HBsAg Loss with Peg-interferon Alfa-2a in Hepatitis B Patients with Partial Response to Nucleos(t)ide Analog: New Switch Study

Abstract

Background and Aims: Hepatitis B surface antigen (HBsAg) loss is seldom achieved with nucleos(t)ide analog (NA) therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon (Peg-IFN) alfa-2a. We assessed HBsAg loss with 48- and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA.Methods: Hepatitis B e antigen (HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA <200 IU/mL with previous adefovir, lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48 (n = 153) or 96 weeks (n = 150). The primary endpoint of this study was HBsAg loss at end of treatment. The ClinicalTrials.gov identifier is NCT01464281.Results: At the end of 48 and 96 weeks’ treatment, 14.4% (22/153) and 20.7% (31/150) of patients, respectively, who switched from NA to Peg-IFN alfa-2a cleared HBsAg. Rates were similar irrespective of prior NA or baseline HBeAg seroconversion. Among those who cleared HBsAg by the end of 48 and 96 weeks’ treatment, 77.8% (14/18) and 71.4% (20/28), respectively, sustained HBsAg loss for a further 48 weeks. Baseline HBsAg <1500 IU/mL and week 24 HBsAg <200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48- and 96-week treatment (51.4% and 58.7%, respectively). Importantly, extending treatment from 48 to 96 weeks enabled 48.3% (14/29) more patients to achieve HBsAg loss.Conclusions: Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a. HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks, although the differences in our study cohort were not statistically significant. Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.

Switching to peginterferon for chronic hepatitis B patients with hepatitis B e antigen seroconversion on entecavir – A prospective study

“…Third, we have only included patients who had HBeAg seroconversion on NA. Our results cannot be compared directly to those reported in China, which included patients who have low HBeAg titre and those who have HBeAg loss . Although we believe that HBeAg seroconversion on NA is a better starting point for peginterferon treatment than low HBeAg titre or HBeAg loss, this hypothesis can never be proven by the current study.…”

“…Low HBsAg has been consistently found to be a baseline predictor of response to peginterferon among NA‐treated patients. In studies in China, HBeAg‐negative patients with baseline HBsAg <1500 IU/mL have 22%‐25% chance of losing HBsAg after 1 year of peginterferon treatment . In this study in Hong Kong, patients with baseline HBsAg <1500 IU/mL have 20% chance of developing HBsAg loss, whereas baseline HBsAg <500 IU/mL is the best predictor for HBsAg loss (50%).…”

“…Most patients had HBsAg loss sustained 1 year after stopped peginterferon . Results of another multi‐centre study in China (New Switch Study) also found high HBsAg loss among entecavir‐treated patient with HBeAg loss after switched to peginterferon; 14.4% and 20.7% patients developed sustained HBsAg loss after 48‐ and 96‐week treatment of peginterferon, respectively …”

Effects of pegylated interferon‐α based therapies on functional cure and the risk of hepatocellular carcinoma development in patients with chronic hepatitis B

“…Another randomized, open‐label, phase 4 study conducted in China (NEW SWITCH study) was in patients diagnosed with HBeAg‐positive CHB who had achieved partial responses (HBV DNA < 200 IU/ML and HBeAg loss) after prior NA treatment (ADV, ETV or LAM) for 1‐3 years. The patients were then switched to peg‐IFN‐α‐2a for 48 or 96 weeks (with an initial 12‐week overlap of both the peg‐IFN‐α‐2a and the prior NA used).…”

“…Further analysis of the clinical studies demonstrated that among HBeAg‐positive patients with a low viral load after prior NA therapy, those who had low baseline HBeAg levels (such as HBeAg clearance prior to peg‐IFN‐α treatment and HBsAg levels < 1500 IU/mL or 1000 IU/mL) achieved higher HBsAg loss rates (22.2%‐41.7%) on peg‐IFN‐α treatment.…”