1Department of Medicine, Division of Gastroenterology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Universita' degli Studi di Milano, Milan, Italy. Electronic address: firstname.lastname@example.org.
2AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital and University of Sydney, Sydney, Australia.
3Liver Unit, Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium.
4Outpatient Clinic to HIV and Viral Hepatitis Division of Infectious Disease, Federal University of São Paulo, São Paulo, Brazil.
5Department of Internal Medicine, First Medical Faculty, Charles University, and Central Military Hospital Prague, Prague, Czech Republic.
6Hospital Universitario 12 de Octubre, Sección de Aparato Digestivo, Madrid, Spain.
7I.M. Sechenov First Moscow State Medical University, E. M. Tareev Clinic for Nephrology, Internal and Occupational Medicine, Moscow, Russia.
8Carol Davila University of Medicine and Pharmacy, National Institute for Infectious Diseases "Prof.Dr. Matei Bals", Bucharest, Romania.
9Janssen Pharmaceutica, Beerse, Belgium.
10Janssen Pharmaceuticals, Paris, France.
11Tibotec Inc., Titusville, NJ.
12MetaVirology Ltd, London, UK.
13Medizinische Hochschule Hannover, Hannover, Germany.
BACKGROUND AND AIMS:
There is little information regarding the extent difficult to cure patients with advanced liver fibrosis due to hepatitis C virus genotype-1 (HCV-1) can successfully and safely be treated with triple therapy with telaprevir (TVR), pegylated interferon alfa (P) and ribavirin(R). In the TVR early access program HEP3002 we aimed to explore treatment safety and efficacy, and identify predictors of sustained virological response (SVR24).
PATIENTS AND METHODS:
1078 patients with bridging fibrosis (n=552) or cirrhosis (n=526) diagnosed by either liver biopsy or noninvasive markers, with compensated bone marrow (Neutrophils >1,500/mm3, Hb >12/13g/dL) and liver function (Albumin >3.3g/dL, Platelets >90,000/mL) received TVR PR for 12 weeks, followed by a PR tail according to label.
Overall, 614 (57%) achieved SVR24 by intent to treat analysis. The SVR24 rate was 68% in 221 treatment naïve patients (62.8% F4), 72% in 356 prior relapsers (64.4% F4), 55% in 139 partial responders (53.2% F4) and 34% in 294 null responders (28.6% F4). The SVR24 rate to response guided therapy (24 weeks treatment duration if undetectable viremia at weeks 4 and 12) was 84% in 222 naïve/relapser F3 patients. Independent predictors of response were: (i) F3 (Odds Ratio (OR)=1.51, 95% CI 1.31-2.00, p=0.005), (ii) Subtype 1b (OR=1.63, 95% CI 1.18-2.24, p=0.0029), (iii) Alpha-fetoprotein <10ng/mL (OR=2.50, 95% CI 1.87-3.36, p<0.0001) and (iv) any prior response other than null (OR=3.29, 95% CI 2.40-4.52, p<0.0001). SVR24 rose for patients who had more of these predictive factors: 6/32 (19%) for none, 38/139 (27%) for 1, 129/260 (50%) for 2, 202/329 (61%) for 3, and 194/235 (83%) for 4 factors. Grade 2-4 treatment-related adverse events (AE) were experienced by 719 (67%) patients; 169 (16%) discontinued therapy for AE and 7 (0.6%) died during the PR tail.
Naïve and experienced patients with advanced fibrosis or cirrhosis due to HCV-1 who have compensated bone marrow and liver function, can effectively and safely be treated by TVR triple therapy. Baseline predictors of outcome have been identified to optimize pretreatment counselling.