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

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• 作者：Henry L.Y. Chan<sup>1sup> ; Sang Hoon Ahn<sup>2sup> ; Ting-Tsung Chang<sup>3sup> ; Cheng-Yuan Peng<sup>4sup> ; David Wong<sup>5sup> ; Carla S. Coffin<sup>6sup> ; Seng Gee Lim<sup>7sup> ; Pei-Jer Chen<sup>8sup> ; Harry L.A. Janssen<sup>9sup><sup> ; sup><sup>10sup> ; Patrick Marcellin<sup>11sup> ; Lawrence Serfaty<sup>12sup> ; Stefan Zeuzem<sup>13sup> ; David Cohen<sup>14sup> ; Linda Critelli<sup>14sup> ; Dong Xu<sup>14sup> ; Megan Wind-Rotolo<sup>15sup> ; Elizabeth Cooney<sup>14sup><sup> ; sup><sup>elizabeth.cooney@bms.com" class="auth_mail" title="E-mail the corresponding authorsup> ; ; the LIRA-B Study Team<sup>&dagger ; sup>
• 关键词：80% CIs ; 80% confidence intervals ; AE ; adverse event ; alfa ; peginterferon alfa-2a ; CHB ; chronic hepatitis B ; CHC ; chronic hepatitis C ; HBeAb ; hepatitis B e antibody ; HBsAb ; hepatitis B surface antibody ; IFN ; interferon ; ISG ; IFN-stimulated gene ; HBeAg+ ; HBeAg-positive ; HBsAg+ ; HBsAg-positive ; Hgb ; hemoglobin ; lambda ; peginterferon lambda-1a ; LLOD ; lower limit of detection ; LLOQ ; lower limit of quantification ; mITT ; modified intent-to-treat ; NA ; nucleos(t)ide analogue ; NK ; natural killer ; pegIFN-
• 刊名：Journal of Hepatology
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：64
• 期：5
• 页码：1011-1019
• 全文大小：849 K

文摘

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.

sSec_2">Methods

sp0010">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 >&minus;15%.

sSec_3">Results

sp0015">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 &minus;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&ndash;12), associated with HBV-DNA decline; all post-treatment flares were preceded by HBV-DNA rise.

sSec_4">Conclusions

sp0020">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.

sp0025">ClinicalTrials.gov number: NCT01204762.