Switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide fumarate (TAF) is safe and effective in patients with chronic hepatitis B (HBV) and was linked to improvements in bone, renal, and kidney function, according to results of several studies presented at the American Association for the Study of Liver Diseases’ The Liver Meeting, held November 8 to 12, 2019, in Boston, Massachusetts.1-3
In a randomized, multicenter, phase 4 study (ClinicalTrials.gov identifier: NCT03241641), researchers assessed whether switching from TDF (300 mg once daily) to TAF (25 mg once daily) may demonstrate better efficacy, safety, and tolerability (including bone and renal outcomes) in patients with chronic HBV who have genotypic resistance to entecavir and/or adefovir.1 Patients receiving TDF monotherapy for at least 96 weeks were randomly assigned in a 1:1 ratio to either switch to TAF or continue on TDF for 48 weeks. The primary efficacy end point was the proportion of patients with HBV DNA <60 IU/mL.
Of 174 eligible patients, 87 switched to TAF and 87 continued on TDF. At week 48, the percentage of patients with HBV DNA <60 IU/mL in TAF group was noninferior to the TDF group (98.9% vs 97.8%; P =.99). In addition, the percentage of patients with normal alanine transaminase (ALT) tended to be higher in the TAF group compared with the TDF group (92.0% vs 79.3%; P =.06). Participants in the TAF group also showed a significantly higher increases in bone mineral density (BMD) at the spine compared with the TDF group (mean percentage change, +1.84% vs 0.08%; P =.01).
Compared with the TDF group, the TAF group also demonstrated a larger increase in estimated glomerular filtration rate as per Cockcroft‐Gault (eGFR) from baseline (mean percentage change, +8.2% vs +4.5%; P =.06).
The improved bone and renal safety as well as increases in eGFR observed in this study was also observed in another study comprising patients with chronic HBV who attained viral suppression with hepatic impairement.2 In this phase 2 study conducted at 18 sites in 7 countries (ClinicalTrials.gov identifier: NCT03180619), 31 patients with chronic HBV who had a Child‐Turcotte‐Pugh score of ≥7 and ≤12 who were virally suppressed for ≥24 weeks and had HBV DNA <20 IU/mL were switched from TDF and/or other antivirals to TAF for 96 weeks.
Week 24 results showed that all patients had HBV DNA <20 IU/mL and a high proportion had normal ALT. Switching to TAF resulted in increases in hip/spine BMD, decreases in bone turnover markers, an increase in eGFR with decreases in tubular markers. Moreover, TAF was well tolerated with only 2 patients having grade 3 or 4 adverse events. There were no serious adverse events related to study drug or discontinuations.
In a real-world cohort study comprised of 103 patients with chronic HBV and chronic kidney disease (CKD) from 9 academic institutions across Canada, switching from TDF to TAF also led to improvements in kidney function, particularly in those with stage 2 CKD.3
Patients were categorized according to their CKD stages using eGFR before switching to TAF and were followed for 104 weeks after initiation of TAF. Of the 103 patients receiving TAF, 81 switched from TDF, 3 switched from another nucleot(s)ide analogue and 14 were nucleot(s)ide analogue-naive.
Among the nucleot(s)ide analogue switch group, HBV‐DNA and hepatitis B surface antigen significantly declined after starting TAF.
There was also a significant increase in eGFR after switching to TAF, a trend that continued after the first year of follow-up (week 0, 74.2; week 52, 75.7; week 104, 77.1; P <.001). Among patients with stage 2 CKD (eGFR 89‐60), eGFR significantly increased after switching compared with pre‐TAF (+0.20 per month; P =.05 vs -0.51 per month; P =.01, respectively).
Switching from TDF to TAF is safe, well tolerated, and effective.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
1. Lim Y-S, Gawk G-Y, Choi J, et al. Tenofovir alafenamide (TAF) for multiple drug‐resistant hepatitis B: a randomized, multicenter trial to evaluate the efficacy and safety of switching from TDF to TAF vs. continuing TDF in CHB patients with genotypic resistance to ETV and/or ADV. Presented at: AASLD: The Liver Meeting; November 8-12, 2019; Boston, MA. Poster 499.
2. Lim Y-S, Lampertico P, Bae HS, et al. Safety and efficacy of switching to tenofovir alafenamide (TAF) in virally suppressed chronic hepatitis B (CHB) patients with hepatic impairment: week 24 results from a phase 2 open‐label study. Presented at: Presented at: AASLD: The Liver Meeting; November 8-12, 2019; Boston, MA. Poster 501.
3. Farag MS, Fung SK, Tam E, et al. Tenofovir alafenamide fumarate is effective and has superior renal safety mainly among stage 2 chronic kidney disease (CKD): real‐world study from the Canadian Hepatitis B Network (CANHEPB). Presented at: Presented at: AASLD: The Liver Meeting; November 8-12, 2019; Boston, MA. Poster 481.