Chronic hepatitis B patients who discontinued tenofovir disoproxil fumarate (TDF, Viread) after achieving viral suppression had higher rates of clinical relapse compared to those who stopped entecavir, a global retrospective study found.

At 6 and 24 months, clinical relapse rates after stopping TDF grew from 31% to 58%, which was significantly higher than after entecavir cessation (11% and 44% for the two time points respectively, P<0.001), reported Harry Janssen, MD, PhD, of the Erasmus MC University Medical Center in Rotterdam, The Netherlands, and colleagues from the RETRACT-B study group.

In the study of 1,402 patients who discontinued either of the two treatments after viral suppression, hepatitis B surface antigen (HBsAg) loss occurred in 6.8% over 18 months of off-treatment follow-up, with no significant differences between the TDF and entecavir groups, according to the findings in Clinical Gastroenterology and Hepatology.

Both agents are recommended in international guidelines as first-line treatments in chronic hepatitis B, have good safety profiles, and have shown comparable rates of viral suppression, according to Janssen and co-authors.

“Over the past decade, there has been strong interest in understanding whether one drug is superior to the other in terms of preventing or delaying [hepatocellular carcinoma] HCC development or viral relapse following treatment discontinuation,” the group noted.

While virologic relapse rates were initially higher in the TDF group (65% vs 42% in the entecavir group at 6 months), they converged over time (83% vs 79% at 24 months). And retreatment rates (48% overall) were also similar between groups.

Janssen’s group suggested that finite therapy could be considered with either entecavir or TDF, with evidence remaining insufficient to prefer one drug over the other. But they cautioned that in their study, virological relapses accompanied by alanine transaminase (ALT) elevations occurred earlier in patients who stopped TDF, and these patients had higher peak ALT levels during clinical relapse.

“In this regard, closer off-therapy monitoring may be required early after TDF discontinuation to ensure continued safety, with an option to use [entecavir] prior to stopping therapy in patients with a history of or current advanced fibrosis,” they noted.

“The concept of finite therapy has emerged due to concerns regarding cost, adherence, and safety, and some studies have demonstrated potential for sustained disease remission following treatment discontinuation,” the group explained. “Nonetheless, [nucleos(t)ide analogues] withdrawal requires caution, as virological relapse and severe ALT flares are frequently observed post-treatment, which could lead to hepatic decompensation.”

For their study, the researchers examined data on 1,402 chronic hepatitis B patients who discontinued treatment with either entecavir (n=981) or TDF (n=421) after achieving undetectable serum levels of hepatitis B virus (HBV) DNA. Patients were treated from 2001 to 2020 across 13 centers in Asia, North America, and Europe.

Virological relapse was defined as a single elevation of HBV DNA ≥2,000 IU/mL, while clinical relapse included the detection of ALT levels at twice the upper limit of normal during a clinical visit.

Patients in both groups had similar baseline and clinical characteristics: median age was 54 years, about three-quarters were men, and 93-94% were Asian.

Longer duration of entecavir or TDF treatment and lower HBsAg levels by the end of therapy were significantly associated with HBsAg loss.

The authors acknowledged limitations to the data. HBV genotypes remained unknown for most patients, since they were on long-term antiviral therapy, and the researchers were not able to compare kinetics of viral markers.

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