Eficácia do adefovir dipivoxil, entecavir e telbivudina para o tratamento da hepatite crônica B: revisão sistemática

BackgroundAntiviral treatment with nucleoside analogs has been used for chronic hepatitis B (CHB). Each kind of nucleoside analog has its own characteristics and suitability for patients. Telbivudine (LdT, brand name: Sebivo, Beijing Novartis Pharma Ltd) is the newest nucleoside analog, with strong and rapid viral suppression. However, its resistance rate is relatively high during long-term application, due to low genetic barriers to resistance. So, it is necessary to increase the effect and reduce resistance with effective management, according to baseline factors and early on-treatment responses.ObjectivesTo reveal possible predictive factors of the effect of telbivudine (LdT) treatment on naïve HBeAg-positive chronic hepatitis B (CHB) patients to optimize treatment.Patients and MethodsA total 71 naïve chronic hepatitis B (CHB) patients who met the inclusion criteria were enrolled. All patients were treated with LdT 600 mg Qd for at least 52 weeks. Multiple logistic regression analyses were done to investigate the predictive values of baseline factors and responses at Week 24.ResultsThe reduction in hepatitis virus B (HBV) DNA level was 6.44 ± 2.38 lg copies/mL at Week 52 compared with baseline. The complete virus response (CVR), biochemical response (BR), serological response (SR), and drug resistance (DR) were 61.99%, 77.46%, 35.21%, and 8.45% respectively. By multiple regression analysis, baseline alanine aminotransferase (ALT) levels significantly affected CVR (P = 0.024, OR = 1.008), and baseline ALT and baseline HBV DNA levels were independent compact factors of SR (P = 0.012, OR = 1.007; P = 0.001, OR = 0.423). The differences in CVR, SR, and DR in patients with ALT > 120 Iu/mL compared with patients with ALT ≤ 120 Iu/mL were statistically significant. The differences in SR in patients with HBV DNA > 107 copies/mL compared with patients with HBV DNA ≤ 107 copies/mL were statistically significant. Additionally, CVR, BR, and SR were differed significantly between patients with HBV DNA lower than 300 copies/mL at Week 24 and patients with HBV DNA higher than 300 copies/mL (P = 0.000, P = 0.0016, and P = 0.000, respectively).ConclusionsThere were more responders among naïve HBeAg-positive chronic hepatitis B patients with lower HBV DNA levels (especially lower than 107 copies/mL) and higher ALT values (especially higher than 120 Iu/mL at baseline) to LdT treatment. Adjustments for treatment strategy should be considered if HBV DNA > 300 copies/mL at Week 24 is observed.

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“…Another type was the rtLl80M + rtM204V alliance mutation. These results are consistent with other published data [7][8]. …”

Section: Discussionsupporting

confidence: 94%

Effect and Predictive Elements for 52 Weeks’ Telbivudine Treatment on Naïve HBeAg positive Chronic Hepatitis B

et al. 2011

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“…According to the findings of the present study and those from previous studies, telbivudine is more suitable for CHB patients with a high HBeAg level, owing to its high rates of HBeAg disappearance and HBeAg seroconversion. Entecavir is more suitable for CHB patients with active HBV DNA duplication and resistance (40), owing to its low incidence of adverse events. There are several limitations in the present study.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Telbivudine Compared to Entecavir Among HBeAg+ Chronic Hepatitis B Patients: a Meta-Analysis Study

et al. 2013

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BackgroundHepatitis B virus (HBV) infection is a serious global health problem that is associated with huge social and economic costs. Early antiviral drugs, such as interferon-α2b, peginterferon-α2a, lamivudine, and adefovir, all have their limitations (such as low responses or safety concerns) in clinical application. Telbivudine and entecavir are two of the latest nucleotide drugs and both have been shown to have potent viral suppression. However, in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB), inconsistent results have been generated for efficacy between telbivudine and entecavir. Therefore, evidence-based medical data are required to compare the efficacies, in terms of virological and biochemical responses, and safety between telbivudine and entecavir.ObjectivesWe aimed to compare the early antiviral efficacy and safety of telbivudine and entecavir in the treatment of patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB).Patients and MethodsA search for relevant randomized controlled trials (RCTs) on HBeAg-positive CHB patients treated with telbivudine and entecavir for 24 or 52 weeks, published before December 2011, was performed. Primary efficacy endpoint was the cumulative rate of undetectable HBV DNA, and secondary efficacy endpoints included rates of alanine aminotransferase (ALT) normalization, HBeAg disappearance, HBeAg seroconversion and adverse events. Meta-analysis was performed using the Review Manager v5.1.4 software package. We assessed the pooled risk ratios (RRs) and 95% confidence intervals (CIs) using the fixed-or random-effects model.ResultsSix randomized controlled trials (RCTs) involving 555 patients were included. Telbivudine was associated with significantly higher rates of HBeAg disappearance (RR = 1.46, 95% CI: 1.11 - 1.91) and HBeAg seroconversion (RR = 1.76, 95%CI: 1.25-2.48) than entecavir, but had higher adverse events (RR = 2.11, 95%CI: 1.23 - 3.60), compared with entecavir. There was no difference between telbivudine and entecavir in the rate of cumulative undetectable HBV DNA (RR = 0.99, 95% CI: 0.90 - 1.10) and ALT normalization (RR = 0.93, 95% CI: 0.85 - 1.00).ConclusionsTelbivudine is associated with significantly higher rates of HBeAg disappearance and HBeAg seroconversion than entecavir, whereas entecavir is superior to telbivudine in safety. Both drugs have similar efficacy on rates of cumulative undetectable HBV DNA and ALT normalization.

