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 Seventy patients received treatment, 11 were withdrawn at week 24 for no decrease in HBsAg, and 14 withdrew for other reasons.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-log 10 and ≥1-log 10 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).

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 / Lampertico, P.; Brunetto, M. R.; Craxi, A.; Gaeta, G. B.; Rizzetto, M.; Rozzi, A.; Colombo, M.; Antonio, D.; Andreone, P.; Antonio, D.; Brancaccio, G.; Bronte, F.; Bruzzone, L.; Caccamo, G.; Caccianotti, B.; Calvaruso, V.; Chessa, L.; Ciarallo, M.; Coco, B.; Colombatto, P.; Cursaro, C.; D'Aluisio, D.; Demelia, L.; Di Marco, V.; Dissegna, D.; Invernizzi, F.; Lenisa, I.; Lembo, T.; Levrero, M.; Marchese, V.; Mangia, G.; Picciotto, A.; Pierconti, S.; Antonio, D.; Raimondo, G.; Rastelli, C.; Rizzo, V.; Santantonio, T.; Scuteri, A.; Sorbello, O.; Squadrito, G.; Subic, M.; Toniutto, P.; Vukotic, R.. - In: JOURNAL OF VIRAL HEPATITIS. - ISSN 1352-0504. - 26:1(2019), pp. 118-125. [10.1111/jvh.12999]

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

Chessa L.;D'Aluisio D.;Levrero M.;Pierconti S.;Subic M.;
2019

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-log 10 and ≥1-log 10 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).
2019
chronic hepatitis b; hbeag-negative; nucleos(t)ide analogues; peginterferon; treatment; adult; antiviral agents; drug administration schedule; drug therapy, combination; female; genotype; hepatitis b e antigens; hepatitis b virus; hepatitis b, chronic; humans; interferon-alpha; male; middle aged; nucleosides; polyethylene glycols; recombinant proteins; treatment outcome
01 Pubblicazione su rivista::01a Articolo in rivista
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 / Lampertico, P.; Brunetto, M. R.; Craxi, A.; Gaeta, G. B.; Rizzetto, M.; Rozzi, A.; Colombo, M.; Antonio, D.; Andreone, P.; Antonio, D.; Brancaccio, G.; Bronte, F.; Bruzzone, L.; Caccamo, G.; Caccianotti, B.; Calvaruso, V.; Chessa, L.; Ciarallo, M.; Coco, B.; Colombatto, P.; Cursaro, C.; D'Aluisio, D.; Demelia, L.; Di Marco, V.; Dissegna, D.; Invernizzi, F.; Lenisa, I.; Lembo, T.; Levrero, M.; Marchese, V.; Mangia, G.; Picciotto, A.; Pierconti, S.; Antonio, D.; Raimondo, G.; Rastelli, C.; Rizzo, V.; Santantonio, T.; Scuteri, A.; Sorbello, O.; Squadrito, G.; Subic, M.; Toniutto, P.; Vukotic, R.. - In: JOURNAL OF VIRAL HEPATITIS. - ISSN 1352-0504. - 26:1(2019), pp. 118-125. [10.1111/jvh.12999]
File allegati a questo prodotto
File Dimensione Formato  
Lampertico_Add-On-Peginterferon_2018.pdf

solo gestori archivio

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 384.54 kB
Formato Adobe PDF
384.54 kB Adobe PDF   Contatta l'autore

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1479955
Citazioni
  • ???jsp.display-item.citation.pmc??? 9
  • Scopus 18
  • ???jsp.display-item.citation.isi??? 17
social impact