title: A randomized, open-label clinical study of combined pegylated interferon Alfa-2a (40KD) and entecavir treatment for hepatitis B "e" antigen-positive chronic hepatitis B.
abstract: BACKGROUND
  Treatment with pegylated interferon (peg-IFN) alfa-2a (40KD) results in hepatitis B "e" antigen (HBeAg) seroconversion 6 months after treatment in up to 36% of HBeAg-positive chronic hepatitis B patients. This study explored the efficacy of a novel combination of peg-IFN alfa-2a and entecavir (ETV), a potent nucleoside analogue.
  
  
  METHODS
  In total, 218 treatment-naive Chinese HBeAg-positive patients were randomized to peg-IFN alfa-2a (180 µg/week) for 48 weeks, either as monotherapy (n = 72), or with 24 weeks of ETV (0.5 mg/daily) added at week 13 (ETV add-on, n = 73), or pretreatment with a 24-week course of ETV, starting peg-IFN alfa-2a at week 21 (ETV pretreatment, n = 73). The primary endpoint was reduction in quantitative HBeAg from baseline to 24 weeks posttreatment.
  
  
  RESULTS
  Significant reductions in HBeAg from baseline were achieved in all treatment groups 24 weeks posttreatment; reductions were comparable across treatment arms (shown as log10 Paul Ehrlich international units [PEIU]/mL): monotherapy: -1.4 (SD, 1.8); ETV add-on: -1.6 (SD, 1.8); ETV pretreatment: -1.3 (SD, 1.7). Rates of HBeAg seroconversion were similar across treatment groups posttreatment (monotherapy: 22 [31%]; ETV add-on: 18 [25%]; ETV pretreatment: 19 [26%]). Significantly greater reductions of hepatitis B virus DNA were achieved with ETV add-on while on treatment, but were not sustained posttreatment. Safety profiles were comparable between treatment groups; adverse events were experienced by 62 (86%) monotherapy, 65 (89%) ETV add-on, and 58 (81%) ETV pretreatment patients.
  
  
  CONCLUSIONS
  Neither ETV add-on nor ETV pretreatment demonstrated superiority compared with 48 weeks of peg-IFN alfa-2a monotherapy. The optimal treatment strategy using nucleos(t)ide analogues and peg-IFN alfa-2a remains to be determined. Clinical Trials Registration. NCT00614471.
authors.affiliation: Shanghai Ruijin Hospital, Jiao Tong University School of Medicine.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Shanghai Ruijin Hospital, Jiao Tong University School of Medicine.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shanxi Province.
authors.forename: Xuefan
authors.initials: X
authors.lastname: Bai
authors.affiliation: The First Affiliated Hospital of Zhengzhou University, Henan.
authors.forename: Shuhuan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Shanghai Shuguang Hospital affiliated with Shanghai University of Traditional Chinese Medicine.
authors.forename: Jian-Jie
authors.initials: JJ
authors.lastname: Chen
authors.affiliation: The First Hospital, Zhejiang University, Hangzhou.
authors.forename: Jifang
authors.initials: J
authors.lastname: Sheng
authors.affiliation: Beijing Ditan Hospital.
authors.forename: Yao
authors.initials: Y
authors.lastname: Xie
authors.affiliation: People's Liberation Army 85 Hospital, Shanghai.
authors.forename: Chengwei
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong.
authors.forename: Henry Lik-Yuen
authors.initials: HL
authors.lastname: Chan
authors.affiliation: Roche Pharmaceuticals Ltd, Shanghai, China.
authors.forename: Mianzhi
authors.initials: M
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C413685:entecavir; D006147:Guanine; C100416:peginterferon alfa-2a
keywords: clinical pharmacology; hepatitis B; liver; viral hepatitis