Eight-Year Study Confirms Long-Term Safety and Efficacy of Tenofovir Alafenamide for Chronic Hepatitis B in Chinese Patients
核心洞察
An eight-year Phase 3 study in Chinese patients with chronic hepatitis B demonstrated that tenofovir alafenamide (TAF) maintained high viral suppression rates of approximately 95% while preserving renal and bone safety.
Patients who switched from tenofovir disoproxil fumarate (TDF) to TAF showed improvement in renal and bone parameters that had declined during TDF treatment, suggesting reversibility of these side effects.
No resistance to TAF was detected throughout the eight-year study period, reinforcing its role as a preferred long-term treatment option for the aging chronic hepatitis B population in China.
An eight-year Phase 3 study has provided robust evidence supporting tenofovir alafenamide (TAF) as a superior long-term treatment option for chronic hepatitis B (CHB) in Chinese patients, demonstrating sustained efficacy while maintaining improved renal and bone safety compared to tenofovir disoproxil fumarate (TDF). The findings, recently published in the Journal of Clinical and Translational Hepatology, represent the longest investigation of TAF in this population.
Study Design and Participants
The study enrolled 334 Chinese participants with chronic hepatitis B from two Phase 3 trials. After completing a three-year double-blind phase, participants were eligible to receive open-label TAF 25 mg daily for up to an additional five years. Among the participants, 212 of 227 originally randomized to TAF continued treatment (TAF-TAF group), while 99 of 107 participants initially on TDF switched to open-label TAF (TDF-TAF group).
Sustained Viral Suppression
At Year 8, both treatment groups demonstrated comparable viral suppression rates. Using an intent-to-treat analysis with missing data counted as treatment failure, 79.3% (180/227) of participants in the TAF-TAF group and 78.5% (84/107) in the TDF-TAF group achieved viral suppression, defined as HBV DNA levels below 29 IU/mL. When excluding missing data from the analysis, viral suppression rates increased substantially to 95.2% (180/189) and 95.5% (84/88) for the TAF-TAF and TDF-TAF groups, respectively.
Alanine aminotransferase normalization rates remained high and comparable between both groups throughout the study period. Serologic response rates continued to increase over time, with higher rates observed in the TAF-TAF group compared to those who switched from TDF.
Improved Safety Profile
The study revealed significant safety advantages for TAF, particularly regarding renal and bone health. Estimated glomerular filtration rate and hip/spine bone mineral density remained stable in the TAF-TAF group throughout the eight-year period. Notably, participants who experienced small declines in renal and bone parameters during double-blind TDF treatment showed improvement in these measures after switching to open-label TAF, suggesting that TDF-associated adverse effects may be reversible.
Resistance Surveillance
Throughout the eight-year study period, no resistance to TAF was detected in any participant, reinforcing the drug's genetic barrier to resistance and supporting its use for long-term treatment.
Clinical Implications
The researchers concluded that this eight-year analysis provides robust evidence supporting the long-term efficacy and safety of TAF in Chinese patients with chronic hepatitis B. The findings are particularly relevant for the aging CHB population in China, where long-term treatment safety becomes increasingly important. The study reinforces TAF's role as the preferred long-term treatment option, offering comparable efficacy to TDF while providing superior renal and bone safety profiles.
The reversibility of TDF-associated renal and bone parameter declines after switching to TAF represents a significant clinical finding, suggesting that patients currently on TDF may benefit from transitioning to TAF to preserve long-term organ function.