Triple therapy in treatment-experienced patients with HCV-cirrhosis in a multicentre cohort of the French Early Access Programme (ANRS CO20-CUPIC) – NCT01514890

Christophe Hézode (1) , Hélène Fontaine (2) , Céline Dorival (3) , Dominique Larrey (4) , Fabien Zoulim (5) , Valérie Canva (6) , Victor de Ledinghen (7, 8) , Thierry Poynard (9, 10) , Didier Samuel (11) , Marc Bourlière (12) , Jean-Pierre Zarski (13) , Jean-Jacques Raabe (14) , Laurent Alric (15) , Patrick Marcellin (16, 17) , Ghassan Riachi (18) , Pierre Paul Bernard (7, 8) , Véronique Loustaud-Ratti (19, 20) , Sophie Métivier (21) , Albert Tran (22) , Lawrence Serfaty (23) , Armand Abergel (24, 25) , Xavier Causse (26) , Vincent Di Martino (27) , Dominique Guyader (28) , Damien Lucidarme (29) , Véronique Grando-Lemaire (30) , Patrick Hillon (31) , Cyrille Feray (32) , Thong Dao (33) , Patrice Cacoub (9, 34) , Isabelle Rosa (35) , Pierre Attali (36) , Ventzislava Petrov-Sanchez (37) , Yoann Barthe (3) , Jean-Michel Pawlotsky (1, 38) , Stanislas Pol (2) , Fabrice Carrat (3, 23) , Jean-Pierre Bronowicki (39, 40)

1 IMRB - Institut Mondor de Recherche Biomédicale
2 IC UM3 (UMR 8104 / U1016) - Institut Cochin
3 DS3 - ESIM - Déterminants Sociaux de la Santé et du Recours aux Soins
4 Institut de recherche en biothérapie
5 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
6 Service d'Hépato-gastroentérologie [CHU Lille]
7 Physiopathologie du cancer du foie
8 Département d'hépatologie et de gastroentérologie [CHU Bordeaux]
9 CHU Pitié-Salpêtrière [AP-HP]
10 Pathologies biliaires, fibrose et cancer du foie
11 CHB - Centre hépato-biliaire
12 Service d'hépato-gastro-entérologie
13 INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble
14 Service d'Hépato-gastro-entérologie [CHR Metz-Thionville]
15 PHARMA-DEV - Pharmacochimie et Biologie pour le Développement
16 Service d'hépatologie
17 CRB3 - Centre de recherche biomédicale Bichat-Beaujon
18 Service d'Hépato-Gastroentérologie [CHU Rouen]
19 RESINFIT - Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques
20 Service d'Hépato-gastro-entérologie et Nutrition [CHU Dupuytren 1, Limoges]
21 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
22 C3M - Centre méditerranéen de médecine moléculaire
23 CHU Saint-Antoine [AP-HP]
24 Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand]
25 ISIT - Image Science for Interventional Techniques
26 Service d’Hépato-Gastro-Entérologie [Orléans]
27 Service d'Hépatologie [CHRU Besançon]
28 Foie, métabolismes et cancer
29 Service d'hépato-gastro-entérologie
30 Service d'hépato-gastro-entérologie
31 Service d'Hépato-Gastro-Entérologie (CHU de Dijon)
32 Service Hépato-gastroentérologie [Nantes]
33 Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen]
34 I3 - Immunologie - Immunopathologie - Immunothérapie
35 Service d'hépato-gastro-entérologie
36 Service d'Hépato-gastro-entérologie [APHP Kremlin-Bicêtre]
37 Recherches fondamentales, cliniques et thérapeutiques sur les hépatites virales
38 Service de bactériologie, virologie, hygiène [Mondor]
39 Service d'Hépato-gastro-entérologie [CHRU Nancy]
40 NGERE - Nutrition-Génétique et Exposition aux Risques Environnementaux

Background & AimsIn 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.Methods674 genotype 1 patients, prospectively included, received 48 weeks of triple therapy. The analysis is restricted to 497 patients reaching week 16.ResultsA 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/mm3 (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.ConclusionsThe safety profile was poor and patients with platelet count ⩽100,000/mm3 and serum albumin <35 g/L should not be treated with the triple therapy.

Mots clés: Chronic hepatitis C; Cirrhosis; Treatment; Boceprevir; Telaprevir; Safety

Domaines: Sciences du Vivant [q-bio]

Christophe Hézode, Hélène Fontaine, Céline Dorival, Dominique Larrey, Fabien Zoulim, et al.. Triple therapy in treatment-experienced patients with HCV-cirrhosis in a multicentre cohort of the French Early Access Programme (ANRS CO20-CUPIC) – NCT01514890. Journal of Hepatology, 2013, 59 (3), pp.434 - 441. ⟨10.1016/j.jhep.2013.04.035⟩. ⟨hal-01708037⟩