Treatment and Renal Outcomes Up to 96 Weeks After Tenofovir Alafenamide Switch From Tenofovir Disoproxil Fumarate in Routine Practice

Abstract

BaCKgRoUND aND aIMS: Real-world data for treatment effectiveness and renal outcomes in chronic hepatitis B (CHB) patients who were switched to the new and safer prodrug tenofovir alafenamide (TAF) from tenofovir disoproxil fumarate (TDF) are limited. Therefore, we aimed to evaluate treatment and renal outcomes of this population. appRoaCH aND ReSUltS:We analyzed 834 patients with CHB previously treated with TDF for ≥12 months who were switched to TAF in routine practice at 13 US and Asian centers for changes in viral (HBV DNA < 20 IU/mL), biochemical (alanine aminotransferase [ALT] < 35/25 U/L for male/female), and complete (viral+biochemical) responses, as well as estimated glomerular filtration rate (eGFR; milliliters per minute per 1.73 square meters) up to 96 weeks after switch. Viral suppression (P < 0.001) and ALT normalization (P = 0.003) rates increased significantly after switch, with a trend for increasing complete response (P trend = 0.004), while the eGFR trend (P trend > 0.44) or mean eGFR (P > 0.83, adjusted for age, sex, baseline eGFR, and diabetes, hypertension, or cirrhosis by generalized linear modeling) remained stable. However, among those with baseline eGFR < 90 (chronic kidney disease [CKD] stage ≥2), mean eGFR decreased significantly while on TDF (P = 0.029) but not after TAF switch (P = 0.90). By week 96, 21% (55/267) of patients with CKD stage 2 at switch improved to stage 1 and 35% (30/85) of CKD stage 3-5 patients improved to stage 2 and 1.2% (1/85) to stage 1.CoNClUSIoNS: Overall, we observed continued improvement in virologic response, ALT normalization, and no significant changes in eGFR following switch to TAF from TDF.

Real-world experience of switching from tenofovir disoproxil fumarate to tenofovir alafenamide in patients with chronic hepatitis B: a retrospective study

“…TAF increased the ALT normalization rate according to the American Association for the Study of Liver Diseases (AASLD) criteria in the three randomized trials ( Lampertico et al, 2020 ; Agarwal et al, 2018 ). Recently, three retrospective studies in patients with CHB showed similar findings at 12 to 18 months after switching to TAF, but one study showed that the change was not significant at 6 months after switching to TAF ( Toyoda et al, 2021 ; Bernstein et al, 2021 ; Farag et al, 2021 ; Alghamdi et al, 2020 ). Our study showed that the decrease in ALT level persisted after switching to TAF, but the ALT normalization rate was similar at the time of switching and 48 weeks after switching.…”

“…TAF is a prodrug of tenofovir (TFV) that has less renal toxicity than TDF. The renal function of patients stabilized at 48 weeks after switching to TAF in a randomized trial and four retrospective studies ( Lampertico et al, 2020 ; Toyoda et al, 2021 ; Bernstein et al, 2021 ; Farag et al, 2021 ; Alghamdi et al, 2020 ). The renal outcome was similar in our study in that the median eGFR decreased during TDF therapy (100.09 vs 91.97 mL/min/1.73 m²) and stabilized at 48 weeks after switching to TAF (93.47 mL/min/1.73 m²).…”

Renal safety and biochemical changes for 2 years after switching to tenofovir alafenamide from long‐term other nucleotide analog treatment in patients with chronic hepatitis B

“…The recent report also indicated that ALT normalization increased after switching from TDF to TAF. 27 This result seems to suggest that other factors contribute to the abnormality of ALT during TDF treatment, except This study had a few limitations. First, the treatment regimens before switching to TAF were heterogeneous.…”

Review article: switching patients with chronic hepatitis B to tenofovir alafenamide—a review of current data

“…In the Phase 3 TDF to TAF switch study, the proportion of patients with at least one CKD stage improvement was significantly higher in TAF‐treated patients compared with TDF‐treated patients (25% vs 8%, P < 0.0001), and the proportion of patients with at least one CKD stage worsening was significantly higher in TDF‐treated patients compared with TAF‐treated patients (14% vs 6%, P < 0.0001) 36 . In a retrospective analysis of switching, patients with reduced eGFR (<90 ml/min) at baseline had significant decreases in eGFR while on TDF, but not after TAF switch 51 . After Week 96 of switching to TAF, approximately one‐fifth of patients with mildly decreased eGFR (60–89 ml/min) improved to normal range, and approximately one‐third of patients with moderately decreased eGFR (below 60 ml/min) improved to eGFR 60–89 ml/min.…”

“…34 In other studies, evaluations of estimated glomerular filtration rate (eGFR) mostly showed improvements upon switching from TDF to TAF. 41,46,47,51 Not all TDF to TAF switching studies reported bone-related safety outcomes; however, those that did generally reported improvements (Table 2). 36,[39][40][41][42][43]47 In a prospective, single-arm study, BMD significantly increased from baseline to Week 24 in 75 patients switched from TDF to TAF.…”