Back to Search
Start Over
Peginterferon lambda for the treatment of HBeAg-positive chronic hepatitis B: A randomized phase 2b study (LIRA-B).
- Source :
-
Journal of hepatology [J Hepatol] 2016 May; Vol. 64 (5), pp. 1011-1019. Date of Electronic Publication: 2015 Dec 29. - Publication Year :
- 2016
-
Abstract
- Background & Aims: 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.<br />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%.<br />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.<br />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.<br /> (Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Adult
Dose-Response Relationship, Drug
Double-Blind Method
Female
Follow-Up Studies
Hepatitis B, Chronic immunology
Hepatitis B, Chronic virology
Humans
Male
Time Factors
Treatment Outcome
Hepatitis B e Antigens immunology
Hepatitis B virus immunology
Hepatitis B, Chronic drug therapy
Interleukins administration & dosage
Polyethylene Glycols administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1600-0641
- Volume :
- 64
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of hepatology
- Publication Type :
- Academic Journal
- Accession number :
- 26739688
- Full Text :
- https://doi.org/10.1016/j.jhep.2015.12.018