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P48 Telaprevir substantially improved SVR rates across all IL28B genotypes in the advance trial
  1. G M Dusheiko1,
  2. I M Jacobson2,
  3. I Catlett3,
  4. S George3,
  5. S Seepersaud3,
  6. R Ramachandran3,
  7. K Sussky3,
  8. R S Kauffman3,
  9. M Botfield3
  1. 1Royal Free and University College, London, UK
  2. 2Weill Cornell Medical College, New York, New York, USA
  3. 3Vertex Pharmaceuticals Incorporated, Cambridge, Massachusetts, USA

Abstract

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.

Abstract P48 Table 1

SVR rates

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