title: Safety and efficacy of triple therapy with peginterferon, ribavirin and boceprevir within an early access programme in Spanish patients with hepatitis C genotype 1 with severe fibrosis: SVRw12 analysis.
abstract: OBJECTIVE
  The addition of protease inhibitors (PIs) changed the hepatitis C virus (HCV) treatment standards and improved sustained viral response (SVR) rates in patients with genotype 1 HCV infection.
  
  
  METHODS
  Prospective, multicentre, national registry that includes naïve and treatment-experienced patients with HCV genotype 1 infection, who had bridging fibrosis or cirrhosis and were treated with triple therapy (peginterferon alfa-2a or alfa-2b, ribavirin and boceprevir) as compassionate use, and in accordance with the Summary of Product Characteristics.
  
  
  RESULTS
  Most of the patients (68.2%) were male, with a mean age of 53 years, 75% (n = 128) had HCV 1b genotype and baseline viral load of 6.2 log. According to prior treatment, 20% of patients were treatment-naïve and 80% had received prior treatment. Approximately 36.5% of patients (n = 62) reported at least one serious adverse events (SAEs) (total SAEs = 103). The most common SAEs were neutropenia (57.6%), anaemia (47.6%) and grade 3 thrombopenia (25.9%). Patients with albumin <3.5 g/dl and bilirubin >2 mg/dl had an increased relative risk (greater than one-fold) for SAEs, including infections and hepatic decompensation. In the intent-to-treat analysis (n = 170), the overall percentage of patients with SVRw12 was 46.5%. In patients with 1 log decrease at week 4 (lead-in phase), the overall SVRw12 rate was 67.0%. In the patients initiating triple therapy with boceprevir (n = 139), the global response rate was 56.4%. In a multivariate analysis, an increased probability of achieving SVR was associated with response to prior treatment (relapsers), >1 log decrease in viral load in the lead-in phase and baseline albumin >3.5 g/dl.
  
  
  CONCLUSIONS
  Triple therapy in patients with severe fibrosis/cirrhosis is associated with a higher rate of SAE and a lower rate in comparison with patients with mild disease. However, for patients with intact liver function, it could be considered as a treatment option, when other alternatives would not be available.
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital Puerta de Hierro Majadahonda, IDIPHIM and CIBEREHD, Madrid, Spain.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Calleja
authors.forename: Juan M
authors.initials: JM
authors.lastname: Pascasio
authors.forename: Belén
authors.initials: B
authors.lastname: Ruiz-Antorán
authors.forename: Francisco
authors.initials: F
authors.lastname: Gea
authors.forename: Rafael
authors.initials: R
authors.lastname: Bárcena
authors.forename: Juan R
authors.initials: JR
authors.lastname: Larrubia
authors.forename: Ramón
authors.initials: R
authors.lastname: Pérez-Álvarez
authors.forename: Jose M
authors.initials: JM
authors.lastname: Sousa
authors.forename: Manuel
authors.initials: M
authors.lastname: Romero-Gómez
authors.forename: Ricard
authors.initials: R
authors.lastname: Solá
authors.forename: Juan
authors.initials: J
authors.lastname: de la Revilla
authors.forename: Javier
authors.initials: J
authors.lastname: Crespo
authors.forename: Jose M
authors.initials: JM
authors.lastname: Navarro
authors.forename: Juan I
authors.initials: JI
authors.lastname: Arenas
authors.forename: Manuel
authors.initials: M
authors.lastname: Delgado
authors.forename: Conrado M
authors.initials: CM
authors.lastname: Fernández-Rodríguez
authors.forename: Ramon
authors.initials: R
authors.lastname: Planas
authors.forename: Maria
authors.initials: M
authors.lastname: Buti
authors.forename: Xavier
authors.initials: X
authors.lastname: Forns
mesh_terms: D057176:Compassionate Use Trials; D004359:Drug Therapy, Combination / Q000009:adverse effects; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D011392:Proline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D013030:Spain
chemical_list: D016898:Interferon-alpha; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline; C100416:peginterferon alfa-2a
keywords: boceprevir; compassionate use; hepatitis C; safety and efficacy; severe fibrosis