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)

摘要

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 log10 U/ml vs.7.5 log10 U/ml,t =1.70,P =0.019) and hepatitis B surface antigen titer (3.6 log10 U/ml vs.4.0 log10 U/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://clinicaltrials.gov/ct2/show/NCT01220596?term=NCT01220596&rank=1.