Real-world studies demonstrate TAF efficacy and safety in chronic hep B

Treatment with tenofovir alafenamide (TAF) results in similar virological response compared with tenofovir disoproxil fumarate (TDF) in treatment-naïve patients with chronic hepatitis B (CHB), according to a real-world study from Korea presented at ILC 2022.

Researchers from the Asan Medical Center, University of Ulsan College of Medicine in Seoul, South Korea, identified 2,747 treatment-naïve patients (mean age 48.6 years, 58.2 percent male) with CHB. Of these, 502 and 2,245 patients were being treated with TAF and TDF, respectively. One-third of patients (33.3 percent) had cirrhosis.

Virological response, defined as hepatitis B virus (HBV) DNA <15 IU/mL, was achieved by 70.3, 81.2, and 83.3 percent of TAF recipients at 12, 24, and 36 months, respectively, compared with 67.9, 84.3, and 86.1 percent of TDF recipients at those respective timepoints (p>0.05 for all). [ILC 2022, abstract SAT378]

On-treatment normalization of alanine aminotransferase (ALT) levels (<40 U/L) was documented in 79.7, 90.6, and 86.2 percent of TAF recipients and 78.2, 85.8, and 85.7 percent of TDF recipients at 12, 24, and 36, months, respectively (p>0.05 for all).

The risk of hepatocellular carcinoma (HCC) was comparable between patients on TAF and TDF, both in the overall population (0.80 vs 1.45 per 100 person-years; p=0.30) and in the propensity score-matched population comprising 495 pairs (0.82 vs 0.90 per 100 person-years; p=0.60).

Increase in serum creatinine levels from baseline during the early part of the study was lower among TAF vs TDF recipients. There were significant decreases in total cholesterol, triglyceride, and HDL-cholesterol levels, but not LDL-cholesterol levels, with TDF vs TAF.

“Real-world data indicate that TAF has comparable efficacies to TDF in terms of virological response and ALT normalization, with no higher risk of HCC,” the authors said.

Safety in patients with renal or bone disorders

In another real-world study, this time conducted in Greece, the safety and efficacy of TAF at 2 years was confirmed among patients with renal and bone disorders. [ILC 2022, abstract SAT374]

Participants in the HERACLIS-TAF study were 176 adults (mean age 64 years, 71 percent male) with CHB who initiated treatment with TAF between February 2018 and October 2019 at 13 tertiary liver clinics in the study registry. Patients with hepatitis D virus co-infection or active malignancy and those with exposure to bisphosphonates in the prior 6 months were excluded.

Eighty-five percent of patients had undetectable HBV DNA levels, 86 percent had ALT levels <40 IU/L, and 45 percent had estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m². Ninety-four percent of patients had prior exposure to nucleos(t)ide analogues (NAs), with 91 percent having directly switched from another NA to TAF and 81 percent switching from TDF.

HBV DNA levels were undetectable in 97 and 100 percent of patients at 12 and 24 months, respectively, while ALT levels were ≤40 IU/L in 96 and 95 percent of patients, respectively.

Among patients who switched from other NAs to TAF, there were significant reductions in median ALT levels between baseline (23 IU/L) and 12 and 24 months of TAF treatment (20 IU/L at both time points; p<0.001).

Mean eGFR levels reduced from 74 mL/min/1.73 m² at initiation of other NAs to 66 mL/min/1.73 m² at TAF initiation (p<0.001), then increased to 69 and 71 mL/min/1.73 m² (p=0.001 and p<0.001, respectively) at 6 and 12 months of TAF treatment, respectively, remaining stable at 71 mL/min/1.73 m² at 24 months.

Among the 38 patients with phosphate levels <2.5 mg/dL at TAF initiation, there were also significant increases in serum phosphate levels between TAF initiation and 12 and 24 months (mean 2.1, 2.7, and 2.9 mg/dL, respectively; p<0.001).

There was no significant difference in bone mineral density (BMD), as per hip T-score, between TAF initiation and 12 months (mean -2.2 vs -2.1; p=0.157), though there was a significant increase at 24 months (mean -1.9; p=0.001).

No TAF-related serious adverse events (AEs) or AE-related discontinuations were documented.

“In the phase III trials in CHB, TAF compared to TDF had similar efficacy and improved safety in renal function and BMD parameters, but patients with significant renal or BMD disorders were not included,” said the researchers.

“[The results of this study showed that] in most NA-experienced CHB patients with renal and/or BMD disorders/risks, 2-year TAF therapy is safe and effective [at] achieving or maintaining virological suppression and improving ALT, eGFR, and serum phosphate levels,” they concluded.