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

LIRA-B Study Team

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36 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

Bibliographical note

Funding Information:
This study was sponsored by Bristol-Myers Squibb . The study was designed and conducted by the sponsor in collaboration with the principal investigators. The sponsor collected the data, monitored the study conduct, and performed the statistical analyses.

Funding Information:
HLC: advisor and speaker for Bristol-Myers Squibb, Gilead, Roche, Novartis and MSD, a speaker for GlaxoSmithKline, Echosens and AbbVie, and has received an unrestricted grant for hepatitis B research from Roche; SHA: advisor and speaker for Bristol-Myers Squibb, Gilead, Roche, Novartis, MSD, Janssen, and AbbVie; and has received an unrestricted grant for hepatitis B research from Bristol-Myers Squibb, Gilead, and Roche; TTC: nothing to disclose; CYP; nothing to disclose; DW: nothing to disclose; CC: supported by the Canadian institutes of Health Research and has received speaker and advisory board fees and/or research support from Bristol-Myers Squibb, GlaxoSmithKline, Gilead, Janssen Pharmaceuticals, Boehringer Ingelheim, and Merck; SGL: advisory board fees from Gilead, Novartis, Merck Sharpe and Dohme, Bristol-Myers Squibb, Pfizer, Boehringer Ingelheim, AbbVie, Vertex, Tobira, speakers’ bureau for Gilead, GlaxoSmithKline, Bristol-Myers Squibb, Novartis, Roche, and educational/research funding from Bristol-Myers Squibb, Novartis, Merck Sharpe and Dohme, and Gilead; PJC: personal fees and other from Bristol-Myers Squibb, grants from Roche and Janssen, and personal fees from Gilead; HLAJ: nothing to disclose; PM: grant, investigator, speaker, and expert for Roche, Gilead, Bristol-Myers Squibb, Novartis, Merck Sharpe and Dohme, and Janssen, investigator and expert for Vertex, and Abbott, grant and investigator for Alios BioPharma, and investigator for Pfizer, and Boehringer Ingelheim; LS: personal fees from Bristol-Myers Squibb, Janssen, Merck Sharpe and Dohme, Gilead, AbbVie, and Roche; SZ: consultancy for AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Merck, speakers’ bureau for AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Merck/Merck Sharpe and Dohme; DC, LC, DX, MWR, and EC are employees of Bristol-Myers Squibb.

Funding Information:
This study was funded by Bristol-Myers Squibb. Editorial assistance was provided by Stephen Griffiths, PhD of Articulate Science Ltd. and was funded by Bristol-Myers Squibb.

Publisher Copyright:
© 2016 European Association for the Study of the Liver.

All Science Journal Classification (ASJC) codes

  • Hepatology

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