Aim Single nucleotide polymorphisms (SNPs) near the IL28B gene region have been strongly associated with the likelihood of SVR in genotype 1 HCV patients treated with peginterferon/ribavirin (PR). During the evaluation of an exploratory diagnostic test that characterises genetic polymorphisms near the IL28B gene, the impact of rs1297860 on SVR in telaprevir (T)-based regimens in the ADVANCE trial was evaluated.
Method IL28B genotype testing was performed according to a US FDA guidance governing use of de-identified leftover samples for in vitro diagnostic testing. The guidance requires a strict de-identification procedure that was carried out by an independent third party. Only specimens from the USA were used; and as non-Caucasian patients could not be de-identified in sufficient numbers, they were excluded from the study.
Results The diagnostic assay developed provided consistent, unambiguous genotype calls and was considered suitable for research. 454/1088 (42%) patients had IL28B test results available. 150/454 (33%) were CC, 224/454 (49%) CT, and 80/454 (18%) TT. SVR rates for each subgroup by arm are shown in the Abstract P48 table 1. 72%, 54% and 48% of CC, CT and TT telaprevir patients, respectively had undetectable HCV RNA at weeks 4 and 12 (eRVR) compared with 16%, 2% and 0% of PR patients. Among eRVR telaprevir patients, 91% achieved SVR (97% of CC, 88% of CT, 85% of TT) with 24 weeks of therapy whereas 43% of non-eRVR telaprevir patients had SVR (63% of CC, 33% of CT, 46% of TT) with 48 weeks of therapy.
Conclusion Telaprevir-based therapy improved eRVR and SVR rates across all IL28B genotypes. Specifically, telaprevir-based therapy more than doubled the rates of SVR in CT/TT patients, and substantially increased SVR rates in those with CC genotype, as compared with PR therapy alone. Non-attainment of eRVR was associated with lower SVR rates across all IL28B genotypes, with the largest decrement in CT/TT patients.
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