title: Shorter durations and lower doses of peginterferon alfa-2a are associated with inferior hepatitis B e antigen seroconversion rates in hepatitis B virus genotypes B or C.
abstract: As there is currently a lack of consensus on the most appropriate dose and duration of peginterferon alfa-2a (PEG-IFNα-2a) therapy in hepatitis B e antigen (HBeAg)-positive patients, the efficacy and safety of either 24 or 48 weeks' duration and 90 μg/week or 180 μg/week doses were compared. HBeAg-positive patients (n = 544; 34% genotype B, 51% genotype C) were randomized to receive PEG-IFNα-2a (2 × 2 factorial design) for 24 or 48 weeks and at 90 μg/week or 180 μg/week and included in the per-protocol population. The primary efficacy endpoint of the noninferiority study was HBeAg seroconversion 6 months posttreatment. The prespecified odds ratio (OR) noninferiority margin was 1.88 with a one-sided significance level of 0.025. The highest rates of HBeAg seroconversion 6 months posttreatment were in the 180/48 arm (36.2% versus 14.1%-25.8% in the other arms). When the dose and duration arms were pooled, the OR for noninferiority of 24 weeks versus 48 weeks was 2.17 (95% confidence interval [CI] 1.43, 3.31; P = 0.749) and for 90 μg versus 180 μg was 1.79 (95% CI 1.18, 2.72; P = 0.410). As the upper limit of the 95% CI of the ORs were >1.88, 24 weeks were inferior to 48 weeks and 90 μg/week was inferior to 180 μg/week. The highest rates of response in the 180/48 arm were achieved by patients with HBsAg <1,500 IU/mL at Week 12 (58%) or Week 24 (57%), whereas patients with HBsAg >20,000 IU/mL did not respond. Adverse events were typical of those associated with PEG-IFNα-2a.
  
  
  CONCLUSIONS
  Compared with lower doses and shorter durations, the licensed PEG-IFNα-2a treatment regimen (180 μg/48 weeks) was the most efficacious and beneficial for HBeAg-positive patients predominantly infected with hepatitis B virus genotypes B or C.
authors: Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan. liveryfl@gmail.com
authors: Y-F
authors: YF
authors: Liaw
authors: J-D
authors: JD
authors: Jia
authors: H L Y
authors: HL
authors: Chan
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authors: Han
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authors: Tanwandee
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authors: Gane
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authors: Piratvisuth
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authors: Chen
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authors: Xie
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authors: JJ
authors: Sung
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authors: Wat
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authors: Bernaards
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authors: Cui
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authors: Marcellin
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005838:Genotype; D006510:Hepatitis B Antibodies / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a