Background: PEG-Interferon-α and Ribavirin association is currently the standard regimen for treatment of patients suffering from HCV infection. The genotype of polymorphisms located in the IL28B (IFNL3) gene is considered a reliable predictor of response to therapy, as measured by the mean of the sustained virologic response (SVR). Aims: The purpose of the present document is to provide information about the application in the clinical practice of the pharmacogenetic test based on IL28B genotyping to guide the administration of PEG-Interferon-α-based therapy in patients with HCV infection. The use of this test within the Regional Health System was also evaluated. Economic evaluations were not considered. Methods: A focused literature review was accomplished; a systematic search was performed to identify available systematic reviews and meta-analyses. A telephone survey was performed to identify laboratories offering the IL28B pharmacogenetic test within the Regional Health System and collect current activity. Analytic validity: The genetic test is routinely based on real-time PCR allelic discrimination of the rs12979860 single nucleotide polymorphism. Despite the lack of large studies on the analytic performance, the test procedure is robust and was reported to be readily implemented in the pipeline of molecular pathology laboratories. Clinical validity: According to all the meta-analyses reviewed in the present assessment, the genotype of the IL28B rs12979860 polymorphism is a valid predictor of sustained virologic response in previously untreated patients with HCV. Carriers of the rs12979860 CC genotype show a more favourable response rate, as compared to non-CC carriers. Genotyping of other IL28B polymorphisms is not suggested. The association between response and IL28B genotypes was demonstrated for HCV genotype 1 and 4, while in genotype 2 and 3 was not definitely confirmed. The association with other endpoints, such as the rapid virologic response, was not extensively studied. Clinical utility: Though the sustained virologic response can be considered a valid measure of the clinical outcome and was widely used as endpoint in clinical studies, no evidence was found supporting the hypothesis that a regimen guided by IL28B genotyping is associated with a more favourable clinical outcome with respect to standard protocol. No clinical measure of efficacy, other than virologic response, was consistently evaluated in primary studies. Also occurrence of adverse events was not explored in association studies on IL28B genotype. Noteworthy, a multivariate model including both clinical variables and IL28B genotyping as predictors was preliminarily demonstrated to more accurately predict virologic response with respect to IL28B alone. Clinical pathways incorporating the pharmacogenetic test of IL28B were not formally evaluated in clinical trials and currently are not recommended in clinical guidelines. Ongoing studies were found in the clinical trial database. There is no literature exploring the ethical, legal and social implications of IL28B testing. However, this type of test does not raise specific concerns, provided that good practices are applied. Provision of IL28B genotyping by laboratories of the Regional Health System: The survey detected three laboratories offering pharmacogenetic IL28B testing. Approximately 550 test/year were performed in the 2012-2013 period. The ability of each laboratory to perform a larger number of test should be further estimated. It could also be considered to what extent efficiency can be improved by gathering samples in one laboratory. In addition, it should be also investigated to what extent laboratories performing few tests can guarantee a timely response, as this is a critical requisite to guarantee the proper use of the pharmacogenetic tests.
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|Titolo:||Brief HTA report: Genotipo di polimorfismi del gene dell’IL28B (IFNL3): utilizzo clinico in pazienti con HCV|
|Data di pubblicazione:||2014|
|Appare nelle tipologie:||07.12 - Altro|