title: Efficacy and safety of telaprevir, a new protease inhibitor, for difficult-to-treat patients with genotype 1 chronic hepatitis C.
abstract: The aims of this phase III study were to assess the efficacy and safety of telaprevir in combination with peginterferon alfa-2b (PEG-IFN) and ribavirin (RBV) for difficult-to-treat patients who had not achieved sustained virological response (SVR) to prior regimens in Japan. The subjects were 109 relapsers (median age of 57.0 years) and 32 nonresponders (median age of 57.5 years) with hepatitis C virus genotype 1. Patients received telaprevir (750 mg every 8 h) for 12 weeks and PEG-IFN/RBV for 24 weeks. The SVR rates for relapsers and nonresponders were 88.1% (96/109) and 34.4% (11/32), respectively. Specified dose modifications of RBV that differed from that for the standard of care were introduced to alleviate anaemia. RBV dose reductions were used for 139 of the 141 patients. The SVR rates for relapsers did not depend on RBV dose reduction for 20-100% of the planned dose (SVR rates 87.5-100%, P < 0.05). Skin disorders were observed in 82.3% (116/141). Most of the skin disorders were controllable by anti-histamine and/or steroid ointments. The ratios of discontinuation of telaprevir only or of all the study drugs because of adverse events were 21.3% (30/141) and 16.3% (23/141), respectively. A frequent adverse event leading to discontinuation was anaemia. Telaprevir in combination with PEG-IFN/RBV led to a high SVR rate for relapsers and may offer a potential new therapy for nonresponders even with a shorter treatment period.
authors.affiliation: Kansai-Rosai Hospital, Hyogo, Japan. hayashin@kanrou.net
authors.forename: N
authors.initials: N
authors.lastname: Hayashi
authors.forename: T
authors.initials: T
authors.lastname: Okanoue
authors.forename: H
authors.initials: H
authors.lastname: Tsubouchi
authors.forename: J
authors.initials: J
authors.lastname: Toyota
authors.forename: K
authors.initials: K
authors.lastname: Chayama
authors.forename: H
authors.initials: H
authors.lastname: Kumada
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D007564:Japan; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage* / Q000009:adverse effects*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects; D012871:Skin Diseases / Q000139:chemically induced; D016896:Treatment Outcome; D028761:Withholding Treatment
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009842:Oligopeptides; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C417083:peginterferon alfa-2b