No Impact of Insulin Resistance on Antiviral Efficacy of Telaprevir-based regimen in HCV Genotype 1 Treatment-Naive Patients: Subanalysis of C208 Study

Abstract

Insulin resistance is a predictor of poor response with peginterferon and ribavirin (PEG-IFN/RBV; PR) in chronic hepatitis C (CHC) genotype 1 (G1) patients(pts).Objective of this exploratory analysis was to assess the impact of metabolic factors and insulin resistance by HOMA index on virologic response in European CHC G1 patients treated with telaprevir (T). Methods: 161 G1 pts, randomized into 4 arms, received 12 weeks of T 750mg q8h with PEG-IFN-alfa-2a/RBV (1000 or 1200mg/day) or PEG-IFN-alfa-2b/RBV (800–1200mg/day) or T 1125mg q12h with PEG-IFN-alfa-2a/RBV or PEG-IFN-alfa-2b/RBV. Subsequently, pts received 12 or 36 weeks of additional PR based on on-treatment response criteria. Multiple regression analysis was used to explore the prognostic significance of baseline (BL) HOMA and other factors on virologic response at W4, W12, end of treatment (EOT) and 24 weeks after EOT (FU24). Results: Of 161 pts randomized, 147 had BL HOMA (mean age 44 yrs, 50% male, 91% caucasian, 24% bridging fibrosis/cirrhosis, 81% with viral load >800.000IU/mL, mean BMI 25, 3.4% with diabetes, 12.0% with hypertension). Proportion of pts with HOMA <2 was 55.8%; 2–4: 31.3% and >4: 12.9%. Independent factors correlated with BL HOMA were BMI (OR=1.31) and viral load (OR=2.00). In ITT analysis, sustained virologic response (SVR) was similar across the 4 treatment arms (81–85%). Neither response rates at W4, W12, EOT and FU24 nor viral load decline at W4 were significantly influenced by BL HOMA (figure). In multivariate analysis only fibrosis stage was predictive of SVR (OR=0.58, 95% CI: 0.35, 0.97). At FU24, HOMA was significantly lower in SVR patients compared to non SVR (p<0.05). Conclusions: In this retrospective analysis of G1 pts treated with T based regimen BL HOMA was not predictive of virologic response. SVR was associated with an improvement of HOMA. Metabolic factors and insulin resistance might not have significant impact on treatment efficacy. Further confirmation is warranted.