Efficacy Of Tenofovir Alafenamide Research Articles

Naif Kronik Hepatit B Tedavisinde Tenofovir Alafenamid: Tek Merkezli Retrospektif Çalışma

Kronik hepatit B (KHB), dünya çapında yaklaşık 257 milyon insanı etkileyen önemli bir küresel sağlık sorunudur. Tenofovir alafenamid (TAF), kronik hepatit B tedavisinde kullanılan yeni ve etkili bir antiviral ilaç olmakla birlikte tedaviye naif hastalarda TAF etkinliğine ilişkin gerçek dünya verileri sınırlıdır. Bu çalışmanın amacı, tedaviye naif KHB hastalarında TAF'ın etkinliğini değerlendirmektir. Virolojik yanıt ve alanin aminotransferaz (ALT) normalizasyonu ile ilişkili faktörler de çalışmada analiz edilmiştir. Çalışmaya Ocak 2021-Aralık 2022 tarihleri arasında TAF başlanan 41 tedavi naif KHB hastası dahil edilmiştir. Demografik, klinik ve laboratuvar verileri başlangıçta ve 48. haftada toplanmıştır. Birincil sonlanım noktaları tam virolojik yanıt (TVY) ve 48. haftada ALT normalizasyonu idi. 48. haftada ALT ve hepatit B virüsü-deoksiribonükleik asit (HBV DNA) düzeyleri istatiksel açıdan anlamlı olacak şekilde azalmıştır (her ikisi de p

Real-world safety and effectiveness of tenofovir alafenamide for 144 weeks in Japanese patients with chronic hepatitis B.

Tenofovir alafenamide (TAF), a prodrug of tenofovir, delivers high levels of active drug to hepatocytes and is given in a lower dose than tenofovir disoproxil fumarate (TDF). TAF reduces viral replication in patients with chronic hepatitis B (CHB) similar to TDF and has shown a lower risk of the renal and bone toxicities associated with TDF use. This post-marketing surveillance study examined the safety and effectiveness of TAF in treatment-naïve and -experienced CHB patients who received TAF for 144 weeks at real-world clinical sites in Japan. Safety assessments included the incidence of adverse drug reactions (ADRs), renal and bone events, and changes in selected laboratory parameters. Effectiveness was based on the proportion of patients with HBV DNA levels below the lower limit of quantitation or <29 IU/mL. This analysis included 580 patients; 18.4% of whom were treatment-naïve. The cumulative incidence of ADRs was 0.21 per 100 person-months, and the incidence of serious ADRs was 0.01 (95% CI, 0.00-0.04) per 100 person-months. There were no ADRs of declines in estimated glomerular filtration rates, renal failure or proximal tubulopathy. The most common ADR was hypophosphataemia in seven (1.2%) patients. Two (0.4%) patients each had decreased blood phosphorus, bone mineral density decreased, dizziness and alopecia. Overall, the proportion of virologically suppressed patients increased from 68.8% at baseline to 97.5% at Week 144. These results confirm the real-world safety and effectiveness of TAF in Japanese patients with CHB and are consistent with the findings of other evaluations of the safety and efficacy of TAF in CHB.

Prophylactic tenofovir alafenamide for hepatitis B virus reactivation and reactivation-related hepatitis.

No prospective study on the efficacy of tenofovir alafenamide (TAF), a novel tenofovir prodrug, in preventing HBV reactivation has yet been reported. This multicenter prospective study enrolled HBV-carriers who received TAF to prevent HBV reactivation before antitumor or immunosuppressive therapy, and patients with resolved HBV infection who experienced HBV-reactivation and received TAF to prevent HBV reactivation-related hepatitis. The efficacy of prophylactic TAF in preventing HBV reactivation and HBV reactivation-related hepatitis was evaluated at 6 and 12 months after initiating TAF. Overall, 110 patients were administered TAF to prevent HBV reactivation or HBV reactivation-related hepatitis. Three patients died owing to primary disease, whereas one patient was transferred to another hospital within 6 months after initiating TAF. Seven patients died due to primary disease, and five patients were transferred to another hospital within 12 months after initiating TAF. Therefore, 106 and 94 (77 patients with HBV infection, 17 with previous-HBV infection) patients were evaluated at 6 and 12 months after initiating TAF, respectively. No patient experienced HBV reactivation, HBV reactivation-related hepatitis, or treatment discontinuation due to HBV reactivation or adverse events of TAF after 6 and 12 months. TAF could effectively prevent HBV reactivation and HBV reactivation-related hepatitis. This article is protected by copyright. All rights reserved.