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“…A systematic revision of studies on the effectiveness of these drugs has shown the occurrence of at least one adverse event; however, this was not considered in the modelling. 1 Moreover, tenofovir, the drug currently recommended by the Ministério da Saúde 3 as the fi rst option for treating patients who are carriers of CHB without cirrhosis, was not included as it did not have authorization from ANVISA (National Agency of Health Monitoring) to be used in the treatment of hepatitis B.…”

Section: Discussionmentioning

confidence: 99%

“…Currently, drugs such as adefovir, entecavir and tenofovir are also included. b A systematic review 1 showed adefovir, entecavir and telbivudina effectiveness to be similar to or greater than lamivudine's. entecavir may be prescribed as an alternative to lamivudine in treating fi rst time patients with positive and negative HbeAg, due to the low potential for resistance.…”

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confidence: 99%

“…telbivudina is one of the most recent antivirals to be available to treat CHB, it is more powerful than lamivudine in inhibiting viral replication, however, its use leads to strong antiviral resistance. 1 Treatment of CHB aims at reducing the progression of the disease, increasing survival and improving the patients' quality of life. This study aimed at analysing the cost-effectiveness of the alternative drugs with rescue therapy in relapses due to viral resistance.…”

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confidence: 99%

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Custo-efetividade dos análogos de nucleosídeos/nucleotídeos para hepatite crônica B

et al. 2012

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OBJECTIVE:To conduct a cost-effectiveness analysis of drug alternatives with rescue therapy in case of relapse due to viral resistance for the treatment of patients with chronic hepatitis B (CHB). METHODS:Hypothetical cohort of patients with CHB, HBeAg-negative, without clinical or histological evidence of cirrhosis, detectable HBV DNA, histological diagnosis of the disease, positive serum HBsAg for longer than six months, high levels of alanine aminotransferase (ALT) (twice as high as the upper limit of normality) and mean age of 40 years. A Markov model was developed for chronic hepatitis B (HBeAg-negative) with a 40-year time horizon. Costs and benefi ts were discounted at 5%. Annual rates of disease progression, costs due to complications and the effi cacy of medicines were obtained from the literature. One-way and probabilistic sensitivity analysis evaluated uncertainties. RESULTS:Initiation of treatments with entecavir resulted in an increase of 0.35 discounted life-years gained compared to lamivudine. The incremental cost-effectiveness ratio was R$ 16,416.08 per life-years gained. In the sensitivity analysis, the incremental cost-effectiveness ratio was more sensitive to variation in the probability of transition from chronic hepatitis B to compensated cirrhosis, discount rate and medicine prices (± 10%). In the probabilistic sensitivity analysis, the acceptability curve showed that beginning treatment with entecavir was the most cost-effective alternative in comparison with the use of lamivudine. CONCLUSIONS:The availability of entecavir is economically attractive as part of early treatment for patients with chronic hepatitis B without HIV co-infection. Cost-effectiveness: chronic hepatitis B Almeida AM et al Chronic hepatitis B (CHB) is a serious public health problem which affects between 350 and 400 million people worldwide. 2 A population based prevalence study of hepatitis B infection in Brazil revealed endemic levels > 1% across all the capital cities of each region and of the Federal District. The overall prevalence of HbsAg in the Brazilian state capitals was 0.37% (95%CI 0.25;0.50). The prevalence of this marker was 0.055% (95%CI 0.012;0.10) in the ten to 19 year old age group and of 0.6% (95%CI 0.41;0.78) for the 20 to 69 year old age group. The North showed the highest results for both age groups. a Treatment, when prescribed, is critical in avoiding progression and complications of the disease such as compensated cirrhosis, decompensated cirrhosis and hepatocellular carcinoma. a Treatment costs become signifi cantly higher with the high morbidity and mortality of patients in advanced stages of the disease, as serious hepatic complications increase the complexity of treatment and the risk of death. 23 In Brazil, until 2009, the guidelines from advocated interferon and lamivudine for the treatment of CHB. Currently, drugs such as adefovir, entecavir and tenofovir are also included. b A systematic review 1 showed adefovir, entecavir and telbivudina effectiveness to be similar to or grea...

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Eficácia do adefovir dipivoxil, entecavir e telbivudina para o tratamento da hepatite crônica B: revisão sistemática

Cited by 7 publications

References 38 publications

Effect and Predictive Elements for 52 Weeks’ Telbivudine Treatment on Naïve HBeAg positive Chronic Hepatitis B

Effect and Predictive Elements for 52 Weeks’ Telbivudine Treatment on Naïve HBeAg positive Chronic Hepatitis B

Efficacy and Safety of Telbivudine Compared to Entecavir Among HBeAg+ Chronic Hepatitis B Patients: a Meta-Analysis Study

Custo-efetividade dos análogos de nucleosídeos/nucleotídeos para hepatite crônica B

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