Coding Alert

See how gene analysis can personalize medication choices.

CPT^® 2023 is keeping up with the growth in pharmacogenomic testing by adding a new Category I code and integrating six proprietary laboratory analyses (PLA) codes that came on line in recent quarterly updates.

Read on to get familiar with the latest lab tests clinicians may order to guide therapeutic decisions for medications ranging from antidepressants to withdrawal modulators.

Glossary: The following terms will be helpful in understanding the new codes.

• Pharmacogenomics (PGx): Refers to studies or testing to identify how a person’s genes may affect their response to medications.
• Genotype: The genetic makeup of the individual; specifically, the two alleles (forms) of each gene a person has inherited.
• Phenotype: The observable traits of a person due to how the genotype is expressed, and how the genes interact with the environment.

Check Out New Category I Code

By adding 81418 (Drug metabolism (eg, pharmacogenomics) genomic sequence analysis panel, must include testing of at least 6 genes, including CYP2C19, CYP2D6, and CYP2D6 duplication/deletion analysis), CPT^® 2023 provides a single new code to describe a pharmacogenomics panel of at least six genes, including those listed in the code.

The test encompasses the work of an existing code for common variants of the cytochrome P450, family 2 subfamily D polypeptide 6 (CYP2D6) gene: 81226 (CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) (eg, drug metabolism), gene analysis, common variants (eg, *2, *3, *4, *5, *6, *9, *10, *17, *19, *29, *35, *41, *1XN, *2XN, *4XN)), but also includes more rare variants and duplication/deletion analysis of the gene.

In that way, the CYP2D6 analysis described by 81418 is similar to PLA code 0070U (CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) (eg, drug metabolism) gene analysis, common and select rare variants (ie, *2, *3, *4, *4N, *5, *6, *7, *8, *9, *10, *11, *12, *13, *14A, *14B, *15, *17, *29, *35, *36, *41, *57, *61, *63, *68, *83, *xN)) that identifies common and rare variants of the as well as duplications.

Function: CYP2D6 contributes to processes that form or break down certain chemicals inside cells, so mutations may impact medication therapeutic levels, efficacy or toxicity. CYP2D6 is specifically associated with metabolism of tamoxifen, codeine, tramadol, antiarrhythmics, and some antidepressants and antipsychotics.

CYP2C19: Similar to CYP2D6, the cytochrome P450 family 2 subfamily C polypeptide 19 (CYP2C19) is involved in metabolism of many medications, specifically certain antidepressants, barbiturates, antitumor drugs, and anti-platelet drugs such as Plavix.

The 81418 panel code also encompasses the work of existing code 81225 (CYP2C19 (cytochrome P450, family 2, subfamily C, polypeptide 19) (eg, drug metabolism), gene analysis, common variants (eg, *2, *3, *4, *8, *17)).

Payment: Based on the similarity to existing codes, stakeholders at the Clinical Laboratory Fee Schedule (CLFS) annual public meeting recommended crosswalking payment for 81418 to 81225 and 0070U, because “code 81225 represents CYP2C19 common variants and code 0070U represents CYP2D6 common variants, rare variants, and duplications,” according to Cheryl James, representing Mayo Clinic Laboratories in her presentation at the CLFS annual public meeting. However, Centers for Medicare & Medicaid Services (CMS) declined to establish a payment rate on the 2023 CLFS, instead opting for local payment determinations.

See Drug Metabolism PLA Codes

Effective Oct. 1, 2022 but new to the CPT^® 2023 manual, the following four PLA codes for RighMed^® tests from OneOme^® describe different testing levels for up to 27 genes associated with drug metabolism or processing.

• 0347U (Drug metabolism or processing (multiple conditions), whole blood or buccal specimen, DNA analysis, 16 gene report, with variant analysis and reported phenotypes)
• 0348U (… 25 gene report, with variant analysis and reported phenotypes)
• 0349U (… 27 gene report, with variant analysis, including reported phenotypes and impacted gene-drug interactions)
• 0350U (… 27 gene report, with variant analysis and reported phenotypes)

Codes 0347U, 0348U, and 0350U result in a gene report that identifies the patient genotype for the genes tested (for 16, 25, or 27 genes respectively). Based on the genotype, the report predicts where the patient phenotype may fall on a scale of “poor metabolizer” to “ultrarapid metabolizer.” For drugs that metabolize to an active form, poor metabolizers may experience reduced drug efficacy, while ultrarapid metabolizers may experience drug overdose or toxicity. For drugs that are active and convert to an inactive metabolite, the reverse may be true.

The gene report for each of these codes also indicates if the patient’s genotype is atypical in a way that may result in a phenotype that could result in an abnormal reaction to the drug.

0349U: The one assay that is different from the other RightMed^® tests is 0349U. Following the genetic variant analysis in 0349U, an algorithmic analysis of the patient genotype with a database of known gene/drug interactions results in a comprehensive test report. This report identifies whether the patient might have a major, moderate, or minimal gene/drug interaction or limited pharmacogenetic impact for a host of specific drugs.

Several independent insurers have signed on to cover these tests, such as Blue Care Network (BCN). “We’re very confident that OneOme^® will help BCN achieve their precision medicine program goals and reduce total cost of care and improve patient health outcomes by reducing adverse drug reactions,” said Pat McIntyre, CEO of OneOme in a press release.

0286U: (CEP72 (centrosomal protein, 72-KDa), NUDT15 (nudix hydrolase 15) and TPMT (thiopurine S-methyltransferase) (eg, drug metabolism) gene analysis, common variants). This PLA test from RPRD Diagnostics has been effective since Jan. 1, 2022, but first appears in CPT^® 2023. The test evaluates three genes, CEP72, NUDT15, and TPMT for known mutations that may impact metabolism of thiopurines and vincristine drugs. The medications may be used to treat autoimmune conditions, but certain gene mutations may result in life-threatening reactions to the drugs.

Coding alert: Each of the preceding PGx codes lists specific genes that the test evaluates. “You should never additionally report a separate CPT^® code for one of the listed genes, because the PLA code is inclusive,” says William Dettwyler, MT-AMT, president of Codus Medicus, a laboratory coding consulting firm in Salem, Oregon.

Greet Test for Adverse Drug Reaction

PLA code 0328U (Drug assay, definitive, 120 or more drugs and metabolites, urine, quantitative liquid chromatography with tandem mass spectrometry (LC-MS/MS), includes specimen validity and algorithmic analysis describing drug or metabolite and presence or absence of risks for a significant patient-adverse event, per date of service) first appears in CPT^® 2023 following the July 1, 2022 effective date.

The test screens for 120 or more drugs and their breakdown products in a urine specimen and includes an algorithmic analysis to identify potential drug interactions or adverse drug events based on the findings. The test may help clinicians monitor medication compliance and evaluate potential risk of drug interactions.