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

Abstract

Background & aims: 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.

Trial registration: ClinicalTrials.gov NCT01514890.

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.