Notification



Notification Issue Date:



Policy Attachment

Attachment to Policy # MA06.008b


Attachment:C

Policy #:MA06.008b

Description:Pharmacogenetic Testing to Determine Cytochrome p450 (CYP2C19) Genetic Polymorphisms for Treatment/Management of Helicobacter Pylori (H. pylori) Infection

Title:Pharmacogenetic Testing to Determine Drug Sensitivity

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.


Title: Pharmacogenetic Testing to Determine Cytochrome p450 (CYP2C19) Genetic Polymorphisms for Treatment/Management of Helicobacter Pylori (H. pylori)Infection


POLICY

Coverage is subject to the terms, conditions, and limitations of the member's Evidence of Coverage.

Pharmacogenetic testing for management of H. pylori infection treatment is experimental/investigational and, therefore, not covered because the safety and/or effectiveness of this service cannot be established by review of the available published peer-reviewed literature.

POLICY GUIDELINES

There is no Medicare coverage determination addressing this service; therefore, the Company policy is applicable.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable Evidence of Coverage, pharmacogenetic testing for H. pylori infection treatment is not eligible for payment under the medical benefits of the Company's Medicare Advantage products because the service is considered experimental/investigational and, therefore, not covered.
Services that are experimental/investigational are excluded from the Company's Medicare Advantage products. Therefore, they are not eligible for reimbursement consideration.

US FOOD AND DRUG ADMINISTRATION STATUS

Genetic testing is a laboratory procedure and is historically not regulated by the US Food and Drug Administration (FDA). Clinical Laboratory Improvement Amendments (CLIA) establishes quality standards for all laboratory testing. However, recently, the FDA is reported to be involved in the evaluation of the service of genetic testing.

DESCRIPTION

Many gastrointestinal disorders are linked to the bacterium Helicobacter pylori(H. pylori), including peptic ulcer disease, chronic gastritis, and gastric malignancy. Protein pump inhibitors (PPIs) suppress gastric acid secretion and increase antimicrobial action of antibiotics by direct action on bacteria, and by elevating the gastric pH. PPIs are frequently used in combination with antibiotic therapy such as amoxicillin, clarithromycin, or metronidazole. This treatment will usually eradicate the H. pylori infection, but factors such as antibiotic resistance and poor patient compliance may preclude the possibility of successful treatment. Individual resistance to clarithromycin is frequently associated with treatment failure when given as part of a standard first-line regimen of clarithromycin.

The CYP450 enzyme and its variations have been extensively studied for their role in metabolizing and clearing many different drugs. Genetic factors may play a role in successful treatment of H. pylori infection based on their effect on the metabolism of PPIs. Individuals with polymorphisms in CYP2C19, a gene component of cytochrome p450, may metabolize PPIs more slowly than individuals without this genetic variant. It has been proposed that a pharmacogenetics-based treatment regimen tailored to the individual based on CYP2C19 status could have a more positive impact on the eradication of H. pylori. If such status is known prior to the initiation of treatment, the ability to customize the choice of PPI and the dosing schedule may help to achieve the best gastric pH suppression and thus lead to improved bacterial eradication. Successful first-line treatment may prevent recurrence and the need for retreatment.

There is some available literature, which discusses single eradication regimens when all subjects were tested for CYP2C19 status. Eradication rates were compared among all patients, including those considered to be extensive (EM), intermediate (IM), and/or poor metabolizers (PM) of PPIs. In a study (Kang et al), 327 Korean patients with H. pylori were evaluated with a treatment regimen consisting of a PPI (pantopraxole or esomerpraxole) for 7 days and amoxicillin and clarithromycin. Eradication rates were higher in those in the PM group when compared with those in the EM group. Yet another study (Miehike et al) addressed 103 patients who had at least one failed prior treatment regimen and still retained H. pylori infection resistant to metronidazole and clarithromycin. All individuals in this study received the same treatment with moxifloxacin, rifabutlin, and esomerprazole for 7 days. Outcomes showed higher eradication rates in the PM/IM patients (93.1%) compared with the EM subjects (78.8%). There is a paucity of clinical trials that compare the strategy for genetic testing and tailored treatment to standard care. The only randomized clinical trial (Furuta et al, 2007) addressing this comparison fails to serve as definitive evidence due to a number of limitations associated with this trial, including the variations in the treatment regimen of the pharmacogenomics-based treatment group.

