title: Peginterferon lambda for the treatment of HBeAg-positive chronic hepatitis B: A randomized phase 2b study (LIRA-B).
abstract: OBJECTIVE
  Peginterferon lambda-1a (lambda) is a Type-III interferon, which, like alfa interferons, has antiviral activity in vitro against hepatitis B virus (HBV) and hepatitis C virus (HCV); however, lambda has a more limited extra-hepatic receptor distribution. This phase 2b study (LIRA-B) evaluated lambda in patients with chronic HBV infection.
  
  
  METHODS
  Adult HBeAg+ interferon-naive patients were randomized (1:1) to weekly lambda (180 μg) or peginterferon alfa-2a (alfa) for 48 weeks. The primary efficacy endpoint was HBeAg seroconversion at week 24 post-treatment; lambda non-inferiority was demonstrated if the 80% confidence interval (80% CI) lower bound was >-15%.
  
  
  RESULTS
  Baseline characteristics were balanced across groups (lambda N=80; alfa N=83). Early on-treatment declines in HBV-DNA and qHBsAg through week 24 were greater with lambda. HBeAg seroconversion rates were comparable for lambda and alfa at week 48 (17.5% vs. 16.9%, respectively); however lambda non-inferiority was not met at week 24 post-treatment (13.8% vs. 30.1%, respectively; lambda vs. alfa 80% CI lower bound -24%). Results for other key secondary endpoints (virologic, serologic, biochemical) and post hoc combined endpoints (HBV-DNA <2000 IU/ml plus HBeAg seroconversion or ALT normalization) mostly favored alfa. Overall adverse events (AE), serious AE, and AE-discontinuation rates were comparable between arms but AE-spectra differed (more cytopenias, flu-like, and musculoskeletal symptoms observed with alfa, more ALT flares and bilirubin elevations seen with lambda). Most on-treatment flares occurred early (weeks 4-12), associated with HBV-DNA decline; all post-treatment flares were preceded by HBV-DNA rise.
  
  
  CONCLUSIONS
  On-treatment, lambda showed greater early effects on HBV-DNA and qHBsAg, and comparable serologic/virologic responses at end-of-treatment. However, post-treatment, alfa-associated HBeAg seroconversion rates were higher, and key secondary results mostly favored alfa. ClinicalTrials.gov number: NCT01204762.
authors.affiliation: The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Henry L Y
authors.initials: HLY
authors.lastname: Chan
authors.affiliation: Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Ahn
authors.affiliation: National Cheng Kung University Hospital, Tainan, Taiwan.
authors.forename: Ting-Tsung
authors.initials: TT
authors.lastname: Chang
authors.affiliation: China Medical University Hospital, Taichung, Taiwan.
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Peng
authors.affiliation: Toronto Western Hospital University Health Network, Toronto, ON, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Wong
authors.affiliation: Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Carla S
authors.initials: CS
authors.lastname: Coffin
authors.affiliation: National University Hospital, Singapore.
authors.forename: Seng Gee
authors.initials: SG
authors.lastname: Lim
authors.affiliation: National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Pei-Jer
authors.initials: PJ
authors.lastname: Chen
authors.affiliation: Erasmus Medical Center, Rotterdam, Netherlands; University Health Network, Toronto, Canada.
authors.forename: Harry L A
authors.initials: HLA
authors.lastname: Janssen
authors.affiliation: Hôpital Beaujon and INSERM CRI Université Paris Diderot, Clichy, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.affiliation: Hôpital Saint Antoine, Paris, France.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Serfaty
authors.affiliation: Johann Wolfgang Goethe University, Frankfurt, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.affiliation: Bristol-Myers Squibb Research and Development, Wallingford, CT, USA.
authors.forename: David
authors.initials: D
authors.lastname: Cohen
authors.affiliation: Bristol-Myers Squibb Research and Development, Wallingford, CT, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Critelli
authors.affiliation: Bristol-Myers Squibb Research and Development, Wallingford, CT, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Xu
authors.affiliation: Bristol-Myers Squibb Research and Development, Lawrenceville, NJ, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Wind-Rotolo
authors.affiliation: Bristol-Myers Squibb Research and Development, Wallingford, CT, USA. Electronic address: elizabeth.cooney@bms.com.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Cooney
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006513:Hepatitis B e Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D007378:Interleukins / Q000008:administration & dosage*; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D000095022:Interferon Lambda
chemical_list: D006513:Hepatitis B e Antigens; D007378:Interleukins; D011092:Polyethylene Glycols; C000600496:peginterferon lambda-1a; D000095022:Interferon Lambda
keywords: Human; Immunomodulatory therapy; Viral hepatitis