Peginterferon lambda for the treatment of HBeAg-positive chronic hepatitis B: A randomized phase 2b study (LIRA-B)
Journal
Journal of Hepatology
Journal Volume
64
Journal Issue
5
Pages
1011-1019
Date Issued
2016
Author(s)
Chan H.L.Y.
Ahn S.H.
Chang T.-T.
Peng C.-Y.
Wong D.
Coffin C.S.
Lim S.G.
Janssen H.L.A.
Marcellin P.
Serfaty L.
Zeuzem S.
Cohen D.
Critelli L.
Xu D.
Wind-Rotolo M.
Cooney E.
LIRA-B Study Team
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. 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. ? 2016 European Association for the Study of the Liver.
Subjects
Human.; Immunomodulatory therapy; Viral hepatitis
SDGs
Other Subjects
alanine aminotransferase; bilirubin; hepatitis B surface antigen; hepatitis B(e) antigen; peginterferon alpha2a; peginterferon lambda; virus DNA; hepatitis B(e) antigen; interleukin derivative; macrogol derivative; peginterferon lambda; adult; alanine aminotransferase blood level; alopecia; antiviral therapy; Article; bilirubin blood level; chronic hepatitis B; controlled study; cytopenia; dizziness; double blind procedure; drug dose reduction; drug efficacy; drug safety; drug withdrawal; fatigue; female; fever; flu like syndrome; headache; Hepatitis B virus; human; hyperbilirubinemia; hypertransaminasemia; leukopenia; major clinical study; male; mental disease; middle aged; monotherapy; multicenter study; musculoskeletal disease; myalgia; neurologic disease; neutropenia; phase 2 clinical trial; priority journal; pruritus; randomized controlled trial; seroconversion; thrombocytopenia; treatment response; young adult; clinical trial; dose response; follow up; Hepatitis B, Chronic; immunology; time factor; treatment outcome; virology; Adult; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Hepatitis B e Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Interleukins; Male; Polyethylene Glycols; Time Factors; Treatment Outcome
Publisher
Elsevier B.V.
Type
journal article