The following is a summary of “Randomized Trial of Tenofovir With or Without Peginterferon Alfa Followed by Protocolized Treatment Withdrawal in Adults With Chronic Hepatitis B,” published in the July 2023 issue of Gastroenterology and Nutrition by Terrault, et al.
The goal of achieving hepatitis B surface antigen (HBsAg) loss is important in treating chronic hepatitis B, but current monotherapies have limited success in achieving this outcome. For a study, researchers sought to investigate whether combination strategies, including treatment withdrawal, could improve the rate of HBsAg loss. Additionally, they aimed to assess the association of HBsAg clearance with various factors.
A total of 201 participants (52% HBeAg positive, 12%/6% genotype A/A2, 7% cirrhosis) were enrolled in a randomized trial and assigned in a 1:1 ratio to receive either tenofovir disoproxil fumarate (TDF) with peginterferon (PegIFN) alfa-2a for the first 24 weeks, followed by TDF alone, or TDF alone. The study’s primary endpoint was the rate of HBsAg loss at week 240.
At the end of the treatment phase (week 192), HBsAg loss was observed in 5.3% of participants in the combination TDF + PegIFN (n = 102) group and 1.0% in the TDF alone group (n = 99). Although the difference was not statistically significant (P = 0.09), it suggested a trend toward higher HBsAg loss in the combination group. By week 240, 9 participants had cleared HBsAg, with 5.3% in the combination group and 4.1% in the TDF alone group, showing no significant difference (P = 0.73). Notably, participants in the combination group experienced earlier HBsAg decline and loss compared to the TDF alone group, with 28% of the combination group achieving a ≥1-logIU/mL decline in quantitative HBsAg by week 24, compared to 6% in the TDF alone group (P = 0.04).
The combination of PegIFN with TDF followed by TDF withdrawal, did not significantly increase the overall rate of HBsAg clearance. However, it did lead to earlier HBsAg decline, indicating a potential benefit of combination therapy. Furthermore, the analysis revealed that pretreatment HBeAg positivity and subgenotype A2 of the hepatitis B virus was strongly associated with HBsAg clearance, with higher rates observed in HBeAg-positive individuals (8.6%) compared to HBeAg-negative individuals (1.1%). The findings provided valuable insights into the factors influencing HBsAg clearance in chronic hepatitis B treatment.
Source: journals.lww.com/ajg/Abstract/2023/07000/Randomized_Trial_of_Tenofovir_With_or_Without.22.aspx