title: Efficacy and safety of pegylated (40-kd) interferon alpha-2a compared with interferon alpha-2a in noncirrhotic patients with chronic hepatitis C.
abstract: 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 alpha-2a (PEG[40kd] IFN alpha-2a) exhibits sustained absorption, a restricted volume of distribution, and reduced clearance compared with unmodified IFN alpha-2a. One hundred fifty-nine patients with CHC participated in a randomized, ascending-dose (45 or 90, 180, 270 microg) study comparing PEG(40kd) IFN alpha-2a administered once weekly with 3 MIU IFN alpha-2a administered 3 times weekly for 48 weeks to determine the most appropriate PEG(40kd) IFN alpha-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 alpha-2a once weekly were 10% (45 microg; not significant), 30% (90 microg; P = .009), 36% (180 microg; P = .0006), and 29% (270 microg; P = .004), compared with 3% for the 3-times-weekly 3-MIU IFN alpha-2a regimen. The types and frequencies of adverse events and laboratory abnormalities were similar among all groups. In conclusion, once-weekly PEG(40kd) IFN alpha-2a was associated with a higher number of sustained virological responses compared with IFN alpha-2a 3 times weekly in patients with CHC, but had a similar safety profile. The 180-microg PEG(40kd) IFN alpha-2a dose appeared to be the optimal dose based on sustained virological response and its associated side-effect profile.
authors.affiliation: University of Miami School of Medicine, Miami, FL, USA. Rreddy@med.miami.edu
authors.forename: K R
authors.initials: KR
authors.lastname: Reddy
authors.forename: T L
authors.initials: TL
authors.lastname: Wright
authors.forename: P J
authors.initials: PJ
authors.lastname: Pockros
authors.forename: M
authors.initials: M
authors.lastname: Shiffman
authors.forename: G
authors.initials: G
authors.lastname: Everson
authors.forename: R
authors.initials: R
authors.lastname: Reindollar
authors.forename: M W
authors.initials: MW
authors.lastname: Fried
authors.forename: P P
authors.initials: PP
authors.lastname: Purdum
authors.forename: D
authors.initials: D
authors.lastname: Jensen
authors.forename: C
authors.initials: C
authors.lastname: Smith
authors.forename: W M
authors.initials: WM
authors.lastname: Lee
authors.forename: T D
authors.initials: TD
authors.lastname: Boyer
authors.forename: A
authors.initials: A
authors.lastname: Lin
authors.forename: S
authors.initials: S
authors.lastname: Pedder
authors.forename: J
authors.initials: J
authors.lastname: DePamphilis
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012449:Safety
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a