Efficacy of Pegylated Interferon Monotherapy versus Sequential Therapy of Entecavir and Pegylated Interferon in Hepatitis B e Antigen-Positive Hepatitis B Patients: A Randomized, Multicenter, Phase IIIb Open-Label Study (POTENT Study)

Dae Won Jun, Sang Bong Ahn, Tae Yeob Kim, Joo Hyun Sohn, Sang Gyune Kim, Se Whan Lee, Byung Ho Kim, Dong Joon Kim, Ja Kyung Kim, Hyoung Su Kim, Seong Gyu Hwang, Won Choong Choi, Won Young Tak, Heon Ju Lee, Ki Tae Yoon, Byung Cheol Yun, Sung Wook Lee, Soon Koo Baik, Seung Ha Park, Ji Won Park, Sol Ji Park, Ji Sung Lee, Dae Won Jun, Sang Bong Ahn, Tae Yeob Kim, Joo Hyun Sohn, Sang Gyune Kim, Se Whan Lee, Byung Ho Kim, Dong Joon Kim, Ja Kyung Kim, Hyoung Su Kim, Seong Gyu Hwang, Won Choong Choi, Won Young Tak, Heon Ju Lee, Ki Tae Yoon, Byung Cheol Yun, Sung Wook Lee, Soon Koo Baik, Seung Ha Park, Ji Won Park, Sol Ji Park, Ji Sung Lee

Abstract

Background: Until now, various types of combined therapy with nucleotide analogs and pegylated interferon (Peg-INF) in patients with hepatitis B patients have been tried. However, studies regarding the benefits of de novo combination, late-add on, and sequential treatment are very limited. The objective of the current study was to identify the efficacy of sequential treatment of Peg-INF after short-term antiviral treatment.

Methods: Between June 2010 and June 2015, hepatitis B e antigen (HBeAg)-positive patients (n = 162) received Peg-IFN for 48 weeks (mono-treatment group, n = 81) and entecavir (ETV) for 12 weeks with a 48-week course of Peg-IFN starting at week 5 of ETV therapy (sequential treatment group, n = 81). The primary endpoint was HBeAg seroconversion at the end of follow-up period after the 24-week treatment. The primary endpoint was analyzed using Chi-square test, Fisher's exact test, and regression analysis.

Results: HBeAg seroconversion rate (18.2% vs. 18.2%, t = 0.03, P = 1.000) and seroclearance rate (19.7% vs. 19.7%, t = 0.03, P = 1.000) were same in both mono-treatment and sequential treatment groups. The rate of alanine aminotransferase (ALT) normalization (45.5% vs. 54.5%, t = 1.12, P = 0.296) and serum hepatitis B virus (HBV)-DNA <2000 U/L (28.8% vs. 28.8%, t = 0.10, P = 1.000) was not different in sequential and mono-treatment groups at 24 weeks of Peg-INF. Viral response rate (HBeAg seroconversion and serum HBV-DNA <2000 U/L) was not different in the two groups (12.1% vs. 16.7%, t = 1.83, P = 0.457). Baseline HBV-DNA level (7 log10U/ml vs. 7.5 log10U/ml, t = 1.70, P = 0.019) and hepatitis B surface antigen titer (3.6 log10U/ml vs. 4.0 log10U/ml, t = 2.19, P = 0.020) were lower and predictors of responder in mono-treatment and sequential treatment groups, respectively.

Conclusions: The current study shows no differences in HBeAg seroconversion rate, ALT normalization, and HBV-DNA levels between mono-therapy and sequential therapy regimens.

Trial registration: ClinicalTrials.gov, NCT01220596; https://ichgcp.net/clinical-trials-registry/NCT01220596?term=NCT01220596&rank=1.

Keywords: Entecavir; Hepatitis B; Peginterferon Alfa-2a.

Conflict of interest statement

There are no conflicts of interest

Figures

Figure 1
Figure 1
Flow diagram of enrolled patients in the study.
Figure 2
Figure 2
Comparison of HBV DNA level (a) and HBsAg level (b) between sequential therapy and monotherapy groups. HBV: Hepatitis B virus; DNA: Deoxyribonucleic acid; HBsAg: Hepatitis B surface antigen.

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