SAT374 - Two-year safety and efficacy of tenofovir alafenamide in chronic hepatitis B: a HEllenic multicenter ReAl-life CLInical Study (HERACLIS-TAF)

SAT374 - Two-year safety and efficacy of tenofovir alafenamide in chronic hepatitis B: a HEllenic multicenter ReAl-life CLInical Study (HERACLIS-TAF)

HERACLIS-TAF: a multi-centre prospective cohort study on 2-year safety and efficacy of tenofovir alafenamide in patients with chronic hepatitis B with renal and/or bone disorders or risks.

Tenofovir alafenamide (TAF) has exhibited a favourable safety profile on estimated glomerular filtration (eGFR) and bone mineral density (BMD), but has not been extensively studied in patients with renal impairment and/or BMD disorders. To assess predictors of eGFR changes and other safety and efficacy outcomes during 24-month TAF therapy in patients with chronic hepatitis B with renal and/or BMD disorders/risks. Adult patients who started TAF at 13 clinics throughout Greece were prospectively included. Main exclusion criteria were hepatitis D, active malignancy and bisphosphonates recent use. MDRD formula was used for eGFR estimation. TAF was initiated in 176 patients (91% switched from another agent). At 12 and 24 months, HBV DNA was undetectable in 97% and 100%, and ALT was normal in 96% and 95% of patients. Median ALT decreased from baseline to month 12/24 (p< 0.001). Mean eGFR decreased from previous treatment initiation to baseline (p< 0.001), increased at 12 months and remained stable at 24 months (p≤ 0.001). An increase in eGFRof >3ml/min at 12 month was observed in 50% of patients and was associated mainly with baseline eGFR 30-60 ml/min. In patients with baseline phosphate <2.5 mg/dl, mean serum phosphate increased at month-12/24 (p< 0.001). Median BMD did not change significantly from baseline to 12 months but improved at 24 months (p= 0.001). In mostly switched patients with renal and/or BMD disorders/risks, eGFR improved after 12-24 months of TAF treatment, especially in patients with baseline eGFR 30-60 ml/min. TAF may also improve low serum phosphate, BMD and ALT, whereas it maintains or induces virological suppression.

Short-term and long-term safety and efficacy of tenofovir alafenamide, tenofovir disoproxil fumarate and entecavir treatment of acute-on-chronic liver failure associated with hepatitis B

Background & AimsThere is limited evidence on the efficacy and safety of nucleos(t) ide analogues (NAs) in the treatment of HBV-ACLF. Our objective was to evaluate the outcomes among TAF, TDF and ETV, three first-line antivirals against chronic hepatitis B, in patients with HBV-ACLF.MethodsPatients with HBV-related ACLF were recruited and received daily TAF (25 mg/d), TDF (300 mg/d) and ETV (0.5 mg/d). They were prospectively followed-up. The primary endpoint was overall survival at week 12 and week 48, the secondary endpoints were virological response and biochemical response.ResultsForty gender and age matched eligible subjects were recruited and divided into three groups: TAF group, TDF group and ETV group. By week 48, 8 (80%) patients in TAF group, 6 (60%) patients in TDF group and 17 (85%) patients in ETV group survived without liver transplantation (P = 0.251). After 4 weeks of NAs treatment, all three groups showed paralleling reduction of HBV DNA levels. All three groups presented similar biochemical responses at week 4, patients treated with TAF showed a priority in total bilirubin reduction, albumin and cholesterol maintenance. Additionally, although there was no significant difference in changes of serum urea, serum creatinine, serum cystatin C and estimated GFR among the three groups by treatment week 4, TDF showed unfavorable renal safety even in short -term treatment. The treatment using NAs was well-tolerated and there was no serious drug-related adverse event reported.ConclusionsTAF, TDF and ETV are of similar efficacy and safety in short-term and long-term treatment of HBV-ACLF.Trial registrationThis study is ongoing and is registered with ClinicalTrials.gov, NCT03640728 (05/02/2019).

