title: Triple therapy in treatment-experienced patients with HCV-cirrhosis in a multicentre cohort of the French Early Access Programme (ANRS CO20-CUPIC) - NCT01514890.
abstract: OBJECTIVE
  In phase III trials, the safety profile of triple therapy (pegylated interferon/ribavirin with boceprevir or telaprevir) seems to be similar in HCV treatment-experienced cirrhotic and non-cirrhotic patients, but few cirrhotics were included. We report the week 16 safety and efficacy analysis in a cohort of compensated cirrhotics treated in the French Early Access Programme.
  
  
  METHODS
  674 genotype 1 patients, prospectively included, received 48 weeks of triple therapy. The analysis is restricted to 497 patients reaching week 16.
  
  
  RESULTS
  A high incidence of serious adverse events (40.0%), and of death and severe complications (severe infection or hepatic decompensation) (6.4%), and a difficult management of anaemia (erythropoietin and transfusion use in 50.7% and 12.1%) were observed. Independent predictors of anaemia < 8 g/dl or blood transfusion were: female gender (OR 2.19, 95% CI 1.11-4.33, p=0.024), no lead-in phase (OR 2.25, 95% CI 1.15-4.39, p=0.018), age ≥ 65 years (OR 3.04, 95% CI 1.54-6.02, p=0.0014), haemoglobin level (≤ 12 g/dl for females, ≤ 13 g/dl for males) (OR 5.30, 95% CI 2.49-11.5, p=0.0001). Death or severe complications were related to platelets count ≤ 100,000/mm(3) (OR 3.11, 95% CI 1.30-7.41, p=0.0105) and albumin <35 g/dl (OR 6.33, 95% CI 2.66-15.07, p=0.0001), with a risk of 44.1% in patients with both. However, the on-treatment virological response was high.
  
  
  CONCLUSIONS
  The safety profile was poor and patients with platelet count ≤ 100,000/mm(3) and serum albumin <35 g/L should not be treated with the triple therapy.
authors.affiliation: Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, AP-HP, Université Paris-Est, INSERM U955, Créteil, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Hézode
authors.forename: Hélène
authors.initials: H
authors.lastname: Fontaine
authors.forename: Céline
authors.initials: C
authors.lastname: Dorival
authors.forename: Dominique
authors.initials: D
authors.lastname: Larrey
authors.forename: Fabien
authors.initials: F
authors.lastname: Zoulim
authors.forename: Valérie
authors.initials: V
authors.lastname: Canva
authors.forename: Victor
authors.initials: V
authors.lastname: de Ledinghen
authors.forename: Thierry
authors.initials: T
authors.lastname: Poynard
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
authors.forename: Marc
authors.initials: M
authors.lastname: Bourlière
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Zarski
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Raabe
authors.forename: Laurent
authors.initials: L
authors.lastname: Alric
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.forename: Ghassan
authors.initials: G
authors.lastname: Riachi
authors.forename: Pierre-Henri
authors.initials: PH
authors.lastname: Bernard
authors.forename: Véronique
authors.initials: V
authors.lastname: Loustaud-Ratti
authors.forename: Sophie
authors.initials: S
authors.lastname: Métivier
authors.forename: Albert
authors.initials: A
authors.lastname: Tran
authors.forename: Lawrence
authors.initials: L
authors.lastname: Serfaty
authors.forename: Armand
authors.initials: A
authors.lastname: Abergel
authors.forename: Xavier
authors.initials: X
authors.lastname: Causse
authors.forename: Vincent
authors.initials: V
authors.lastname: Di Martino
authors.forename: Dominique
authors.initials: D
authors.lastname: Guyader
authors.forename: Damien
authors.initials: D
authors.lastname: Lucidarme
authors.forename: Véronique
authors.initials: V
authors.lastname: Grando-Lemaire
authors.forename: Patrick
authors.initials: P
authors.lastname: Hillon
authors.forename: Cyrille
authors.initials: C
authors.lastname: Feray
authors.forename: Thong
authors.initials: T
authors.lastname: Dao
authors.forename: Patrice
authors.initials: P
authors.lastname: Cacoub
authors.forename: Isabelle
authors.initials: I
authors.lastname: Rosa
authors.forename: Pierre
authors.initials: P
authors.lastname: Attali
authors.forename: Ventzislava
authors.initials: V
authors.lastname: Petrov-Sanchez
authors.forename: Yoann
authors.initials: Y
authors.lastname: Barthe
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Pawlotsky
authors.forename: Stanislas
authors.initials: S
authors.lastname: Pol
authors.forename: Fabrice
authors.initials: F
authors.lastname: Carrat
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bronowicki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D005602:France; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage* / Q000009:adverse effects; D011392:Proline / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D011446:Prospective Studies; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; D012254:Ribavirin; C486464:telaprevir; 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
keywords: AFEF; ALT; ANRS; ATU; Association Française pour l’Etude du Foie; BOC; Boceprevir; CUPIC; Chronic hepatitis C; Cirrhosis; EPO; HBV; HCV; HIV; PI; PegIFN; RBV; SAE; SCAR; SD; SVR; Safety; TVR; Telaprevir; Treatment; agence nationale de recherches sur le SIDA et les hépatites virales; alanine aminotransferase; autorisation temporaire d’utilisation; boceprevir; compassionate use of protease inhibitors in viral C cirrhosis; erythropoietin; hepatitis B virus; hepatitis C virus; human immunodeficiency virus; pegylated interferon; protease inhibitor; ribavirin; serious adverse event; severe cutaneous adverse reaction; standard deviation; sustained virological response; telaprevir