Treatment of chronic HCV genotype 1 infection with telaprevir: a Bayesian mixed treatment comparison of fixed-length and response-guided treatment regimens in treatment-naïve and –experienced patients

BACKGROUND Telaprevir (TVR) has been approved for response-guided-therapy (RGT) of chronic hepatitis C (HCV) genotype-1-infection in treatment-naïve and -experienced patients. In RGT-regimens patients that did not achieve extended rapid-virological-response (eRVR) within the first 4-12 weeks undergo treatment for 48-weeks, whereas in fixed-length-treatment (FLT) patients are treated for a fixed-duration regardless of their RVR. METHODS This systematic review and Bayesian mixed-treatment-comparison (MTC) aimed to compare the efficacy and safety of standard-therapy with pegylated-interferon-α/ribavirin (Peg-IFN-α/RBV (48 weeks), group A), FLT with TVR, Peg-IFN-α/RBV for 12 weeks with a long (+36 weeks, group B) or short (+12 weeks, group C) tail of Peg-IFN-α/RBV treatment, and RGT with 12 weeks of TVR, Peg-IFN-α/RBV followed by 12 weeks of Peg-IFN-α/RBV (group D) or no therapy (group E). RESULTS We identified seven randomized controlled trials including 3505 patients. Compared to standard-treatment (group A), treatment-naïve patients allocated to groups B, C, and D were significantly more likely to achieve sustained-virological-response (SVR, odds ratios (OR): B vs. A 3.5 (credibility interval [CrI] 2.2-5.4), C vs. A 3.0 (CrI 1.8-4.9), D vs. A 3.4 (CrI 2.5-4.6)). Treatment-experienced patients achieved increased SVR rates when they were treated in group B (OR: 8.2 (CrI 5.0-13.5)), C (OR 7.0 (CrI 3.9-12.8)), or simulated group D (OR 8.2 (CrI 4.3-15.3)). Patients treated with short RGT (simulated group E) did also have a significant improvement when they were treatment-experienced (simulated OR 3.6 (CrI 1.6-8.2)), whereas the effect was not significant in treatment-naïve patients (OR E vs. A 1.6 (CrI 0.9-2.7)). CONCLUSION Long FLT and RGT regimens are useful treatment options for HCV-genotype-1 in both treatment-naïve and -experienced patients. A short 24-weeks FLT regimen does not seem to be inferior and should further be evaluated in clinical trials to reduce side effects and costs of treatment.