Purpose: Phase 3 trials have shown improved efficacy with protease inhibitor based triple therapy in treating chronic hepatitis C (CHC). The aim of this study is to examine the on-treatment effectiveness and tolerability of triple therapy with peginterferon, ribavirin and telaprevir in CHC patients treated in a real life academic hepatology practice setting.
Methods: A prospective database tracking all viral hepatitis patients undergoing antiviral therapy was queried to identify CHC patients treated with a telaprevir-containing regimen outside clinical trials. Both treatment-naïve and -experienced adult patients were included while those with co-infection with HIV or HBV were excluded. In performing an intent to treat analysis, on-treatment response categories included (1) rapid virologic response (RVR: negative HCV RNA at week 4); (2) extended rapid virologic response (eRVR: negative HCV RNA at weeks 4 and 12); and (3) Early virologic response (EVR: negative HCV RNA at week 12). Responses up to week 24 are reported at the present time.
Results: There were 55 patients analyzed who met the eligibility criteria, consisting of treatment-naïve (n=35) and-experienced (n=20, relapse=13 and non-response=7). All the patients were infected with HCV genotype 1 except 2 patients who had HCV genotype 4. There were a total of 8 patients whose treatment was terminated early for intolerance. Intolerance included anemia (n=2), neuropathy (n=2), nausea/vomiting (n=2), rash (n=1) and dizziness (n=1). Table shows proportions of RNA negative at the specified time intervals by the intent to treat analysis. Of week 12 responders (73%), 40% had eRVR and the remaining 33% achieved RNA-negative for the first time at week 12. eRVR occurred in 30% of naïve patients and 44% of treatment experienced. The average drop in hemoglobin in weeks 4, 8 and 24 of treatment were 3 mg/dl, 3.5 mg/dl and 3 mg/dl, respectively, compared to the pre-treatment levels by per protocol analysis.
Conclusion: On-treatment response to telaprevir-based triple therapy in real life practice is substantially lower than that reported in registration trials (e.g., eRVR in naïve patients=58-65%), heralding a lower SVR than anticipated. Even with ribavirin dose reduction and erythropoietin support, significant degree of anemia complicates therapy.