Switching to Besifovir in chronic hepatitis B patients receiving Tenofovir Disoproxil Fumarate: 96 weeks results of phase 4 trial

초록

Background and aims: In the previous 48-week phase 4 study, switching from TDF to BSV therapy contributed to the maintenance of antiviral effects and improved bone and renal safety in patients with virologically-suppressed CHB. We evaluated longer-term outcomes in CHB patients in the extended follow-up of the study. Method: After 48 weeks of comparison of BSV with TDF, eligible patients who had agreed with participating in the extended study continued or switched to either of the drugs, and were followed-up to 96 weeks. We analyzed antiviral efficacy as well as bone and renal safety for the 4 groups. Results: Among 130 patients who received randomized treatments, 101 patients were included for this observational study (BSV-BSV group, 5; BSV-TDF group, 46; TDF-BSV group, 4; TDF-TDF group, 46). At 96 weeks, 100.0% of patients in the BSV-BSV and TDF-BSV group, and 97.8% in the BSV-TDF and TDF-TDF group maintained virologic response (HBV DNA <20 IU/ml) (p = 1.00). Biochemical and serologic responses were comparable between the groups. Of note, bone turnover biomarkers were significantly improved in the BSV-BSV and TDF-BSV groups, and were worsened in the BSV-TDF and TDF-TDF group; accordingly, spine BMD increased in the BSV-BSV and TDFBSV group, and decreased in the BSV-TDF and TDF-TDF group (% changes; 1.67 ± 1.68, 3.17 ± 4.31, −1.35 ± 3.98, −0.20 ± 3.91, respectively). The mean %changes of estimated glomerular filtration rates improved in the TDF-BSV group (2.29 ± 9.93%) while those decreased in the BSV-TDF group (−2.97 ± 10.40%). There were no adverse events in the BSV-BSV and TDF-BSV groups from 48 to 96 weeks while there were three in the TDF-TDF and BSV-TDF groups. Conclusion: In this extensional study, antiviral efficacies were comparable between the groups at 96 weeks. Patients receiving BSV for up to 96 weeks showed improved bone and renal safety after the completion of 48 weeks of BSV or TDF therapy in virologicallysuppressed CHB patients.