title: Significant early higher ribavirin plasma concentrations in patients receiving a triple therapy with pegylated interferon, ribavirin and telaprevir.
abstract: The new standard of care for treatment for infection with genotype 1a/b of HCV now is the combination of telaprevir (TLV) with ribavirin (RBV) and pegylated interferon (Peg-IFN). Although this new therapy gives a higher response rate than the Peg-IFNα plus RBV treatment, a greatly higher rate of anaemia onset has been reported in all clinical trials. Because haemolysis is a typical concentration-dependent side effect of RBV, modulated by ITPA gene polymorphisms, we aimed to compare the early RBV plasma exposure of nine patients after 2 weeks of treatment with triple therapy with RBV concentrations of 187 patients treated with RBV and Peg-IFNα over the same time scale; this comparison was performed also stratifying patients according to ITPA polymorphism genotype and anaemia onset after 1 month of treatment. All TLV-treated patients had unfavourable ITPA genetic profile and developed anaemia. Moreover, both the rate of anaemia onset and the haemoglobin loss at 1 month were significantly higher in patients treated with TLV. This observation has been confirmed also in patients with the same ITPA genetic profile in double therapy. Strikingly, also early RBV plasma concentrations were significantly higher in patients treated with TLV. These unbiased results confirm the observations recently reported and suggest that the high rate of anaemia onset could be mainly due to the increased RBV exposure, probably caused by a 'boosting effect' by TLV. These data highlight the great importance of early therapeutic drug monitoring of RBV in the management of anaemia in the triple therapy.
authors.affiliation: Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Boglione
authors.forename: A
authors.initials: A
authors.lastname: De Nicolò
authors.forename: J
authors.initials: J
authors.lastname: Cusato
authors.forename: G
authors.initials: G
authors.lastname: Cariti
authors.forename: G
authors.initials: G
authors.lastname: Di Perri
authors.forename: A
authors.initials: A
authors.lastname: D'Avolio
mesh_terms: D000328:Adult; D000740:Anemia / Q000139:chemically induced* / Q000235:genetics; D000998:Antiviral Agents / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D011755:Pyrophosphatases / Q000235:genetics*; D012254:Ribavirin / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D016896:Treatment Outcome; D000097630:Inosine Triphosphatase
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D011092:Polyethylene Glycols; D011755:Pyrophosphatases; D012254:Ribavirin; C486464:telaprevir; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase
keywords: HCV-1; anaemia; ribavirin; telaprevir; therapeutic drug monitoring