Responses are durable for up to 5 years after completion of peginterferon alfa-2a treatment in hepatitis B e antigen-positive patients

W. L. Chuang; J. Jia; H. L.Y. Chan; K. H. Han; T. Tanwandee; D. Tan; X. Chen; E. Gane; T. Piratvisuth; L. Chen; Q. Xie; J. J.Y. Sung; D. Messinger; C. Wat; G. Bakalos; Y. F. Liaw

doi:10.1111/apt.14595

Responses are durable for up to 5 years after completion of peginterferon alfa-2a treatment in hepatitis B e antigen-positive patients

W. L. Chuang, J. Jia, H. L.Y. Chan, K. H. Han, T. Tanwandee, D. Tan, X. Chen, E. Gane, T. Piratvisuth, L. Chen, Q. Xie, J. J.Y. Sung, D. Messinger, C. Wat, G. Bakalos, Y. F. Liaw

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

Background: In the large randomised NEPTUNE study, peginterferon alfa-2a 180 μg/wk for 48 weeks produced higher hepatitis B e antigen (HBeAg) seroconversion rates 24 weeks post-treatment (36%) than a lower dose (90 μg/wk) and/or shorter duration (24 weeks) (range 14%-26%). Aim: To determine seroconversion rates 5 years after completion of treatment in NEPTUNE. Methods: HBeAg-positive patients who completed 24 weeks’ follow-up in NEPTUNE (with peginterferon alfa-2a 90 μg/wk × 24 weeks [group 1]; 180 μg/wk × 24 weeks [2]; 90 μg/wk × 48 weeks [3] or 180 μg/wk × 48 weeks [4]) were followed up. Results: Three hundred and eighty three of the 544 patients in the original study were enrolled in the long-term follow-up study. Many patients (196 overall; more in groups 1-3 than 4) received nucleos(t)ide analogues or immunomodulators during follow-up, and more patients had missing data at year 5 in groups 2 and 4 (48 weeks, 50/112) than in groups 1 and 3 (24 weeks, 23/103), which confounds the planned per-protocol analysis. HBeAg seroconversion rates in groups 1, 2, 3 and 4 at year 5 were 47.5%, 50.7%, 52.2% and 67.1%, respectively, (odds ratio for group 4 versus 1-3: 2.02; 95% CI 1.21, 3.38), using multiple imputation methods for missing measurements. Conclusion: Seroconversion rates are durable for up to 5 years after completion of peginterferon alfa-2a therapy and, consistent with NEPTUNE, the results suggest that the licensed regimen (180 μg × 48 weeks) is more efficacious for HBeAg-positive patients than a lower dose and/or shorter treatment duration.

Original language	English
Pages (from-to)	1306-1316
Number of pages	11
Journal	Alimentary Pharmacology and Therapeutics
Volume	47
Issue number	9
DOIs	https://doi.org/10.1111/apt.14595
Publication status	Published - 2018 May

Bibliographical note

Funding Information:
Declaration of funding interests: This research was funded by F. Hoffmann-La Roche Ltd., Basel, Switzerland. Support for third-party writing assistance furnished by Blair Jarvis, Health Interactions, was provided by F. Hoffmann-La Roche Ltd., Basel, Switzerland.

Funding Information:
Declaration of personal interests: Consultancy, speakers’ bureau and stock ownership-Roche, BMS, Gilead, AbbVie. Consultancy-Janssen. Speakers’ bureau-MSD: Henry Lik-Yuen Chan. Advisory arrangements and speakers’ bureau-Gilead and AbbVie. Advisory arrangements-Janssen/Alios: Edward Gane. Research Grants-Roche, Gilead, Novartis, MSD, Covance, GSK, Bayer, BMS, Fibrogen. Speakers’ bureau-Roche, Gilead, Novartis, MSD, GSK, Bayer, BMS; Advisory arrangements-Roche, MSD: Teerha Piratvisuth. Employment-PROMETRIS GmbH, which has a contract with Roche to provide statistical support: Diethelm Messinger. Employment and stock ownership-Roche: Cynthia Wat. Employment-Roche: Georgios Bakalos. Wan-Long Chuang, Jidong Jia, Kwang-Hyub Han, Tawesak Tanwandee, Deming Tan, Xinyue Chen, Liang Chen, Qing Xie, Joseph Jao-Yiu Sung and Yun-Fan Liaw have no relationships to disclose. Declaration of funding interests: This research was funded by F. Hoffmann-La Roche Ltd., Basel, Switzerland. Support for third-party writing assistance furnished by Blair Jarvis, Health Interactions, was provided by F. Hoffmann-La Roche Ltd., Basel, Switzerland.

