Clinical trial: An open‐label, randomised trial of different re‐start strategies after treatment withdrawal in HBeAg negative chronic hepatitis B

• Published in: Alimentary pharmacology & therapeutics 2024-08, Vol.60 (4), p.434-445
• Main Authors: Johannessen, Asgeir, Reikvam, Dag Henrik, Aleman, Soo, Berhe, Nega, Weis, Nina, Desalegn, Hailemichael, Stenstad, Tore, Heggelund, Lars, Samuelsen, Ellen, Karlsen, Lars Normann, Lindahl, Karin, Pettersen, Frank Olav, Iversen, Jonas, Kleppa, Elisabeth, Bollerup, Signe, Winckelmann, Anni Assing, Brugger‐Synnes, Pascal, Simonsen, Hans Erling, Svendsen, Jan, Kran, Anne‐Marte Bakken, Holmberg, Marte, Olsen, Inge Christoffer, Rueegg, Corina Silvia, Dalgard, Olav
• Format: Article
• Language: English
• Subjects: Antiviral agents; Clinical trials; Hepatitis; Hepatitis B; Hepatitis B e antigen; Hepatitis B surface antigen; Immune response; Patients; Statistical analysis
• ISSN: 0269-2813; 1365-2036; 1365-2036
• DOI: 10.1111/apt.18147

Summary Background Stopping nucleos(t)ide analogue (NA) therapy in patients with chronic hepatitis B (CHB) may trigger a beneficial immune response leading to HBsAg loss, but clinical trials on re‐start strategies are lacking. Aim To assess whether it is beneficial to undergo a prolonged flare after NA cessation. Methods One‐hundred‐and‐twenty‐seven patients with HBeAg negative, non‐cirrhotic CHB with at least 24 months of viral suppression on NA therapy were included. All study participants stopped antiviral therapy and were randomised to either low‐threshold (ALT > 80 U/L and HBV DNA > 2000 IU/mL) or high‐threshold (ALT > 100 U/L for >4 months, or ALT > 400 U/L for >2 months) for the re‐start of therapy. The primary endpoint was HBsAg loss within 36 months of stopping antiviral treatment. The primary analysis was based on intention‐to‐treat allocation with last observation carried forward. Results There was a numerical but not statistically significant difference in HBsAg loss between the low‐threshold (3 of 64; 4.7%) and the high‐threshold (8 of 63; 12.7%) group (risk difference: 8.0%, 95% CI: −2.3 to 19.6, p = 0.123). None of the patients with end‐of‐treatment HBsAg > 1000 IU/mL achieved HBsAg loss; among those with end‐of‐treatment HBsAg