Switching to TAF helps improve virologic response in HBV patients in real world

Switching to tenofovir alafenamide (TAF) from nucleos(t)ide analogue therapies was associated with improved virologic response and liver function in patients with chronic hepatitis B virus (HBV) infection, even in those with decompensated HBV cirrhosis, according to real-world studies presented at AASLD 2021.

TAF, a new prodrug of tenofovir, provides more efficient incorporation and conversion of tenofovir intracellularly at a relatively lower dose than tenofovir disoproxil fumarate (TDF) — and hence is expected to confer a better safety profile while maintaining similar efficacy.

The first study used data from 504 treatment-experienced chronic HBV patients (median age 54 years, 59.1 percent male) across 15 cities in Turkey, who switched to TAF. Most of them were previously treated with TDF (83.9 percent), while the rest took entecavir (6.9 percent), lamivudine (5.6 percent), telbivudine (2.8 percent), or adefovir (0.8 percent), over a median duration of 52 months. [AASLD 2021, abstract 810]

The most common indication for switching was osteoporosis (40.7 percent), followed by altered blood phosphate level (21.0 percent), use of drug affecting bone mineral density (11.7 percent), and reduced glomerular filtration rate (12.1 percent).

The proportion of patients who achieved viral DNA suppression (HBV DNA <20 IU/mL) grew from 79.4 percent at baseline (during switch) to 90.2 percent at 6 months and 87.0 percent at 12 months after switching to TAF.

Normalization of the liver enzyme ALT was also seen in increasingly more patients over time, from 72.3 percent at baseline to 79.1 percent at 6 months and 80.0 percent at 12 months after switching.

“Although the majority of the patients were using potent nucleos(t)ide analogues, switching to TAF was associated with improved virologic and biochemical responses,” said presenting author Dr Fehmi Tabak from Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey.

“Renal functions remained stable and the drug was well tolerated,” he reported. The levels of estimated GFR were constant from baseline (94 mL/min) to 6 and 12 months (90.0 mL/min and 86.9 mL/min, respectively) after switching. Common side effects included headache (6.5 percent), nausea (3.2 percent), fatigue (3.2 percent), and rash (1.0 percent).

“Real-life data confirmed the efficacy and safety of TAF in treatment-experienced HBV patients,” Tabak concluded.

Not only this, the benefit of switching appeared to extend to even patients with decompensated HBV cirrhosis in another real-world study.

The prospective cohort study followed 56 patients with decompensated HBV cirrhosis who had switched to TAF monotherapy due to poor response to nucleos(t)ide analogue therapy or low-level viraemia (LLV) for at least 6 months. [AASLD 2021, abstract 824]

At 48 weeks, the rate of complete virologic response (CVR) in patients with decompensated HBV cirrhosis who switched to TAF significantly increased compared with that at 12 weeks (80.00 percent vs 32.14 percent; p<0.05).

The CVR benefit appeared to be more pronounced at 12 weeks in the subgroup of patients with LLV (HBV DNA <2,000 IU/mL) compared with the subgroup with poor response (HBV DNA ≥2,000 IU/mL; 61.54 percent vs 6.67 percent). Nonetheless, the difference between the two groups was not statistically different at 24, 36, and 48 weeks.

In addition, improvements in liver function were also seen — as reflected in significant increased rate of ALT normalization (95 percent vs 66.07 percent; p<0.05) and better Child-Pugh score (mean, 5.45 vs 8.66; p<0.05) at 48 weeks compared with baseline.

“Switching to TAF monotherapy for patients with decompensated hepatitis B cirrhosis due to poor response to nucleos(t)ide analogue therapy/LLV is effective [with] regard [to] both CVR and liver function benefits,” the researchers stated.