Low hepatitis B surface antigen and HBV DNA levels predict response to the addition of pegylated interferon to entecavir in hepatitis B e antigen positive chronic hepatitis B.
Adult
Antiviral Agents
/ administration & dosage
DNA, Viral
Drug Therapy, Combination
Female
Guanine
/ administration & dosage
Hepatitis B Surface Antigens
/ blood
Hepatitis B e Antigens
/ blood
Hepatitis B, Chronic
/ drug therapy
Humans
Interferon-alpha
/ administration & dosage
Male
Polyethylene Glycols
/ chemistry
Young Adult
Journal
Alimentary pharmacology & therapeutics
ISSN: 1365-2036
Titre abrégé: Aliment Pharmacol Ther
Pays: England
ID NLM: 8707234
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
04
04
2018
revised:
23
04
2018
accepted:
20
11
2018
entrez:
29
1
2019
pubmed:
29
1
2019
medline:
7
1
2020
Statut:
ppublish
Résumé
Various treatment combinations of peginterferon (PEG-IFN) and nucleos(t)ide analogues have been evaluated for chronic hepatitis B (CHB), but the optimal regimen remains unclear. To study whether PEG-IFN add-on increases response compared to entecavir (ETV) monotherapy, and whether the duration of ETV pretreatment influences response. Response was evaluated in HBeAg positive patients previously treated in two randomized controlled trials. Patients received ETV pretreatment for at least 24 weeks and were then allocated to 24-48 weeks of ETV+PEG-IFN add-on, or continued ETV monotherapy. Response was defined as HBeAg loss combined with HBV DNA <200 IU/mL 48 weeks after discontinuing PEG-IFN. Of 234 patients, 118 were assigned PEG-IFN add-on and 116 continued ETV monotherapy. Response was observed in 38/118 (33%) patients treated with add-on therapy and in 23/116 (20%) with monotherapy (P = 0.03). The highest response to add-on therapy compared to monotherapy was observed in PEG-IFN naive patients with HBsAg levels below 4000 IU/mL and HBV DNA levels below 50 IU/mL at randomization (70% vs 34%; P = 0.01). Above the cut-off levels, response was low and not significantly different between treatment groups. Duration of ETV pretreatment was associated with HBsAg and HBV DNA levels (both P < 0.005), but not with response (P = 0.82). PEG-IFN add-on to ETV therapy was associated with higher response compared to ETV monotherapy in patients with HBeAg positive CHB. Response doubled in PEG-IFN naive patients with HBsAg below 4000 IU/mL and HBV DNA below 50 IU/mL, and therefore identifies them as the best candidates for PEG-IFN add-on (Identifiers: NCT00877760, NCT01532843).
Sections du résumé
BACKGROUND
Various treatment combinations of peginterferon (PEG-IFN) and nucleos(t)ide analogues have been evaluated for chronic hepatitis B (CHB), but the optimal regimen remains unclear.
AIMS
To study whether PEG-IFN add-on increases response compared to entecavir (ETV) monotherapy, and whether the duration of ETV pretreatment influences response.
METHODS
Response was evaluated in HBeAg positive patients previously treated in two randomized controlled trials. Patients received ETV pretreatment for at least 24 weeks and were then allocated to 24-48 weeks of ETV+PEG-IFN add-on, or continued ETV monotherapy. Response was defined as HBeAg loss combined with HBV DNA <200 IU/mL 48 weeks after discontinuing PEG-IFN.
RESULTS
Of 234 patients, 118 were assigned PEG-IFN add-on and 116 continued ETV monotherapy. Response was observed in 38/118 (33%) patients treated with add-on therapy and in 23/116 (20%) with monotherapy (P = 0.03). The highest response to add-on therapy compared to monotherapy was observed in PEG-IFN naive patients with HBsAg levels below 4000 IU/mL and HBV DNA levels below 50 IU/mL at randomization (70% vs 34%; P = 0.01). Above the cut-off levels, response was low and not significantly different between treatment groups. Duration of ETV pretreatment was associated with HBsAg and HBV DNA levels (both P < 0.005), but not with response (P = 0.82).
CONCLUSIONS
PEG-IFN add-on to ETV therapy was associated with higher response compared to ETV monotherapy in patients with HBeAg positive CHB. Response doubled in PEG-IFN naive patients with HBsAg below 4000 IU/mL and HBV DNA below 50 IU/mL, and therefore identifies them as the best candidates for PEG-IFN add-on (Identifiers: NCT00877760, NCT01532843).
Identifiants
pubmed: 30689258
doi: 10.1111/apt.15098
pmc: PMC6590282
doi:
Substances chimiques
Antiviral Agents
0
DNA, Viral
0
Hepatitis B Surface Antigens
0
Hepatitis B e Antigens
0
Interferon-alpha
0
Polyethylene Glycols
3WJQ0SDW1A
entecavir
5968Y6H45M
Guanine
5Z93L87A1R
Banques de données
ClinicalTrials.gov
['NCT00877760', 'NCT01532843']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
448-456Subventions
Organisme : Foundation for Liver Research, Rotterdam, The Netherlands
Pays : International
Commentaires et corrections
Type : CommentIn
Informations de copyright
©2019 The Authors. Alimentary Pharmacology & Therapeutics Published by John Wiley & Sons Ltd.
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