To date, no published guidelines have been identified that address the use of genetic testing as part of the protocol for H. pylori eradication, and additional studies are required to establish the superiority of genetic-based treatment regimen over standard therapy.

REFERENCES

Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Pharmacogenomics-based treatment of Helicobacter pylori infection. TEC Assessments. 2008; vol. 23, tab 2.

Chaudhry AS, Kochhar R, Kohli KK. Importance of CYP2C19 genetic polymorphism in the eradication of Helicobacter pylori in north Indians. Ind J Med Res. 2009;130(4):437-43.

Furuta T, Shirai N, Kodaira M, et al. Pharmacogenomics-based tailored versus standard therapeutic regimen for eradication of H. pylori. Clin Pharmacol Ther. 2007;81(4):521-8.

Furuta T, Shirai N, Takashima M, et al. Effects of genotypic differences in CYP2C19 status on cure rates for Helicobacter pylori infection by dual therapy with rabeprazole plus amoxicillin. Pharmacogenetics. 2001;11(4):341-8.

Gawronska-Szklarz B, Siuda A, Kurzawski M, et al. Effects of CYPC219, MDR1, and interleukin 1-B gene variants on the eradication rate of Helicobacter pylori infection by triple therapy with pantoprazole, amoxicillin, and metronidazole. Eur J Clin Pharmacol. 2010;66(7):681-7.

Kang JM, Kim N, Lee DH, et al. Effect of the CYP2C19 polymorphism on the eradication rate of Helicobacter pylori infection by 7-day triple therapy with regular proton pump inhibitor dosage. J Gastroenterol Hepatol. 2008;23(8 Pt 1):1287-91.

Klotz U. Impact of CYP2C19 polymorphisms on the clinical action of proton pump inhibitors (PPIs). Eur J Clin Pharmacol. 2009;65(1):1-2.

Miehlke S, Schneider-Brachert W, Kirsch C, et al. One-week once-daily triple therapy with esomeprazole, moxifloxacin, and rifabutin for eradication of persistent Helicobacter pylori resistant to both metronidazole and clarithromycin. Helicobacter. 2008;13(1):69-74.

Padol S, Yuan Y, Thabane M, et al. The effect of CYP2C19 polymorphisms on H. pylori eradication rate in dual and triple first-line PPI therapies: a meta-analysis. Am J Gastroenterol. 2006;101(7):1467-75.

Sapone A, Vaira D, Trespidi S, et al. The clinical role of cytochrome P450 genotypes in Helicobacter pylori management. Am J Gastroenterol. 2003;98(5):1010-5.

Sheu BS, Kao AW, Cheng HC, et al. Esomeprazole 40 mg twice daily in triple therapy and the efficacy of Helicobacter pylori eradication related to CYP2C19 metabolism. Aliment Pharmacol Ther. 2005;21(3):283-8.

Sheu BS, Fock KM. CYP2C19 genotypes and Helicobacter pylori eradication. J Gastroenterol Hepatol. 2008;23(8 Pt 1):1163.

Schwab M, Schaeffeler E, Klotz U, et al. CYP2C19 polymorphism is a major predictor of treatment failure in white patients by use of lansoprazole-based quadruple therapy for eradication of Helicobacter pylori. Clin Pharmacol Ther. 2004;76(3):201-9.

US Food and Drug Administration. Center for Devices and Radiological Health. AmpliChip CYP450 Clearance Letter. December 23, 2004. Available online at: http://www.accessdata.fda.gov/cdrh_docs/pdf4/k042259.pdfAccessed July 31, 2013.

Yang JC, Yang YF, Uang YS, et al. Pharmacokinetic-pharmacodynamic analysis of the role of CYP2C19 genotypes in short-term rabeprazole-based triple therapy against Helicobacter pylori. Br J Clin Pharmacol. 2009;67(5):503-10.

Zhao F, Wang J, Yang Y, et al. Effect of CYP2C19 genetic polymorphisms on the efficacy of proton pump inhibitor-based triple therapy for Helicobacter pylori eradication: a meta-analysis. Helicobacter. 2008;13(6):532-41.


Coding Table

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

Code System
Code Narrative
CPT 81225
ICD-10 N/A
ICD-10 N/A
HCPCS N/A


Version Effective Date: 07/01/2016
Version Issued Date: 07/01/2016
Version Reissued Date: 10/10/2019

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