title: Peginterferon alpha-2a (40 kDa): an advance in the treatment of hepatitis B e antigen-positive chronic hepatitis B.
abstract: Current therapies for chronic hepatitis B (CHB) have a number of limitations, and better treatment options are needed. Peginterferon alpha-2a (40 kDa) is superior to conventional interferon alpha-2a in the treatment of chronic hepatitis C. This is the first report on peginterferon alpha-2a (40 kDa) in the treatment of CHB. In this phase II study, 194 patients with CHB not previously treated with conventional interferon-alpha were randomized to receive weekly subcutaneous doses of peginterferon alpha-2a (40 kDa) 90, 180 or 270 microg, or conventional interferon alpha-2a 4.5 MIU three times weekly. Twenty-four weeks of therapy were followed by 24 weeks of treatment-free follow-up. All subjects were assessed for loss of hepatitis B e antigen (HBeAg), presence of hepatitis B antibody (anti-HBe), suppression of hepatitis B virus (HBV) DNA, and normalization of serum alanine transaminase (ALT) after follow-up. At the end of follow-up, HBeAg was cleared in 37, 35 and 29% of patients receiving peginterferon alpha-2a (40 kDa) 90, 180 and 270 microg, respectively, compared with 25% of patients on conventional interferon alpha-2a. The combined response (HBeAg loss, HBV DNA suppression, and ALT normalization) of all peginterferon alpha-2a (40 kDa) doses combined was twice that achieved with conventional interferon alpha-2a (24%vs 12%; P = 0.036). All treatment groups were similar with respect to frequency and severity of adverse events. These results indicate that peginterferon alpha-2a (40 kDa) is superior in efficacy to conventional interferon alpha-2a in chronic hepatitis B based on clearance of HBeAg, suppression of HBV DNA, and normalization of ALT.
authors.affiliation: Royal Brisbane Hospital, Herston, Queensland, Australia. grahamc@qimr.edu.au
authors.forename: W G E
authors.initials: WG
authors.lastname: Cooksley
authors.forename: T
authors.initials: T
authors.lastname: Piratvisuth
authors.forename: S-D
authors.initials: SD
authors.lastname: Lee
authors.forename: V
authors.initials: V
authors.lastname: Mahachai
authors.forename: Y-C
authors.initials: YC
authors.lastname: Chao
authors.forename: T
authors.initials: T
authors.lastname: Tanwandee
authors.forename: A
authors.initials: A
authors.lastname: Chutaputti
authors.forename: W Yu
authors.initials: WY
authors.lastname: Chang
authors.forename: F E
authors.initials: FE
authors.lastname: Zahm
authors.forename: N
authors.initials: N
authors.lastname: Pluck
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006513:Hepatitis B e Antigens / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D011994:Recombinant Proteins; D012016:Reference Values; D018570:Risk Assessment; D012698:Serologic Tests; D016896:Treatment Outcome
chemical_list: D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a