title: Daclatasvir/peginterferon lambda-1a/ribavirin in patients with chronic HCV infection and haemophilia who are treatment naïve or prior relapsers to peginterferon alfa-2a/ribavirin.
abstract: OBJECTIVE
  This study explores the potential role of a novel interferon-containing regimen for treatment of patients with chronic hepatitis C (CHC) and underlying haemophilia.
  
  
  METHODS
  This trial (NCT01741545) was an open-label, non-randomized phase 3 study, which included adult haemophiliacs with hepatitis C virus (HCV). Patients with HCV genotypes (GT)-2 or -3 were treated with Lambda-IFN/ribavirin (RBV)/daclatasvir (DCV) for 12 weeks (cohort A). Patients with HCV GT-1b or -4 were treated with Lambda-IFN/RBV/DCV for 12 weeks, followed by Lambda-IFN/RBV for an additional 12 weeks (cohort B). The primary endpoint was the proportion of patients with a sustained virologic response at post-treatment follow-up week 12 (SVR12). Clinical development of Lambda-IFN was discontinued during this trial leading to study termination before a 24-week post-treatment follow-up was obtained for all participants.
  
  
  RESULTS
  Overall, 51 patients were treated (cohort A, n = 12; cohort B, n = 39). The proportion of patients achieving SVR12 was 92% in cohort A and 90% in cohort B. Therapy was generally well tolerated. The most common adverse events (AEs) were related to elevations in serum transaminases and/or bilirubin. Five serious AEs, four discontinuations due to AEs, and no deaths were reported. The rate of grade 3-4 bilirubin elevations was 17-18% across cohorts.
  
  
  CONCLUSIONS
  Lambda-IFN/RBV/DCV treatment demonstrated a high SVR rate and was generally well tolerated with a safety profile consistent with expectations for this special patient population. This study supports use of DCV as part of a combination treatment regimen for haemophiliacs with CHC.
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Ca' Granda Foundation, Maggiore Hospital Policlinico, Milan, Italy. elena.santagostino@policlinico.mi.it.
authors.forename: E
authors.initials: E
authors.lastname: Santagostino
authors.affiliation: Hôpital Cochin, Université Paris Descartes, Inserm U-818, Institut Pasteur, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Pol
authors.affiliation: Hospital Universitario La Paz, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Olveira
authors.affiliation: Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: H W
authors.initials: HW
authors.lastname: Reesink
authors.affiliation: Universitair Medisch Centrum Utrecht, Utrecht, the Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: van Erpecum
authors.affiliation: Clinical Hospital of Tsentrosoyuz, Moscow, Russia.
authors.forename: P
authors.initials: P
authors.lastname: Bogomolov
authors.affiliation: Bristol-Myers Squibb, Inc., Wallingford, CT, USA.
authors.forename: D
authors.initials: D
authors.lastname: Xu
authors.affiliation: Bristol-Myers Squibb, Inc., Wallingford, CT, USA.
authors.forename: L
authors.initials: L
authors.lastname: Critelli
authors.affiliation: Bristol-Myers Squibb, Inc., Wallingford, CT, USA.
authors.forename: S
authors.initials: S
authors.lastname: Srinivasan
authors.affiliation: Bristol-Myers Squibb, Inc., Wallingford, CT, USA.
authors.forename: E
authors.initials: E
authors.lastname: Cooney
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002219:Carbamates; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005838:Genotype; D006467:Hemophilia A / Q000150:complications* / Q000175:diagnosis; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000009:adverse effects / Q000235:genetics / Q000627:therapeutic use*; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D011759:Pyrrolidines; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011759:Pyrrolidines; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; D014633:Valine; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C000600496:peginterferon lambda-1a; C549273:daclatasvir; C100416:peginterferon alfa-2a
keywords: daclatasvir; haemophilia; hepatitis C; peginterferon lambda-1a; ribavirin; sustained virologic response