- Category: HCV Treatment
- Published on Tuesday, 15 November 2011 00:00
- Written by Liz Highleyman
Adding telaprevir to pegylated interferon/ribavirin increased the likelihood of a cure for genotype 1 chronic hepatitis C patients with liver cirrhosis in the REALIZE trial, according to data presented at the American Association for the Study of Liver Diseases Liver Meeting (AASLD 2011) last week in San Francisco.
The advent of hepatitis C virus (HCV) direct-acting antiviral agents has revolutionized treatment, but drugs such as the recently approved HCV protease inhibitors telaprevir (Incivek) and boceprevir (Victrelis) have not yet been well studied in people with advanced liver disease -- a group that responds poorly to standard interferon-based therapy.
Stanislas Pol from Université Paris Descartes and colleagues performed a sub-analysis to assess the safety and efficacy of telaprevir plus pegylated interferon/ribavirin among prior non-responders with Child A stage cirrhosis in the pivotal REALIZE trial.
REALIZE compared 2 telaprevir regimens -- 12 weeks of telaprevir/pegylated interferon/ribavirin triple therapy followed by 36 weeks of pegylated interferon/ribavirin alone, or a 4-week pegylated interferon/ribavirin lead-in followed by 12 weeks of triple therapy and 32 weeks of pegylated interferon/ribavirin alone -- versus pegylated interferon/ribavirin standard therapy for 48 weeks.
Out of the total 662 participants in the trial, 578 had complete information about liver disease status at baseline; within this group, 143 patients had liver cirrhosis (fibrosis stage F4). The majority of participants were men and almost all were white. People with cirrhosis were slightly older than non-cirrhotics (54 vs 50 years) and were more likely to be prior null responders rather than partial responders or relapsers (36% vs 25%). Patients taking the 2 different telaprevir regimens were pooled.
- Overall, participants who received telaprevir triple had significantly higher sustained virological response (SVR) rates than those who received pegylated interferon/ribavirin standard therapy alone.
The benefit of adding telaprevir was seen across all fibrosis stages:
- Cirrhosis (stage F4): SVR 47% with telaprevir triple therapy vs 8% with pegylated interferon/ribavirin alone;
- Bridging fibrosis (stage F3): 67% vs 7%, respectively;
- Absent, minimal, or moderate fibrosis (stage F0-F2): 75% vs 22%, respectively.
The benefit of adding telaprevir was greatest for patients with better prior response and not appreciably different for null responders:
- Prior relapsers: SVR 84% with telaprevir triple therapy vs 7% with pegylated interferon/ribavirin alone;
- Prior partial responders: 34% vs 20%, respectively;
- Prior null responders: 14% vs 10%, respectively.
Looking only at telaprevir recipients, prior null and partial responders with cirrhosis had lower SVR rates than non-cirrhotics, but prior relapsers were similar:
- Prior relapsers: SVR 84% for cirrhotics vs 87% for absent-to-moderate fibrosis;
- Prior partial responders: 34% vs 77%, respectively;
- Prior null responders: 14% vs 41%, respectively.
- 32% of patients with cirrhosis experienced on-treatment virological failure, compared with 13% of non-cirrhotics.
- 12% and 5%, respectively, relapsed after completing therapy.
- In a multivariate analysis of patients with cirrhosis, baseline ALT or AST and degree of prior response were significant predictors of response.
- Among patients who experienced virological failure on telaprevir, there was no association between telaprevir resistance and fibrosis/cirrhosis stage.
- Among patients with cirrhosis, side effects that occurred more often in the telaprevir arms than in the standard therapy arm included skin rash, pruritis (itching), and anemia.
- 15% of patients with cirrhosis and 12% of non-cirrhotic patients discontinued telaprevir due to adverse events.
"Telaprevir plus [pegylated interferon/ribavirin] resulted in higher SVR rates in treatment-experienced patients with cirrhosis compared with [pegylated interferon/ribavirin] alone," the researchers concluded. "Rates of discontinuation due to [adverse events] were slightly higher in cirrhotic versus non-cirrhotic patients."
Investigator affiliations: Université Paris Descartes, INSERM Unité 1016, and Assistance Publique-Hôpitaux de Paris, Cochin Hospital, Paris, France; Department of Gastroenterology, Alfred Hospital, Melbourne, VIC, Australia; Università di Bologna, Bologna, Italy; Center for Liver Diseases and Department of Medicine, Inova Fairfax Hospital, Falls Church, VA; Hospital General de Valencia, Valencia, Spain; Alamo Medical Research, San Antonio, TX; Emilio Ribas Infectious Diseases Institute, São Paulo, Brazil; Queen Marys University of London, Institute of Cell and Molecular Science, London, UK; Medical University of Warsaw, Warsaw, Poland; Janssen Pharmaceuticals, Paris, France; Tibotec Inc., Titusville, NJ; Tibotec BVBA, Beerse, Belgium; Johann Wolfgang Goethe University Medical Center, Frankfurt am Main, Germany.
S Pol, SK Roberts, P Andreone, et al. Efficacy and safety of telaprevir-based regimens in cirrhotic patients with HCV genotype 1 and prior peginterferon/ribavirin treatment failure: subanalysis of the REALIZE Phase III study. 62nd Annual Meeting of the American Association for the Study of Liver Disease (AASLD 2011). San Francisco, November 4-8. 2011. Abstract 31.