Publisher Copyright:
© 2018 John Wiley & Sons Ltd

All Science Journal Classification (ASJC) codes

Hepatology
Gastroenterology
Pharmacology (medical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1111/apt.14595

Cite this

Chuang, W. L., Jia, J., Chan, H. L. Y., Han, K. H., Tanwandee, T., Tan, D., Chen, X., Gane, E., Piratvisuth, T., Chen, L., Xie, Q., Sung, J. J. Y., Messinger, D., Wat, C., Bakalos, G., & Liaw, Y. F. (2018). Responses are durable for up to 5 years after completion of peginterferon alfa-2a treatment in hepatitis B e antigen-positive patients. Alimentary Pharmacology and Therapeutics, 47(9), 1306-1316. https://doi.org/10.1111/apt.14595

@article{b14aece2a73e41f0bb6bb8f3a3d8dd7a,

title = "Responses are durable for up to 5 years after completion of peginterferon alfa-2a treatment in hepatitis B e antigen-positive patients",

abstract = "Background: In the large randomised NEPTUNE study, peginterferon alfa-2a 180 μg/wk for 48 weeks produced higher hepatitis B e antigen (HBeAg) seroconversion rates 24 weeks post-treatment (36%) than a lower dose (90 μg/wk) and/or shorter duration (24 weeks) (range 14%-26%). Aim: To determine seroconversion rates 5 years after completion of treatment in NEPTUNE. Methods: HBeAg-positive patients who completed 24 weeks{\textquoteright} follow-up in NEPTUNE (with peginterferon alfa-2a 90 μg/wk × 24 weeks [group 1]; 180 μg/wk × 24 weeks [2]; 90 μg/wk × 48 weeks [3] or 180 μg/wk × 48 weeks [4]) were followed up. Results: Three hundred and eighty three of the 544 patients in the original study were enrolled in the long-term follow-up study. Many patients (196 overall; more in groups 1-3 than 4) received nucleos(t)ide analogues or immunomodulators during follow-up, and more patients had missing data at year 5 in groups 2 and 4 (48 weeks, 50/112) than in groups 1 and 3 (24 weeks, 23/103), which confounds the planned per-protocol analysis. HBeAg seroconversion rates in groups 1, 2, 3 and 4 at year 5 were 47.5%, 50.7%, 52.2% and 67.1%, respectively, (odds ratio for group 4 versus 1-3: 2.02; 95% CI 1.21, 3.38), using multiple imputation methods for missing measurements. Conclusion: Seroconversion rates are durable for up to 5 years after completion of peginterferon alfa-2a therapy and, consistent with NEPTUNE, the results suggest that the licensed regimen (180 μg × 48 weeks) is more efficacious for HBeAg-positive patients than a lower dose and/or shorter treatment duration.",

author = "Chuang, {W. L.} and J. Jia and Chan, {H. L.Y.} and Han, {K. H.} and T. Tanwandee and D. Tan and X. Chen and E. Gane and T. Piratvisuth and L. Chen and Q. Xie and Sung, {J. J.Y.} and D. Messinger and C. Wat and G. Bakalos and Liaw, {Y. F.}",

