Peginterferon lambda for the treatment of HBeAg-positive chronic hepatitis B

A randomized phase 2b study (LIRA-B)

LIRA-B Study Team

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1011-1019
Number of pages9
JournalJournal of Hepatology
Volume64
Issue number5
DOIs
Publication statusPublished - 2016 May 1

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Hepatitis B e Antigens
Chronic Hepatitis B
Hepatitis B virus
DNA
Interferons
Therapeutics
Confidence Intervals
Virus Diseases
Bilirubin
Interferon-alpha
Hepacivirus
Antiviral Agents
Seroconversion
Liver

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

@article{2ee0adf35aff4c299e81fbb7a4c5c327,
title = "Peginterferon lambda for the treatment of HBeAg-positive chronic hepatitis B: A randomized phase 2b study (LIRA-B)",
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.",
author = "{LIRA-B Study Team} and Chan, {Henry L.Y.} and SangHoon Ahn and Chang, {Ting Tsung} and Peng, {Cheng Yuan} and David Wong and Coffin, {Carla S.} and Lim, {Seng Gee} and Chen, {Pei Jer} and Janssen, {Harry L.A.} and Patrick Marcellin and Lawrence Serfaty and Stefan Zeuzem and David Cohen and Linda Critelli and Dong Xu and Megan Wind-Rotolo and Elizabeth Cooney",
year = "2016",
month = "5",
day = "1",
doi = "10.1016/j.jhep.2015.12.018",
language = "English",
volume = "64",
pages = "1011--1019",
journal = "Journal of Hepatology",
issn = "0168-8278",
publisher = "Elsevier",
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}

Peginterferon lambda for the treatment of HBeAg-positive chronic hepatitis B : A randomized phase 2b study (LIRA-B). / LIRA-B Study Team.

In: Journal of Hepatology, Vol. 64, No. 5, 01.05.2016, p. 1011-1019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Peginterferon lambda for the treatment of HBeAg-positive chronic hepatitis B

T2 - A randomized phase 2b study (LIRA-B)

AU - LIRA-B Study Team

AU - Chan, Henry L.Y.

AU - Ahn, SangHoon

AU - Chang, Ting Tsung

AU - Peng, Cheng Yuan

AU - Wong, David

AU - Coffin, Carla S.

AU - Lim, Seng Gee

AU - Chen, Pei Jer

AU - Janssen, Harry L.A.

AU - Marcellin, Patrick

AU - Serfaty, Lawrence

AU - Zeuzem, Stefan

AU - Cohen, David

AU - Critelli, Linda

AU - Xu, Dong

AU - Wind-Rotolo, Megan

AU - Cooney, Elizabeth

PY - 2016/5/1

Y1 - 2016/5/1

N2 - 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.

AB - 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.

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U2 - 10.1016/j.jhep.2015.12.018

DO - 10.1016/j.jhep.2015.12.018

M3 - Article

VL - 64

SP - 1011

EP - 1019

JO - Journal of Hepatology

JF - Journal of Hepatology

SN - 0168-8278

IS - 5

ER -