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Tytuł:
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Entecavir Plus Pegylated Interferon and Sequential Hepatitis B Virus Vaccination Increases Hepatitis B Surface Antigen Seroclearance: A Randomized Controlled Proof-of-Concept Study.
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Autorzy:
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Lee JH; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Lee YB; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Cho EJ; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Yu SJ; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Yoon JH; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Kim YJ; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
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Źródło:
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Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2021 Nov 02; Vol. 73 (9), pp. e3308-e3316.
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Typ publikacji:
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Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: Jan. 2011- : Oxford : Oxford University Press
Original Publication: Chicago, IL : The University of Chicago Press, c1992-
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MeSH Terms:
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Hepatitis B Surface Antigens*
Hepatitis B, Chronic*/drug therapy
Hepatitis B, Chronic*/prevention & control
Antiviral Agents/therapeutic use ; DNA, Viral ; Guanine/analogs & derivatives ; Hepatitis B e Antigens ; Hepatitis B virus/genetics ; Humans ; Polyethylene Glycols/therapeutic use ; Recombinant Proteins/therapeutic use ; Vaccination
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Grant Information:
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Korea Health Technology R&D Project; Korea Health Industry Development Institute; HI16C1074 Ministry of Health and Welfare, Republic of Korea; 0620133790 Bristol-Myers Squibb; 0620140140 Roche; LG Life Science
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Contributed Indexing:
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Keywords: functional cure; hepatitis B virus; nucleoside analogue; therapeutic vaccination
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Molecular Sequence:
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ClinicalTrials.gov NCT02097004
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Substance Nomenclature:
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0 (Antiviral Agents)
0 (DNA, Viral)
0 (Hepatitis B Surface Antigens)
0 (Hepatitis B e Antigens)
0 (Recombinant Proteins)
3WJQ0SDW1A (Polyethylene Glycols)
5968Y6H45M (entecavir)
5Z93L87A1R (Guanine)
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Entry Date(s):
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Date Created: 20200620 Date Completed: 20211110 Latest Revision: 20211110
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Update Code:
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20240105
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DOI:
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10.1093/cid/ciaa807
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PMID:
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32556157
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Background: Hepatitis B surface antigen (HBsAg) seroclearance is considered a functional cure for patients with chronic hepatitis B, but is rarely achievable with oral nucleos(t)ide analogues alone. We conducted a randomized controlled proof-of-concept trial to evaluate the impact of adding pegylated interferon (peg-IFN) alfa-2a plus sequential or concomitant hepatitis B virus (HBV) vaccination.
Methods: A total of 111 patients who achieved serum HBV DNA <20 IU/mL and quantitative HBsAg <3000 IU/mL with entecavir were randomly assigned (1:1:1) to the E + sVIP group (entecavir + peg-IFN alfa-2a [180 µg every week over 48 weeks] plus sequential HBV vaccination [20 µg of HBsAg on weeks 52, 56, 60, and 76]), the E + cVIP group (entecavir + peg-IFN alfa-2a + concomitant HBV vaccination [weeks 4, 8, 12, and 28]), or the control group (entecavir only). The primary endpoint was HBsAg seroclearance at week 100, and secondary endpoints included safety.
Results: No differences in baseline quantitative HBsAg were observed among the groups. The E + sVIP group in the intention-to-treat analysis showed a significantly higher chance of HBsAg seroclearance during week 100 than the control group (16.2% vs 0%; P = .025), but the E + cVIP group (5.4%) failed to reach a significant difference (P = .54). Adverse events were significantly more frequent in the E + sVIP (81.1%) and E + cVIP group (70.3%) than the control group (2.7%) (both P < .0001). However, the frequency of serious adverse events did not differ significantly among the 3 groups (2.7%, 5.4%, and 2.7%, respectively; P = 1.00).
Conclusions: Entecavir plus an additional peg-IFN alfa-2a treatment followed by sequential HBV vaccination under an intensified schedule significantly increases the chance of HBsAg seroclearance compared to entecavir alone.
Clinical Trials Registration: NCT02097004.
(© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