note = "Funding Information: Declaration of funding interests: This research was funded by F. Hoffmann-La Roche Ltd., Basel, Switzerland. Support for third-party writing assistance furnished by Blair Jarvis, Health Interactions, was provided by F. Hoffmann-La Roche Ltd., Basel, Switzerland. Funding Information: Declaration of personal interests: Consultancy, speakers{\textquoteright} bureau and stock ownership-Roche, BMS, Gilead, AbbVie. Consultancy-Janssen. Speakers{\textquoteright} bureau-MSD: Henry Lik-Yuen Chan. Advisory arrangements and speakers{\textquoteright} bureau-Gilead and AbbVie. Advisory arrangements-Janssen/Alios: Edward Gane. Research Grants-Roche, Gilead, Novartis, MSD, Covance, GSK, Bayer, BMS, Fibrogen. Speakers{\textquoteright} bureau-Roche, Gilead, Novartis, MSD, GSK, Bayer, BMS; Advisory arrangements-Roche, MSD: Teerha Piratvisuth. Employment-PROMETRIS GmbH, which has a contract with Roche to provide statistical support: Diethelm Messinger. Employment and stock ownership-Roche: Cynthia Wat. Employment-Roche: Georgios Bakalos. Wan-Long Chuang, Jidong Jia, Kwang-Hyub Han, Tawesak Tanwandee, Deming Tan, Xinyue Chen, Liang Chen, Qing Xie, Joseph Jao-Yiu Sung and Yun-Fan Liaw have no relationships to disclose. Declaration of funding interests: This research was funded by F. Hoffmann-La Roche Ltd., Basel, Switzerland. Support for third-party writing assistance furnished by Blair Jarvis, Health Interactions, was provided by F. Hoffmann-La Roche Ltd., Basel, Switzerland. Publisher Copyright: {\textcopyright} 2018 John Wiley & Sons Ltd",

year = "2018",

month = may,

doi = "10.1111/apt.14595",

language = "English",

volume = "47",

pages = "1306--1316",

journal = "Alimentary Pharmacology and Therapeutics",

issn = "0269-2813",

publisher = "Wiley-Blackwell",

number = "9",

}

Chuang, WL, Jia, J, Chan, HLY, Han, KH, Tanwandee, T, Tan, D, Chen, X, Gane, E, Piratvisuth, T, Chen, L, Xie, Q, Sung, JJY, Messinger, D, Wat, C, Bakalos, G & Liaw, YF 2018, 'Responses are durable for up to 5 years after completion of peginterferon alfa-2a treatment in hepatitis B e antigen-positive patients', Alimentary Pharmacology and Therapeutics, vol. 47, no. 9, pp. 1306-1316. https://doi.org/10.1111/apt.14595

TY - JOUR

T1 - Responses are durable for up to 5 years after completion of peginterferon alfa-2a treatment in hepatitis B e antigen-positive patients

AU - Chuang, W. L.

AU - Jia, J.

AU - Chan, H. L.Y.

AU - Han, K. H.

AU - Tanwandee, T.

AU - Tan, D.

AU - Chen, X.

AU - Gane, E.

AU - Piratvisuth, T.

AU - Chen, L.

AU - Xie, Q.

AU - Sung, J. J.Y.

AU - Messinger, D.

AU - Wat, C.

AU - Bakalos, G.

AU - Liaw, Y. F.

N1 - Funding Information: Declaration of funding interests: This research was funded by F. Hoffmann-La Roche Ltd., Basel, Switzerland. Support for third-party writing assistance furnished by Blair Jarvis, Health Interactions, was provided by F. Hoffmann-La Roche Ltd., Basel, Switzerland. Funding Information: Declaration of personal interests: Consultancy, speakers’ bureau and stock ownership-Roche, BMS, Gilead, AbbVie. Consultancy-Janssen. Speakers’ bureau-MSD: Henry Lik-Yuen Chan. Advisory arrangements and speakers’ bureau-Gilead and AbbVie. Advisory arrangements-Janssen/Alios: Edward Gane. Research Grants-Roche, Gilead, Novartis, MSD, Covance, GSK, Bayer, BMS, Fibrogen. Speakers’ bureau-Roche, Gilead, Novartis, MSD, GSK, Bayer, BMS; Advisory arrangements-Roche, MSD: Teerha Piratvisuth. Employment-PROMETRIS GmbH, which has a contract with Roche to provide statistical support: Diethelm Messinger. Employment and stock ownership-Roche: Cynthia Wat. Employment-Roche: Georgios Bakalos. Wan-Long Chuang, Jidong Jia, Kwang-Hyub Han, Tawesak Tanwandee, Deming Tan, Xinyue Chen, Liang Chen, Qing Xie, Joseph Jao-Yiu Sung and Yun-Fan Liaw have no relationships to disclose. Declaration of funding interests: This research was funded by F. Hoffmann-La Roche Ltd., Basel, Switzerland. Support for third-party writing assistance furnished by Blair Jarvis, Health Interactions, was provided by F. Hoffmann-La Roche Ltd., Basel, Switzerland. Publisher Copyright: © 2018 John Wiley & Sons Ltd

