Switch From Entecavir to Tenofovir Alafenamide Safe and Effective for Hepatitis B

The complete viral suppression (CVS) rate in patients with hepatitis B virus (HBV) infection was found to increase from 91.9% to 97.2% 96 weeks after switching from entecavir (ETV) to tenofovir alafenamide (TAF), according to the results of a study published in The American Journal of Gastroenterology.

Both ETV and TAF are first-line treatments for HBV, but data associated with switching from long-time ETV to TAF are limited. In this study, 425 patients with chronic HBV treated with ETV for at least 12 months were switched to TAF. The patients were located in the United States, Korea, Japan, and Taiwan. Mean duration of ETV treatment prior to switching was 6.16±3.17 years. 

Approximately half of the patients (55.6%) had stage 1 chronic kidney disease (CKD); 35.7% had stage 2 CKD and 8.8% had stage 3-5 CKD. Mean baseline estimated glomerular filtration rate (eGFR) was 89±19 mL/min/1.73 m².

After switching from ETV to TAF, the rate of CVS increased significantly; CVS was 95.3% (385/404; P = .05) at 24 weeks, 97.0% (288/297; P = .01) at 72 weeks, and 97.2% (174/179; P = .02) at 96 weeks. Approximately half of the patients who were not virally suppressed prior to switching achieved CVS at 48 weeks. The trend of increasing CVS rates was significant (P < .001) as was the trend of decreasing mean HBV DNA (P < .001). There was, however, no change in either the rate of alanine aminotransferase (ALT) normalization (P = .48) or mean ALT level (P = .97).

There were no significant changes in CKD stage over time. At week 96, 11% (26/235) of patients with stage 1 CKD moved to stage 2, and 8% (12/151) of patients with stage 2 CKD moved to stage 3 or higher. Improvement in stage of CKD was seen with 18% (27/151) of patients with stage 2 to improving to stage 1, and 19% (7/37) moving from stage 3-5 to stage 2. No overall change in mean eGFR was reported following adjustment for age, sex, diabetes, hypertension, and cirrhosis.

Factors that predicted change in eGFR were age (P < .001) and baseline eGFR of either 60 to 89 mL/min/1.73 m² (P < .001) or <60 mL/min/1.73 m² (P < .001). Using logistic regression, worsening CKD was associate with baseline eGFR only (adjusted odds ratio: 0.96; 95% CI 0.94-0.99; P = .002).

The investigators highlighted several study limitations including missing data due to the retrospective nature of the study and no understanding of patient experience, adherence, or reason for the switch. The study also lacked a control arm, and the cohort was not closed (ie, not everyone reached the 96-week endpoint). The study was strengthened by the use of real-life data, treatment-naive patients receiving ETV, and long-term follow-up including several analysis and subanalysis.

The investigators concluded that rate of CVS and HBV DNA and surface antigen levels improved during the switch from ETV to TAF, with no significant change in renal function. Although the switch appears to be safe and effective, they caution that due to the size of the incremental changes, the costs and benefits must be assessed before automatically switching these regimens. The investigators further recommended additional studies examining the long-term effects of treatment with TAF.

Disclosures

The study was supported by an investigator-initiated grant from Gilead Sciences. For full disclosure details, please refer to the original reference.

Reference

Nguyen MH, Atsukawa M, Ishikawa T, et al. Outcomes of sequential therapy with tenofovir alafenamide after long-term entecavir. Am J Gastroenterol. Published online February 2, 2021. doi:10.14309/ajg.0000000000001157