Final results of a double-blind, placebo-controlled trial... : Hepatology

Original Articles

Pockros, Paul J.1*; Jeffers, Lennox2; Afdhal, Nezam3; Goodman, Zachary D.4; Nelson, David5; Gish, Robert G.6; Reddy, Rajender K.7; Reindollar, Robert8; Rodriguez-Torres, Maribel9; Sullivan, Sarah10; Blatt, Lawrence M.10; Faris-Young, Sima10

1_Division of Gastroenterology/Hepatology, Scripps Clinic, La Jolla, CA_

2_Liver Disease Center, University of Miami, Miami, FL_

3_Division of Gastroenterology, Beth Israel-Deaconess Medical Center, Boston, MA_

4_Department of Hepatic Pathology, Armed Forces Institute of Pathology, Washington, DC_

5_Division of Gastroenterology/Hepatology, University of Florida, Gainesville, FL_

6_Division of Liver Transplantation, California Pacific Medical Center, San Francisco, CA_

7_Division of Gastroenterology/Hepatology, University of Pennsylvania, Philadelphia, PA_

8_Carolinas Center for Liver Disease, Charlotte, NC_

9_Fundacion de Investigacion de Diego, Santurce, Puerto Rico_

10_Intermune Inc., Brisbane, CA_

* Address reprint requests to: Division of Gastroenterology/Hepatology, The Scripps Clinic, 10666 N. Torrey Pines Road, La Jolla, CA 92037

Email:[email protected]

Received 26 August 2005; Accepted 3 November 2006

Published online in Wiley InterScience (www.interscience.wiley.com).

Potential conflict of interest: Dr. Jeffers is on the speakers' bureau of Schering, Roche, and Bristol Myers Squibb. Dr. Nelson received grants from Intermune. Dr. Pockros is a consultant and received grants from Intermune. Dr. Reddy is an advisor for Intermune.

fax: 858-554-8065

S.F.-Y. deceased May 2006.

Abstract

Interferon-γ1b (IFN-γ1b) is a pleiotropic cytokine that displays antifibrotic, antiviral, and antiproliferative activity. A total of 502 patients with compensated liver disease and an Ishak fibrosis score of 4-6 were randomized in a double-blind, placebo-controlled study, and 488 of these patients received subcutaneous injections of IFN-γ1b 100 μg (group 1, n = 169), IFN-γ1b 200 μg (group 2, n = 157), or placebo (group 3, n = 162) 3 times a week for 48 weeks. Most patients (83.6%) had cirrhosis at baseline (Ishak score = 5 or 6). Posttreatment liver biopsies were assessed in a blinded fashion for a reduction of 1 or more Ishak points (primary endpoint). Four hundred twenty patients with pretreatment and posttreatment liver biopsies were evaluable and showed no improvement in Ishak score between the 3 treatment groups (12.1%, 12.4%, and 16% of patients in groups 1, 2, and 3, respectively; P > 0.05). Analysis of IFN-γ–inducible biomarkers revealed that interferon-inducible T cell–alpha chemoattractant (ITAC), an IFN-γ–inducible CXCR3 chemokine was an independent predictor of stable or improving Ishak score. IFN-γ1b was well tolerated. There were similar numbers of deaths in all 3 arms (5, 5, and 4, respectively), and most were related to complications of cirrhosis. Conclusion: IFN-γ1b therapy was not able to reverse fibrosis in patients with advanced liver disease for 1 year. Subgroups of patients with elevated ITAC levels and perhaps less advanced disease may be considered for future studies with IFN-γ1b. (Hepatology 2007;45:569–578.)

Abbreviations: HSC, hepatic stellate cell; IFN-γ1b, interferon-γ1b; IP, interferon-inducible protein; ITAC, interferon-inducible T cell–alpha chemoattractant; MIG, monokine induced by interferon-γ; TGF-β, transforming growth factor-β.

Final results of a double-blind, placebo-controlled trial... : Hepatology (original) (raw)

Final results of a double-blind, placebo-controlled trial of the antifibrotic efficacy of interferon-γ1b in chronic hepatitis C patients with advanced fibrosis or cirrhosis

Abstract