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DESCRIPTIONHelicobacter pylori (H. pylori) is a bacterium associated with a range of gastrointestinal (GI) disorders such as peptic ulcer disease, chronic gastritis, and gastric malignancy. Eradication of H. pylori has been proven beneficial for a number of indications.
There are currently multiple regimens for treating H. pylori infection. These include proton pump inhibitors (PPIs) (as well as similar medication(s)) to suppress acid production, in combination with antibiotic treatment, consisting of one or more agents such as amoxicillin, clarithromycin, or metronidazole. These first-line regimens generally achieve eradication rates in the 70–90% range. Differences in eradication rates are dependent on the regimen used and the population being treated. Treatment failures are most often attributed to antibiotic resistance or poor patient compliance. Resistance to clarithromycin is an important factor associated with treatment failure, with high rates of treatment failure for standard first-line regimens in patients infected with clarithromycin-resistant strains of H. pylori. A 2002 survey from the U.S. estimated that 13% of H. pylori strains are resistant to clarithromycin, and that the rate of resistance was rising in comparison to earlier studies.
Genetic factors may influence the success of H. pylori treatment through effects on PPI metabolism. Individuals with polymorphisms in the CYP2C19 gene, a component of the cytochrome P450 (CYP450) system, metabolize PPIs more slowly than normal. Genetic variation in the CYP450 enzyme system is one of the most extensively studied in the field of pharmacogenomics. This family of enzymes is found in the liver and is important for metabolizing and eliminating a large number of pharmacologic agents. Differences in PPI metabolism lead to variability in gastric acid suppression, with associated variability in gastric pH, and potential impact on the efficacy of H. pylori treatment. Observational research suggests that patients who are extensive metabolizers of PPIs have lower eradication rates following standard treatment for H. pylori, compared with poor metabolizers.
There are three major CYP2C19 alleles that determine enzymatic activity, as shown in Table 1. The *1 allele is the wild-type found in most individuals, while the *2 and *3 alleles are the most common polymorphisms that are known to impact enzymatic activity. Both the *2 and *3 alleles are examples of ‘null’ alleles which have no enzymatic activity. Each null allele is caused by a single nucleotide change that results in a splice defect or a stop codon (AmpliChip package insert).
Table 1. CYP2C19 polymorphisms**
Table 2. CYP2C19 phenotypes**
**Adoted from AmpliChip package insert
Polymorphisms of the CYP2C19 gene are relatively common and vary by ethnicity. Patients with no polymorphisms of CYP2C19 have two wild-type alleles and no reduction in their ability to metabolize PPIs. These patients are typically called extensive metabolizers (EM) (Table 2). Heterozygous polymorphisms are found in 27–37% of the Caucasian population and 46–50% of the Asian population. These patients have a minor reduction in their ability to eliminate PPIs, and are called intermediate metabolizers (IM). Homozygous polymorphisms of the CYP2C19 gene are found in 3–6% of Caucasians and in 12–20% of Asians. These patients eliminate PPIs from the circulation substantially much more slowly than unaffected patients, and are termed poor metabolizers (PM).
In patients treated with PPIs, intragastric pH has been shown to correlate with CYP2C19 status. Patients homozygous for a CYP2C19 mutation (PM) exhibit a less acidic pH when compared to patients without a CYP2C19 mutation, with heterozygous patients exhibiting intermediate values. Intragastric pH has important implications for treating H. pylori. H. pylori is more sensitive to antibiotics at less acidic pH levels. Less acidic pH levels also lead to greater stability and bioavailability of antibiotics. Therefore, it is expected that treatment of H. pylori will be more successful if there is maximal suppression of gastric acid production and higher intragastric pH levels.
Therefore, it has been proposed that a pharmacogenomics-based treatment regimen individualized by CYP2C19 status may improve the success rate of treatment for H. pylori. If CYP2C19 status is known prior to treatment, adjustments can be made in the selection of PPIs and/or the dosing schedule in order to achieve optimal acid suppression in all patients. Improved eradication rates for H. pylori could lead to improved health outcomes by reducing the need for re-treatment following treatment failure, reducing recurrences of H. pylori-associated disorders, and reducing the morbidity and mortality associated with disease recurrence.
At least one commercially available genetic test, the Roche AmpliChip Cytochrome P450® Genotyping test, has been approved by the U.S. Food and Drug Administration (FDA) as a class II medical device. This test examines polymorphisms in CYP2D6 and CYP2C19 isoenzymes of the cytochrome P450 enzyme system. Approval for this device was originally granted in December 2004 as an aid in determining treatment choice and individualizing treatment dose for therapeutics that are metabolized primarily by the CYP2D6 enzyme. The use of information on CYP2C19 polymorphisms was not addressed as part of the FDA approval process.
POLICYGenotyping to determine cytochrome p450 (CYP2C19) genetic polymorphisms is considered investigational for the purpose of managing the treatment of H. pylori infection.
POLICY EXCEPTIONSFederal Employee Program (FEP) may dictate that all FDA-approved devices, drugs or biologics may not be considered investigational and thus these devices may be assessed only on the basis of their medical necessity.
Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.
The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
POLICY HISTORY3/20/2008: Policy added
7/17/2008: Reviewed and approved by the Medical Policy Advisory Committee (MPAC)
12/24/2008: Code reference section updated per 2009 CPT/HCPCS revisions
3/30/2009: Policy reviewed, no changes
07/15/2010: Policy description and statement unchanged. FEP verbiage added to the Policy Exceptions section.
08/03/2011: Policy reviewed; no changes.
01/14/2013: Added CPT code 81225 to the Code Reference section.
07/30/2015: Code Reference section updated for ICD-10. Removed the following deleted CPT codes: 83890, 83891, 83892, 83893, 83894, 83896, 83897, 83898, 83900, 83901, 83902, 83903, 83904, 83905, 83906, 83907, 83908, 83909, 83912, 83913, 83914, 88384, 88385, and 88386.
06/07/2016: Policy number added. Investigative definition updated in Policy Guidelines section.
SOURCE(S)Blue Cross and Blue Shield Association Policy # 2.04.50
CODE REFERENCEThis may not be a comprehensive list of procedure codes applicable to this policy.