The 48-week safety and therapeutic effects of tenofovir alafenamide in hbv-related acute-on-chronic liver failure: A prospective cohort study.

Tenofovir alafenamide (TAF) has been available in China for a short time, little is known about its safety and efficacy in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF). We conducted this study to further verify the safety and efficacy of TAF in these patients. Eighty-eight eligible subjects were included and divided into three groups: TAF group, TDF group and ETV group. Clinical and laboratory test results were collected and the survival status, virus suppression status and liver and renal function improvement were observed during follow-up. No drug-related adverse events were observed within a 48-week observation period. At week 48, the survival rates of the three groups were 56.5%, 78.3% and 59.5% (p=0.262). HBV DNA undetectable rates were similar (80.0% vs.75.0% vs.84.6%, respectively, p=0.863). Liver function improved in all the three groups over time. Compared with the other two groups, patients in the TAF group had a greater decrease in serum creatinine (CR) and an increase in estimated glomerular filtration rate (eGFR), especially at week 12. At week 48, the median changes of CR were -0.7 (IQR -3.0, 13.0) vs. 15.0 (IQR -3.0, 21.0) vs. 5.0 (IQR -9.0, 14.0), respectively (p = 0.334), while the median changes of eGFR were -2.12 (IQR -13.87, 1.44) vs. -10.43 (IQR -20.21, 3.18) vs. -5.31 (IQR -14.72, 5.44) ml/min/1.73m2 , respectively (p = 0.592). In this real-world clinical study, TAF is as effective as TDF and ETV, and may be more beneficial in protecting renal function in the early stages of antiviral therapy.

Safety and efficacy of tenofovir alafenamide in liver transplant recipients: A single center experience.

Tenofovir disoproxil fumarate (TDF) is frequently used for treatment of and prophylaxis against reactivation of hepatitis B virus (HBV) after liver transplant (LT). Because TDF can lead to renal impairment and a decrease in bone mineral density (BMD), the prodrug tenofovir alafenamide (TAF) may be considered a viable alternative with fewer adverse effects. Only limited information is available about the use of TAF for LT recipients. We report a European single-center experience with TAF as treatment for LT patients. This retrospective analysis involved 29 LT recipients receiving standard immunosuppressants (mainly calcineurin inhibitors). Demographic and clinical data were documented at baseline upon switch to TAF and at various time points thereafter. None of the patients experienced HBV reactivation after the switch to TAF. Liver and renal function remained stable. Drug levels of immunosuppressive agents did not change significantly after the switch. After 1year, 22 patients were still taking TAF; two patients had been lost to follow-up; one patient had died; and four patients had discontinued therapy because of TAF-related adverse effects. No serious adverse effects were reported. Tenofovir alafenamide exhibits high antiviral efficacy and a good safety profile for LT recipients. Still, the safety and tolerability of TAF for organ transplant patients should be evaluated in larger cohorts.

SAT461 - Safety and efficacy of tenofovir alafenamide in geriatric patients with chronic hepatitis B: experience from four ongoing phase 2 and phase 3 clinical trials

SAT461 - Safety and efficacy of tenofovir alafenamide in geriatric patients with chronic hepatitis B: experience from four ongoing phase 2 and phase 3 clinical trials

Entecavir treatment of hepatitis B virus-infected patients with severe renal impairment and those on hemodialysis.

Entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) are first-line nucleos(t)ide analogues for hepatitis B virus (HBV)-infected patients. However, consecutive TDF treatment causes renal dysfunction, and the safety and efficacy of TAF have not been established in severe renal dysfunction patients, including hemodialysis patients. The efficacy and safety of ETV in these populations has not been clarified. The study aimed to clarify this. In this retrospective multicenter study, between 2006 and 2018, a total of 567 HBV-infected patients treated with ETV monotherapy were screened. Patients were included if >20years old, treated with ETV monotherapy for >1year, and had proper clinical information. The efficacy of ETV and changes in renal function were evaluated according to renal function. A total of 273 patients were included: 9.2% (25/273), 1.8% (5/273), and 3.7% (10/273) had chronic kidney disease (CKD) stage G3, CKD stage G4/5, and were on hemodialysis, respectively. Overall, 84.2%, 94.0%, and 96.2% of patients experienced serum HBV-DNA disappearance at 1, 2, and 3years, respectively, after treatment initiation. In patients with CKD stage G3-5, estimated glomerular filtration rate tended to restore with time, which was in contrast to patients without renal dysfunction. The rate of disappearance in serum HBV-DNA, alanine transaminase normalization, and virological breakthrough was similar between patients with or without renal dysfunction. ETV showed high efficacy for all 10 hemodialysis patients without virological breakthrough. Entecavir for HBV-infected patients with severe renal dysfunction, including hemodialysis patients, is highly effective and does not affect renal function.

Tenofovir alafenamide plus emtricitabine versus abacavir plus lamivudine for treatment of virologically suppressed HIV-1-infected adults: a randomised, double-blind, active-controlled, non-inferiority phase 3 trial

Abacavir and tenofovir alafenamide offer reduced bone toxicity compared with tenofovir disoproxil fumarate. We aimed to compare safety and efficacy of tenofovir alafenamide plus emtricitabine with that of abacavir plus lamivudine. In this randomised, double-blind, active-controlled, non-inferiority phase 3 trial, HIV-1-positive adults (≥18 years) were screened at 79 sites in 11 countries in North America and Europe. Eligible participants were virologically suppressed (HIV-1 RNA <50 copies per mL) and on a stable three-drug regimen containing abacavir plus lamivudine. Participants were randomly assigned (1:1) by a computer-generated allocation sequence (block size 4) to switch to fixed-dose tablets of tenofovir alafenamide (10 mg or 25 mg) plus emtricitabine (200 mg) or remain on abacavir (600 mg) plus lamivudine (300 mg), with matching placebo, while continuing to take the third drug. Randomisation was stratified by the third drug (boosted protease inhibitor vs other drug) at screening. Investigators, participants, and study staff giving treatment, assessing outcomes, and collecting data were masked to treatment group. The primary endpoint was the proportion of participants with virological suppression (HIV-1 RNA <50 copies per mL) at week 48 (assessed by snapshot algorithm), with a 10% non-inferiority margin. We analysed the primary endpoint in participants enrolled before May 23, 2016 (when target sample size was reached), and we analysed safety in all enrolled participants who received at least one dose of study drug (including patients enrolled after these dates). This study was registered with ClinicalTrials.gov, number NCT02469246. Study enrolment began on June 29, 2015, and the cutoff enrolment date for the week 48 primary endpoint analysis was May 23, 2016. 501 participants were randomly assigned and treated. At week 48, virological suppression was maintained in 227 (90%) of 253 participants receiving tenofovir alafenamide plus emtricitabine compared with 230 (93%) of 248 receiving abacavir plus lamivudine (difference -3·0%, 95% CI -8·2 to 2·0), showing non-inferiority. Few participants discontinued treatment because of adverse events: 12 (4%) of 280 participants in the tenofovir alafenimide plus emtricitabine group and nine (3%) of 276 in the abacavir plus lamivudine group. Three participants had serious, treatment-related adverse events: one each with renal colic and neutropenia in the tenofovir alafenamide plus emtricitabine group, and one myocardial infarction in the abacavir plus lamivudine group. There were no treatment-related deaths. Tenofovir alafenamide, in combination with emtricitabine and various third drugs, maintained high efficacy with a renal and bone safety profile similar to that of abacavir. In virologically suppressed patients, a regimen containing tenofovir alafenamide could be an alternative to those containing abacavir, without concern for new onset of renal or bone toxicities or hyperlipidaemia. Gilead Sciences Inc.

Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBeAg-negative chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial

The novel prodrug tenofovir alafenamide delivers the nucleotide reverse transcriptase inhibitor tenofovir to target cells more efficiently at a lower dose than tenofovir disoproxil fumarate, thereby reducing systemic exposure. We compared the efficacy and safety of the two drugs in patients with HBeAg-negative chronic hepatitis B virus (HBV) infection in a non-inferiority study. In this ongoing randomised, double-blind, phase 3, non-inferiority study in 105 centres in 17 countries, patients with HBeAg-negative chronic HBV were randomly assigned (2:1) by a computer-generated allocation sequence (block size six), stratified by plasma HBV DNA concentration and previous treatment status, to receive once-daily oral doses of tenofovir alafenamide 25 mg or tenofovir disoproxil fumarate 300 mg, each with matching placebo. Participants, investigators, and those assessing outcomes were masked to group assignment. Eligible patients were aged at least 18 years with HBeAg-negative chronic HBV infection (with plasma HBV DNA concentrations of >20 000 IU/mL), serum alanine aminotransferase concentrations of greater than 60 U/L in men or greater than 38 U/L in women and at no more than ten times the upper limit of normal, and estimated creatinine clearance of at least 50 mL/min (by the Cockcroft-Gault method). The primary efficacy endpoint was the proportion of patients who had HBV DNA less than 29 IU/mL at week 48 in those who received at least one dose of study drug; the study was powered to show non-inferiority with a 10% efficacy margin of tenofovir alafenamide compared with tenofovir disoproxil fumarate. Bone and renal safety, and key secondary safety endpoints were assessed sequentially. The study will be conducted for a total of 3 years as a double-blind comparison to assess the longer term response to treatment. This study is registered with ClinicalTrials.gov, number NCT01940341. Between Sept 12, 2013, and Oct 31, 2014, 426 patients were randomly assigned (285 assigned to tenofovir alafenamide and 141 assigned to tenofovir disoproxil fumarate; one patient assigned to tenofovir disoproxil fumarate did not receive the treatment. 268 (94%) of 285 patients receiving tenofovir alafenamide had HBV DNA less than 29 IU/mL at week 48 versus 130 (93%) of 140 patients receiving tenofovir disoproxil fumarate (difference 1·8% [95% CI -3·6 to 7·2]; p=0·47), which demonstrates non-inferiority. Patients receiving tenofovir alafenamide had significantly smaller mean percentage declines in bone mineral density than those receiving tenofovir disoproxil fumarate (hip -0·29% [95% CI -0·55 to -0·03] vs -2·16% [-2·53 to -1·79], adjusted percentage difference 1·87% [95% CI 1·42 to 2·32; p<0·0001]; spine -0·88% [-1·22 to -0·54] vs -2·51% [-3·09 to -1·94], adjusted percentage difference 1·64% [95% CI 1·01 to 2·27]; p<0·0001). At week 48, mean change in serum creatinine was small in both groups (tenofovir alafenamide 0·01 mg/dL [95% CI 0·00 to 0·02] vs tenofovir disoproxil fumarate 0·02 mg/dL [0·00 to 0·04], adjusted percentage difference -0·01 mg/dL [95% CI -0·03 to 0·01]; p=0·32), but patients receiving tenofovir alafenamide had a smaller reduction in creatinine clearance (median change in estimated glomerular filtration rate -1·8 mL/min [IQR -7·8 to 6·0] vs -4·8 mL/min [-12·0 to 3·0]; p=0·004). Most adverse events were mild to moderate in severity in the two treatment groups. The most common adverse events overall were headache (tenofovir alafenamide 40 [14%] patients vs tenofovir disoproxil fumarate 14 [10%] patients), nasopharyngitis (30 [11%] vs 15 [11%]), and upper respiratory tract infection (35 [12%] vs ten [7%]). 14 (5%) patients receiving tenofovir alafenamide and nine (6%) patients receiving tenofovir disoproxil fumarate had serious adverse events, none of which was deemed by investigators to be related to study treatment; one patient in the tenofovir disoproxil fumarate group died, but this was not deemed to be related to study treatment. In patients with HBeAg-negative chronic HBV, the efficacy of tenofovir alafenamide was non-inferior to that of tenofovir disoproxil fumarate, and had improved bone and renal effects. Longer term follow-up is needed to better understand the clinical impact of these changes. Gilead Sciences.