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SUSTAINED VIROLOGIC RESPONSE RATES AND VIRAL RESISTANCE PROFILES IN PATIENTS TREATED WITH A TELAPREVIR-BASED REGIMEN REGARDLESS OF LIVER FIBROSIS STAGE
A Di Bisceglie1, P Marcellin2, J Sullivan3, M Fried4, T Kieffer3, G Dusheiko5, E Martin3, D Nelson6, C Wright3, S George3, L Bengtsson3, D Bartels3, G Everson7, N Adda31Saint Louis University School of Medicine, Saint Louis, Missouri, USA; 2University of Paris Clichy, Clichy, France; 3Vertex Pharmaceuticals Incorporated, Cambridge, Massachusetts; 4University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; 5Royal Free and University College, London, United Kingdom; 6University of Florida, Gainesville, Florida; 7University of Colorado Denver, Aurora, Colorado, USA
Aims: ADVANCE and ILLUMINATE were Phase 3 randomized studies that evaluated the safety and efficacy of telaprevir (T) in combination with PR in treatment-naive genotype 1 HCV patients. In this pooled analysis of ADVANCE patients and ILLUMINATE patients (T12PR N=903, PR N=361), we evaluated the effects of liver fibrosis stage on response to treatment and occurrence of telaprevir-resistant variants.
Methods: We compared the virologic response rates of T12PR therapy (ADVANCE/ILLUMINATE) and PR therapy (ADVANCE) between patients with no/minimal or portal fibrosis (F0-F2) and patients with bridging fibrosis or cirrhosis (F3-F4). In patients treated with T12PR who failed to achieve a sustained virologic response (SVR), the presence of low- or high-level resistant variants, determined by viral population sequencing, was analyzed by pretreatment fibrosis stage.
Results: Efficacy outcomes after T/PR treatment were improved over PR, regardless of fibrosis stage (see table). In patients who failed to achieve SVR and had sequence data available (n=156), resistant variants occurred at similar rates and with similar resistance phenotypes between fibrosis stages (low-level: 38% in F0-F2, 43% in F3-F4; high-level: 38% in F0-F2, 44% in F3-F4). In patients with detectable resistant variants after failure and with follow-up sequence data available (n=105), median time-to-loss of resistant variants was 9 months in F0-F2 and 10 months in F3-F4.
Conclusions: Telaprevir-based therapy improved SVR rates compared to PR alone regardless of liver fibrosis stage (+29%, F0-F2; +30%, F3-F4). Within a treatment group, virologic failure and relapse rates were higher in patients with bridging fibrosis or cirrhosis than in those with no/minimal or portal fibrosis. T12PR patients who failed to achieve SVR had similar resistance profiles and median time-to-loss of resistant variants, regardless of the pre-treatment liver disease stage.