Efficacy and Safety of Peginterferon Alfa‐2a (40KD) in Children With Chronic Hepatitis B: The PEG‐B‐ACTIVE Study

Abstract

Children with chronic hepatitis B (CHB) represent an area of unmet medical need, attributed to increased lifetime risk of CHB sequelae and limited therapeutic options compared with adult CHB patients. The PEG-B-ACTIVE (NCT01519960) phase III study evaluated peginterferon (PegIFN) alfa-2a treatment in children aged 3 to <18 years with CHB. A total of 161 hepatitis B e antigen (HBeAg)-positive immune-active patients without advanced fibrosis (AF)/cirrhosis were randomized (2:1) to PegIFN alfa-2a (Group A, n = 101) or no treatment (Group B, n = 50); patients with AF were assigned to PegIFN alfa-2a (Group C, n = 10). PegIFN alfa-2a was administered for 48 weeks by body surface area (BSA) category, based on 180 μg/1.73 m . HBeAg seroconversion rates at 24 weeks posttreatment were significantly higher in Group A (25.7% vs. 6%; P = 0.0043), as were the rates of hepatitis B surface antigen (HBsAg) clearance (8.9% vs. 0%; P = 0.03), hepatitis B virus (HBV) DNA <2,000 IU/mL (28.7% vs. 2.0%; P < 0.001) or undetectable (16.8% vs. 2.0%; P = 0.0069), and alanine aminotransferase (ALT) normalization (51.5% vs. 12%; P < 0.001). Safety, including incidence of ALT flares and neutropenia, was comparable to the established PegIFN alfa-2a profile in HBV-infected adults or hepatitis C virus-infected children. Changes in growth parameters were minimal during treatment and comparable to those in untreated patients. Safety and efficacy outcomes in Group C were in line with Group A. Conclusion: PegIFN alfa-2a treatment of children in the immune-active phase of CHB was efficacious and well tolerated, and associated with higher incidence of HBsAg clearance than in adults. This represents an important advance to the treatment options for children with CHB.

Long‐term efficacy and safety of peginterferon in the treatment of children with HBeAg‐positive chronic hepatitis B

“…The phase III of the clinical study on PegIFNα‐2a for antiviral treatment in children with CHB showed that children had higher HBsAg clearance rate after drug discontinuation than did adults (8.9% vs 3%) when treated with PegIFNα‐2a. Zhu et al reported the efficacy of PegIFNα‐2a in the treatment of 45 cases of Chinese children with HBeAg‐positive CHB (96 weeks), and the 96‐week HBeAg and HBsAg seroconversion rates were 91.9% and 18.9%, respectively.…”

“…There are relatively fewer reports on predictors for efficacy in children. Phase III clinical trials on children treated with PegIFNα‐2a found that the efficacy was better among patients with baseline ALT of 2‐5 ULN than among those with baseline ALT of 5‐10 ULN. Multivariate regression analysis for the present study showed that genotype B ( P = 0.0135), body weight < 25 kg ( P = 0.0369) or between 25 kg and 45 kg ( P = 0.0260) and decrease in HBsAg level by >1 log ( P < 0.0001) after 24 weeks of treatment were independent predictors for HBsAg clearance at the end of the follow‐up.…”

“…In 2017, the United States of America and the European Union approved successively the use of peginterferon alpha‐2a (PegIFNα‐2a) for CHB patients over 3 years of age. Although the indication has not been approved in China, the results of the phase III clinical trial showed the HBeAg conversion rate of 25.7% and HBsAg conversion rate of 8.9% at week 24 after drug discontinuation . This study aimed to further explore the efficacy of PegIFNα‐2a as an antiviral treatment in Chinese children and analyse the long‐term follow‐up after drug discontinuation.…”

Interferon alpha treatment leads to a high rate of hepatitis B surface antigen seroconversion in Chinese children with chronic hepatitis B

“…Alternatively, IFNa can achieve a functional cure in adults without generating any drug resistance, although the efficacy is low at below 5% . However, the efficacy of IFNa treatment has only been tested in children with CHB recently …”

“…Complicating this issue is that paediatric patients usually show normal ALT levels even when in the active immune stage as defined by liver biopsies . In a recent study evaluating the efficacy and safety of PEG‐IFNa in children with CHB, young patients with ALT levels <2‐fold the ULN also achieved hepatitis B e antigen (HBeAg) seroconversion after IFNa treatment . This further suggested that the current guideline for IFNa treatment, which is mainly based on observations from adult CHB patients, needs to be reexamined.…”