PY - 2018/5

Y1 - 2018/5

N2 - Background: In the large randomised NEPTUNE study, peginterferon alfa-2a 180 μg/wk for 48 weeks produced higher hepatitis B e antigen (HBeAg) seroconversion rates 24 weeks post-treatment (36%) than a lower dose (90 μg/wk) and/or shorter duration (24 weeks) (range 14%-26%). Aim: To determine seroconversion rates 5 years after completion of treatment in NEPTUNE. Methods: HBeAg-positive patients who completed 24 weeks’ follow-up in NEPTUNE (with peginterferon alfa-2a 90 μg/wk × 24 weeks [group 1]; 180 μg/wk × 24 weeks [2]; 90 μg/wk × 48 weeks [3] or 180 μg/wk × 48 weeks [4]) were followed up. Results: Three hundred and eighty three of the 544 patients in the original study were enrolled in the long-term follow-up study. Many patients (196 overall; more in groups 1-3 than 4) received nucleos(t)ide analogues or immunomodulators during follow-up, and more patients had missing data at year 5 in groups 2 and 4 (48 weeks, 50/112) than in groups 1 and 3 (24 weeks, 23/103), which confounds the planned per-protocol analysis. HBeAg seroconversion rates in groups 1, 2, 3 and 4 at year 5 were 47.5%, 50.7%, 52.2% and 67.1%, respectively, (odds ratio for group 4 versus 1-3: 2.02; 95% CI 1.21, 3.38), using multiple imputation methods for missing measurements. Conclusion: Seroconversion rates are durable for up to 5 years after completion of peginterferon alfa-2a therapy and, consistent with NEPTUNE, the results suggest that the licensed regimen (180 μg × 48 weeks) is more efficacious for HBeAg-positive patients than a lower dose and/or shorter treatment duration.

AB - Background: In the large randomised NEPTUNE study, peginterferon alfa-2a 180 μg/wk for 48 weeks produced higher hepatitis B e antigen (HBeAg) seroconversion rates 24 weeks post-treatment (36%) than a lower dose (90 μg/wk) and/or shorter duration (24 weeks) (range 14%-26%). Aim: To determine seroconversion rates 5 years after completion of treatment in NEPTUNE. Methods: HBeAg-positive patients who completed 24 weeks’ follow-up in NEPTUNE (with peginterferon alfa-2a 90 μg/wk × 24 weeks [group 1]; 180 μg/wk × 24 weeks [2]; 90 μg/wk × 48 weeks [3] or 180 μg/wk × 48 weeks [4]) were followed up. Results: Three hundred and eighty three of the 544 patients in the original study were enrolled in the long-term follow-up study. Many patients (196 overall; more in groups 1-3 than 4) received nucleos(t)ide analogues or immunomodulators during follow-up, and more patients had missing data at year 5 in groups 2 and 4 (48 weeks, 50/112) than in groups 1 and 3 (24 weeks, 23/103), which confounds the planned per-protocol analysis. HBeAg seroconversion rates in groups 1, 2, 3 and 4 at year 5 were 47.5%, 50.7%, 52.2% and 67.1%, respectively, (odds ratio for group 4 versus 1-3: 2.02; 95% CI 1.21, 3.38), using multiple imputation methods for missing measurements. Conclusion: Seroconversion rates are durable for up to 5 years after completion of peginterferon alfa-2a therapy and, consistent with NEPTUNE, the results suggest that the licensed regimen (180 μg × 48 weeks) is more efficacious for HBeAg-positive patients than a lower dose and/or shorter treatment duration.

UR - http://www.scopus.com/inward/record.url?scp=85043390520&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85043390520&partnerID=8YFLogxK

U2 - 10.1111/apt.14595

DO - 10.1111/apt.14595

M3 - Article

C2 - 29520872

AN - SCOPUS:85043390520

SN - 0269-2813

VL - 47

SP - 1306

EP - 1316

JO - Alimentary Pharmacology and Therapeutics

JF - Alimentary Pharmacology and Therapeutics

IS - 9

ER -