Add-on peginterferon alfa-2a to nucleos(t)ide analogue therapy for Caucasian patients with hepatitis B ‘e’ antigen-negative chronic hepatitis B genotype D

The HERMES Study Group, Pietro Lampertico, Maurizia R. Brunetto, Antonio Craxì, Giovanni B. Gaeta, Mario Rizzetto, Antonella Rozzi, Massimo Colombo

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Nucleos(t)ide analogues (NAs) and peginterferon have complementary effects in chronic hepatitis B, but it is unclear whether combination therapy improves responses in genotype D-infected patients. We conducted an open-label study of peginterferon alfa-2a 180 μg/wk added to ongoing NA therapy in hepatitis B e antigen (HBeAg)-negative, genotype D-infected patients with hepatitis B virus DNA <20 IU/mL. The primary endpoint was proportion of patients with ≥50% decline in serum HBsAg by the end of the 48-week add-on phase. Seventy patients received treatment, 11 were withdrawn at week 24 for no decrease in HBsAg, and 14 withdrew for other reasons. Response rate (per-protocol population) was 67.4% (29/43) at week 48 (95% confidence interval [CI]: 51, 81) and 50.9% (28/55) at week 96 (95% CI: 38, 66). Median serum HBsAg decreased throughout peginterferon alfa-2a treatment and was significantly lower than baseline at weeks 48, 72 and 96 (P < 0.001). Decreases in HBsAg of ≥0.5-log10 and ≥1-log10 were documented in 19 (44.2%) and 6 (14.0%) patients at week 48 and 6 (10.9%) and 17 (30.9%) patients at week 96. The proportion of patients with HBsAg <1000, <500, <100 and <10 IU/mL at ≥1 timepoint during treatment was 78.6% (n = 44), 57.1% (n = 32), 21.4% (n = 12) and 7.1% (n = 4). Interferon gamma-induced protein 10 increased from baseline up to week 48, with week 12 levels significantly associated with response at week 48. Addition of peginterferon alfa-2a to ongoing NA therapy significantly decreased HBsAg levels in HBeAg-negative patients with genotype D infection (ClinicalTrials.gov NCT01706575).

Original languageEnglish
Pages (from-to)118-125
JournalJournal of Viral Hepatitis
Volume26
Issue number1
DOIs
Publication statusPublished - 2019

Fingerprint

Hepatitis B e Antigens
Chronic Hepatitis B
Hepatitis B Surface Antigens
Genotype
Therapeutics
Confidence Intervals
peginterferon alfa-2a
Serum
Hepatitis B virus
Interferon-gamma
DNA
Infection

Keywords

  • chronic hepatitis B
  • HBeAg-negative
  • nucleos(t)ide analogues
  • peginterferon
  • treatment

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases
  • Virology

Cite this

Add-on peginterferon alfa-2a to nucleos(t)ide analogue therapy for Caucasian patients with hepatitis B ‘e’ antigen-negative chronic hepatitis B genotype D. / The HERMES Study Group ; Lampertico, Pietro; Brunetto, Maurizia R.; Craxì, Antonio; Gaeta, Giovanni B.; Rizzetto, Mario; Rozzi, Antonella; Colombo, Massimo.

In: Journal of Viral Hepatitis, Vol. 26, No. 1, 2019, p. 118-125.

Research output: Contribution to journalArticle

The HERMES Study Group ; Lampertico, Pietro ; Brunetto, Maurizia R. ; Craxì, Antonio ; Gaeta, Giovanni B. ; Rizzetto, Mario ; Rozzi, Antonella ; Colombo, Massimo. / Add-on peginterferon alfa-2a to nucleos(t)ide analogue therapy for Caucasian patients with hepatitis B ‘e’ antigen-negative chronic hepatitis B genotype D. In: Journal of Viral Hepatitis. 2019 ; Vol. 26, No. 1. pp. 118-125.
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T1 - Add-on peginterferon alfa-2a to nucleos(t)ide analogue therapy for Caucasian patients with hepatitis B ‘e’ antigen-negative chronic hepatitis B genotype D

AU - The HERMES Study Group

AU - Lampertico, Pietro

AU - Brunetto, Maurizia R.

AU - Craxì, Antonio

AU - Gaeta, Giovanni B.

AU - Rizzetto, Mario

AU - Rozzi, Antonella

AU - Colombo, Massimo

AU - Antonio, D.

AU - Andreone, P.

AU - Antonio, D.

AU - Brancaccio, G.

AU - Bronte, F.

