PMO-166 Early experience with telaprevir for patients with advanced fibrosis or cirrhosis

Introduction The direct-acting HCV protease inhibitor telaprevir has recently been licensed for treatment of chronic genotype 1 HCV infection, and promises significant improvements in sustained virological response for these patients. However the patients who may benefit most from novel HCV therapies, namely those with advanced fibrosis or cirrhosis who have previously failed to respond to pegylated interferon (pegIFN) and ribavirin treatment, are relatively poorly represented in the telaprevir clinical trials. Efficacy, safety and tolerability were assessed in patients with genotype 1 HCV and advanced fibrosis/cirrhosis who have received telaprevir-containing treatment at the Royal London Hospital. Methods Laboratory results and case notes were reviewed for all patients treated with pegIFN, ribavirin and telaprevir at the Royal London Hospital between September 2011 and January 2012. Results Eight patients with genotype 1 HCV had commenced telaprevir-containing treatment. All had advanced fibrosis/cirrhosis (median Ishak score 5, range 4–6). One was treatment-naive, three had previously failed to respond to pegIFN/ribavirin and four had relapsed after therapy. All patients had completed at least 4 weeks of telaprevir-containing therapy. With one exception, all patients achieved undetectable HCV RNA at week 4 of treatment; the patient who did not had a viral load of 168 IU/ml at week 4 and undetectable HCV RNA at week 8. One patient had completed 12 weeks of therapy, with undetectable HCV RNA. The most common side effects were fatigue (8/8), pruritis (4/8), rash (3/8), anal pain (3/8), depression (3/8), nausea (3/8), gastrointestinal disturbance (2/8) and oral candidiasis (2/8). Most side effects were successfully managed, although telaprevir was stopped in two patients at week 8 due to worsening rash and one patient withdrew from all therapy at week 4 due to tolerability. The most common laboratory abnormality was an early, transient rise in bilirubin (3/8). Significant anaemia (Hb). Conclusion Telaprevir in combination with pegIFN and ribavirin appears efficacious in patients with advanced fibrosis or cirrhosis, who have previously failed treatment with pegIFN and ribavirin alone. However, the incidence of significant side effects in this subgroup of patients is high and necessitates frequent follow-up with medical support. Side effects, particularly rash, may limit duration of telaprevir treatment. Whether this impacts on sustained virological response remains to be seen. Competing interests M Cunningham: None declared, J Schulz: None declared, L Payaniandy: None declared, Y Kallis: None declared, P Kennedy: None declared, P Kooner: None declared, R Marley: None declared, G Foster grant/research Support from: Roche, Janssen, Tibotec, Novartis, Consultant for: Abbott, BI, BMS, Chughai, Janssen, Merck, Novartis, Roche, Tibotec.