The efficacy and safety of adding on or switching to peginterferon α-2b in HBeAg-positive chronic hepatitis B patients with long-term entecavir treatment: A multicentre randomised controlled trial
Qiankun Hu 1 , Xun Qi 1 , Yiqi Yu 2 , Yueqiu Gao 3 , Xinxin Zhang 4 , Qianqian Wang 1 , Xueyun Zhang 2 , Yunhui Zhuo 3 , Jing Li 4 , Jiming Zhang 2 , Liang Chen 1 , Yuxian Huang 1 2
Affiliations
Affiliations
1
Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
2
Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
3
Department of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
4
Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
PMID: 36128636 DOI: 10.1111/apt.17222
Abstract
Background & aims: The strategies of adding on or switching to peginterferon (PEG-IFN) therapy improved the serological response rates in nucleos(t)ide analogues experienced chronic hepatitis B (CHB) patients. However, robust data on which combination strategy is more effective remain lacking.
Methods: In this multicentre, parallel, open-label, randomised, controlled trial, HBeAg-positive CHB patients with entecavir (ETV) treatment ≥2 years, hepatitis B surface antigen (HBsAg) <3000 IU/ml, HBeAg <200S/CO and HBV DNA <50 IU/ml were randomly assigned in a 1:1:1 ratio to add on PEG-IFN (add-on), switch to PEG-IFN (switch-to) or continue ETV monotherapy for 48 weeks. The primary endpoint was HBeAg seroconversion at week 48.
Results: A total of 153 patients were randomised into three treatment arms (50 in add-on, 52 in switch-to and 51 in monotherapy). Compared with continuous ETV monotherapy, both add-on and switch-to strategies achieved higher rates of HBeAg seroconversion (18.0% vs. 2.0%, p = 0.007; 19.2% vs. 2.0%, p = 0.005, respectively), HBeAg loss (24.0% vs. 5.9%, p = 0.010; 23.1% vs. 5.9%, p = 0.013, respectively), HBsAg < 100 IU/ml (30.0% vs. 0%, p < 0.001; 34.6% vs. 0%, p < 0.001, respectively), and higher HBsAg reduction (-0.90 vs. -0.06 log10 IU/ml, p < 0.001; -0.92 vs. -0.06 log10 IU/ml, p < 0.001, respectively) at week 48. The efficacy was comparable between add-on and switch-to arms (p > 0.05). Adverse events were mainly related to PEG-IFN but generally tolerable.
Conclusion: In CHB patients who achieved virological response with long-term ETV treatment, both adding on and switching to PEG-IFN therapy are alternative strategies to result in higher rates of HBeAg seroconversion and higher HBsAg reduction compared with continuous ETV monotherapy.
Clinical trials registration: Chinese Clinical Trial Registry (www.chictr.org.cn, identifier: ChiCTR-IPR-17012055).