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L.2.04.457
Metabolites of some direct-acting antiviral (DAA) medications can be measured in the urine. Measurement of urine drug levels reflects serum drug levels and thus has the potential for use as a test of adherence.
While DAA medications have been a breakthrough treatment for chronic hepatitis C infection, they are also very costly. This produces a greater incentive to manage and monitor use to avoid prescribing in situations where they will be of no benefit. Maximizing adherence will ensure that the greatest amount of treatment benefit is achieved, and that the medications are being used in the most cost-effective manner.
Adherence to Treatment for Hepatitis CAdherence to a full course of medication treatment is largely unknown for many of the newest DAA medications. However, data from adherence to other medications for hepatitis C suggest that it may be suboptimal on average. A prior Veteran’s Administration study on rates of discontinuation for interferon/ribavirin in patients with hepatitis C infection reported that 54.9% of all patients discontinued treatment early. For the first-generation DAA boceprevir, Gordon and colleagues published an analysis of adherence in the SPRINT-2 and RESPOND-2 trials. Adherence above 80% was reported for 63% of the treated patients in one trial and 71% in the other. For patients with adherence above 80%, the sustained virologic response (SVR) was 86% and 90% in the respective trials. In contrast, for patients with adherence below 80%, rates of SVR were 8% and 32%, respectively.
The newer DAA medications, such as sofosbuvir, simeprevir, and ledipasvir, have greater efficacy, fewer adverse effects, and greater convenience than earlier agents. This would be expected to improved adherence; however, empiric data for this is lacking, particularly data on treatment in real-world settings.
Some literature on factors influencing adherence to hepatitis C treatment has been published, but most is prior to availability of DAAs. A systematic review published in 2014 analyzed 9 studies on factors influencing adherence. Two factors had a significant negative association with adherence, psychiatric disorders and higher doses of medications. In addition, female gender showed a trend toward a negative association. HIV coinfection and hemoglobin level were positively associated with adherence. Another systematic review in 2013 evaluated adherence to treatment for hepatitis B and C, prior to availability of DAAs. This review included 13 studies on hepatitis C. Mean adherence rates in these studies ranged from 27% to 97%, and the percentage of patients who had adherence rates above 80% ranged from 27% to 96%.
In addition to maximizing treatment success and cost-effectiveness, knowledge about treatment adherence can assist clinicians in managing treatment failures. Some patients will not achieve a sustained response, even with the newer agents with the greatest efficacy. In these patients, retreatment is an important consideration, and can be difficult. In deciding on retreatment, information that would indicate whether the failure is due to nonadherence or nonresponse to the medication is helpful in determining whether retreatment is indicated, and in determining which medication(s) should be used during retreatment.
Methods of Measuring AdherenceThere are various methods that can be used to monitor adherence. Patient report is the most common and efficient method, but this is the most subjective and has been shown to overestimate adherence. Pill count is another method for evaluating adherence, but is more cumbersome, and can be easily manipulated by patients. More sophisticated monitoring methods, such as sensors built into pill bottles, are expensive and usually reserved for research studies.
Measuring concentrations of medication in the serum or urine may be the most objective measure for evaluating adherence. This requires a blood or urine sample, and good benchmarks for levels that indicate optimal adherence. There is some ability to manipulate these results, ie, if correct doses are taken near the time of measurement but not at other times, but this is more difficult than with other methods.
SOF-AdhereSOF-Adhere® (Precision Toxicology, San Diego, CA) is a commercially available assay for the presence of metabolites to sofosbuvir. The test is performed on a patient’s urine sample, and uses liquid chromatography mass spectrometry to measure drug levels. It is intended for use with patients who are being treated with sofosbuvir (Sovaldi®, Harvoni®) as an aid for determining adherence.
Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests (LDTs) must meet the general regulatory standards of the Clinical Laboratory Improvement Act (CLIA). Urine metabolite tests for adherence to antiviral medications for hepatitis C are available under the auspices of CLIA. Laboratories that offer LDTs must be licensed by CLIA for high-complexity testing. To date, the U.S. Food and Drug Administration (FDA) has chosen not to require any regulatory review of these tests.
Measurement of direct-acting antiviral drug metabolite levels for the purpose of monitoring adherence to treatment for hepatitis C infection is considered investigational.
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The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
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.
11/19/2015: Approved by Medical Policy Advisory Committee.
01/15/2016: Policy reviewed; no changes.
06/07/2016: Policy number A.2.04.134 added.
08/15/2023: Medical policy number changed from "A.2.04.134" to "L.2.04.457." Policy reviewed. Policy statement unchanged.
06/26/2024: Policy reviewed; no changes.
Blue Cross Blue Shield Association policy # 2.04.134
This may not be a comprehensive list of procedure codes applicable to this policy.
Code Number | Description |
CPT-4 | |
80375 | Drug(s) or substance(s), definitive, qualitative or quantitative, not otherwise specified; 1-3 |
HCPCS | |
ICD-10 Procedure | |
ICD-10 Diagnosis |
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