TY - JOUR
T1 - Efficacy and safety of pegylated (40-kd) interferon α-2a compared with interferon α-2a in noncirrhotic patients with chronic hepatitis C
AU - Reddy, K. R.
AU - Wright, T. L.
AU - Pockros, P. J.
AU - Shiffman, M.
AU - Everson, G.
AU - Reindollar, R.
AU - Fried, M. W.
AU - Purdum, P. P.
AU - Jensen, D.
AU - Smith, C.
AU - Lee, W. M.
AU - Boyer, T. D.
AU - Lin, A.
AU - Pedder, S.
AU - DePamphilis, J.
N1 - Funding Information:
Abbreviations: IFN, interferon alfa; CHC, chronic hepatitis C; PEG(40kd) IFN α-2a, 40-kd pegylated interferon α-2a; MIU, million international units; ALT, alanine aminotransferase; HCV, hepatitis C virus; SRB, Safety Review Board; HAI, histological activity index. From the 1University of Miami School of Medicine, Miami, FL; 2VA Medical Center, San Francisco, CA; 3Scripps Clinic, La Jolla, CA; 4Medical College of Virginia, Richmond, VA; 5University of Colorado School of Medicine, Denver, CO; 6Carolinas Center for Liver Disease, Charlotte, NC; 7Emory University School of Medicine, Atlanta, GA; 8Charlotte Clinic for Gastrointestinal and Liver Disease, Charlotte, NC; 9Rush Presbyterian-St. Luke’s Medical Center, Chicago, IL; 10Minnesota Clinical Research Center, St. Paul, MN; 11Southwestern Medical Center at Dallas, Dallas, TX; 12Emory University School of Medicine, Atlanta, GA; and 13Hoffmann-La Roche Inc., Nutley, NJ. Received May 24, 2000; accepted November 9, 2000. Dr. Fried is now with the University of North Carolina, Chapel Hill, NC. Supported by a grant from F. Hoffmann-La Roche, Ltd., Basel, Switzerland. Address reprint requests to: K. Rajender Reddy, M.D., Center for Liver Diseases, 1500 NW 12th Ave., Suite 1101, Miami, FL 33136. E-mail: Rreddy@med.miami.edu; fax: 305-243-6681. Copyright © 2001 by the American Association for the Study of Liver Diseases. 0270-9139/01/3302-0016$35.00/0 doi:10.1053/jhep.2001.21747
PY - 2001/1/1
Y1 - 2001/1/1
N2 - Administration of interferon (IFN) 3 times weekly in patients with chronic hepatitis C (CHC) is associated with low sustained responses, which may be, in part, related to this regimen's inability to maintain IFN concentrations sufficient to suppress viral replication. An enhanced IFN molecule produced by the covalent attachment of a branched 40-kd polyethylene glycol moiety to IFN α-2a (PEG[40kd] IFN α-2a) exhibits sustained absorption, a restricted volume of distribution, and reduced clearance compared with unmodified IFN α-2a. One hundred fifty-nine patients with CHC participated in a randomized, ascending-dose (45 or 90, 180, 270 μg) study comparing PEG(40kd) IFN α-2a administered once weekly with 3 MIU IFN α-2a administered 3 times weekly for 48 weeks to determine the most appropriate PEG(40kd) IFN α-2a dose for subsequent clinical trials. Efficacy was assessed by measuring hepatitis C virus (HCV) RNA following a 24-week treatment-free period. Sustained virological responses for PEG(40kd) IFN α-2a once weekly were 10% (45 μg; not significant), 30% (90 μg; P = .009), 36% (180 μg; P = .0006), and 29% (270 μg; P = .004), compared with 3% for the 3-times-weekly 3-MIU IFN α-2a regimen. The types and frequencies of adverse events and laboratory abnormalities were similar among all groups. In conclusion, once-weekly PEG(40kd) IFN α-2a was associated with a higher number of sustained virological responses compared with IFN α-2a 3 times weekly in patients with CHC, but had a similar safety profile. The 180-μg PEG(40kd) IFN α-2a dose appeared to be the optimal dose based on sustained virological response and its associated side-effect profile.
AB - Administration of interferon (IFN) 3 times weekly in patients with chronic hepatitis C (CHC) is associated with low sustained responses, which may be, in part, related to this regimen's inability to maintain IFN concentrations sufficient to suppress viral replication. An enhanced IFN molecule produced by the covalent attachment of a branched 40-kd polyethylene glycol moiety to IFN α-2a (PEG[40kd] IFN α-2a) exhibits sustained absorption, a restricted volume of distribution, and reduced clearance compared with unmodified IFN α-2a. One hundred fifty-nine patients with CHC participated in a randomized, ascending-dose (45 or 90, 180, 270 μg) study comparing PEG(40kd) IFN α-2a administered once weekly with 3 MIU IFN α-2a administered 3 times weekly for 48 weeks to determine the most appropriate PEG(40kd) IFN α-2a dose for subsequent clinical trials. Efficacy was assessed by measuring hepatitis C virus (HCV) RNA following a 24-week treatment-free period. Sustained virological responses for PEG(40kd) IFN α-2a once weekly were 10% (45 μg; not significant), 30% (90 μg; P = .009), 36% (180 μg; P = .0006), and 29% (270 μg; P = .004), compared with 3% for the 3-times-weekly 3-MIU IFN α-2a regimen. The types and frequencies of adverse events and laboratory abnormalities were similar among all groups. In conclusion, once-weekly PEG(40kd) IFN α-2a was associated with a higher number of sustained virological responses compared with IFN α-2a 3 times weekly in patients with CHC, but had a similar safety profile. The 180-μg PEG(40kd) IFN α-2a dose appeared to be the optimal dose based on sustained virological response and its associated side-effect profile.
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U2 - 10.1053/jhep.2001.21747
DO - 10.1053/jhep.2001.21747
M3 - Article
C2 - 11172346
AN - SCOPUS:17744389383
SN - 0270-9139
VL - 33
SP - 433
EP - 438
JO - Hepatology
JF - Hepatology
IS - 2
ER -