AU - Bruzzone, L.

AU - Caccamo, G.

AU - Caccianotti, B.

AU - Calvaruso, V.

AU - Chessa, L.

AU - Ciarallo, M.

AU - Coco, B.

AU - Colombatto, P.

AU - Cursaro, C.

AU - D'Aluisio, D.

AU - Demelia, L.

AU - Di Marco, V.

AU - Dissegna, D.

AU - Invernizzi, F.

AU - Lenisa, I.

AU - Lembo, T.

AU - Levrero, M.

AU - Marchese, V.

AU - Mangia, G.

AU - Picciotto, A.

AU - Pierconti, S.

AU - Antonio, D.

AU - Raimondo, G.

AU - Rastelli, C.

AU - Rizzo, V.

AU - Santantonio, T.

AU - Scuteri, A.

AU - Sorbello, O.

AU - Squadrito, G.

AU - Subic, M.

AU - Toniutto, P.

AU - Vukotic, R.

PY - 2019

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N2 - Nucleos(t)ide analogues (NAs) and peginterferon have complementary effects in chronic hepatitis B, but it is unclear whether combination therapy improves responses in genotype D-infected patients. We conducted an open-label study of peginterferon alfa-2a 180 μg/wk added to ongoing NA therapy in hepatitis B e antigen (HBeAg)-negative, genotype D-infected patients with hepatitis B virus DNA <20 IU/mL. The primary endpoint was proportion of patients with ≥50% decline in serum HBsAg by the end of the 48-week add-on phase. Seventy patients received treatment, 11 were withdrawn at week 24 for no decrease in HBsAg, and 14 withdrew for other reasons. Response rate (per-protocol population) was 67.4% (29/43) at week 48 (95% confidence interval [CI]: 51, 81) and 50.9% (28/55) at week 96 (95% CI: 38, 66). Median serum HBsAg decreased throughout peginterferon alfa-2a treatment and was significantly lower than baseline at weeks 48, 72 and 96 (P < 0.001). Decreases in HBsAg of ≥0.5-log10 and ≥1-log10 were documented in 19 (44.2%) and 6 (14.0%) patients at week 48 and 6 (10.9%) and 17 (30.9%) patients at week 96. The proportion of patients with HBsAg <1000, <500, <100 and <10 IU/mL at ≥1 timepoint during treatment was 78.6% (n = 44), 57.1% (n = 32), 21.4% (n = 12) and 7.1% (n = 4). Interferon gamma-induced protein 10 increased from baseline up to week 48, with week 12 levels significantly associated with response at week 48. Addition of peginterferon alfa-2a to ongoing NA therapy significantly decreased HBsAg levels in HBeAg-negative patients with genotype D infection (ClinicalTrials.gov NCT01706575).

AB - Nucleos(t)ide analogues (NAs) and peginterferon have complementary effects in chronic hepatitis B, but it is unclear whether combination therapy improves responses in genotype D-infected patients. We conducted an open-label study of peginterferon alfa-2a 180 μg/wk added to ongoing NA therapy in hepatitis B e antigen (HBeAg)-negative, genotype D-infected patients with hepatitis B virus DNA <20 IU/mL. The primary endpoint was proportion of patients with ≥50% decline in serum HBsAg by the end of the 48-week add-on phase. Seventy patients received treatment, 11 were withdrawn at week 24 for no decrease in HBsAg, and 14 withdrew for other reasons. Response rate (per-protocol population) was 67.4% (29/43) at week 48 (95% confidence interval [CI]: 51, 81) and 50.9% (28/55) at week 96 (95% CI: 38, 66). Median serum HBsAg decreased throughout peginterferon alfa-2a treatment and was significantly lower than baseline at weeks 48, 72 and 96 (P < 0.001). Decreases in HBsAg of ≥0.5-log10 and ≥1-log10 were documented in 19 (44.2%) and 6 (14.0%) patients at week 48 and 6 (10.9%) and 17 (30.9%) patients at week 96. The proportion of patients with HBsAg <1000, <500, <100 and <10 IU/mL at ≥1 timepoint during treatment was 78.6% (n = 44), 57.1% (n = 32), 21.4% (n = 12) and 7.1% (n = 4). Interferon gamma-induced protein 10 increased from baseline up to week 48, with week 12 levels significantly associated with response at week 48. Addition of peginterferon alfa-2a to ongoing NA therapy significantly decreased HBsAg levels in HBeAg-negative patients with genotype D infection (ClinicalTrials.gov NCT01706575).

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