493 Phase III comparison of telbivudine vs lamivudine in HBeAg-positive patients with chronic hepatitis B: Efficacy, safety, and predictors of response at 1 year

Gane, E.; Lai, CL; Liaw, Y.E.; Thongsawat, Satawat; Wang, Y.; Cheng, Yu-Shu; Heathcote, Jenny; Rasenacks, J.; Bzowej, Natalie; Naoumov, Nikolai V.; Chao, George; Fielman, B.; Brown, Nathaniel

doi:10.1016/s0168-8278(06)80493-9

Cited by 8 publications

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“…Comparing the efficacy of treatment is difficult; however, some comparative studies have been performed. Both entecavir and telbivudine proved superior efficacy over lamivudine after 1 year of treatment [13,15,63,64] . Direct comparison of telbivudine or adefovir for 52 wk showed superior efficacy on viral and biochemical parameters for telbivudine, but resistance was not assessed [65] .…”

Section: Treatment With Nucleoside/ Nucleotide Analoguesmentioning

confidence: 97%

“…Entecavir showed no resistance up to 2 years of treatment; however, complete non-responders did not receive treatment in year 2 [75] . Telbivudine had a resistance rate of 2%-4% after 1 year of treatment [63,65] . With long-ter m lamivudine treatment HBeAg seroconversion increases to 27%, 40%, 47% and 50% at year 2, 3, 4 and 5, respectively, despite the development of resistance [67,71,73,76] .…”

Section: Treatment With Nucleoside/ Nucleotide Analoguesmentioning

confidence: 99%

“…Presuming study randomisation led to an equal distribution of both viral and host factors, it is to be expected that more potent drugs are able to suppress viral replication in subjects with suboptimal suppression. Entecavir and telbivudine proved their superior potency over lamivudine in a head to head comparison and for telbivudine this observation also has been made in comparison with adefovir [13,15,[63][64][65] . In adefovir treatment failures the more potent drug tenofovir showed good viral suppression [93] .…”

Section: Management Of Treatment Failures To Nucleos(t)ide Analoguesmentioning

confidence: 99%

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Future prospectives for the management of chronic hepatitis B

Leemans

Janssen

Man³

2007

WJG

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Chronic hepatitis B virus infection affects about 400 million people around the globe and causes approximately one million deaths a year. Since the discovery of interferon-α as a therapeutic option the treatment of hepatitis B has evolved fast and management has become increasingly complicated. T h e a m o u n t o f v ira l re p l ic a t io n re f le c t e d in t he viral load (HBV-DNA) plays an important role in the development of cirrhosis and hepatocellular carcinoma. The current treatment modalities for chronic hepatitis B are immunomodulatory (interferons) and antiviral suppressants (nucleoside and nucleotide analogues) all with their own advantages and limitations. An overview of the treatment efficacy for both immunomodulatory as antiviral compounds is provided in order to provide the clinician insight into the factors influencing treatment outcome. With nucleoside or nucleotide analogues suppression of viral replication by 5-7 log10 is feasible, but not all patients respond to therapy. Known factors influencing treatment outcome are viral load, ALT levels and compliance. Many other factors which might influence treatment are scarcely investigated. Identifying the factors associated with response might result in stopping rules, so treatment could be adapted in an early stage to provide adequate treatment and avoid the development of resistance. The efficacy of compounds for the treatment of mutant virus and the crossresistance is largely unknown. However, genotypic and phenotypic testing as well as small clinical trials provided some data on efficacy in this population. Discontinuation of nucleoside or nucleotide analogues frequently results in viral relapse; however, some patients have a sustained response. Data on the risk factors for relapse are necessary in order to determine when treatment can be discontinued safely. In conclusion: chronic hepatitis B has become a treatable disease; however, much research is needed to tailor therapy to an individual patient, to predict the sustainability of response and determine the best treatment for those failing treatment.

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Section: Treatment With Nucleoside/ Nucleotide Analoguesmentioning

confidence: 97%

Section: Treatment With Nucleoside/ Nucleotide Analoguesmentioning

confidence: 99%

Section: Management Of Treatment Failures To Nucleos(t)ide Analoguesmentioning

confidence: 99%

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Future prospectives for the management of chronic hepatitis B

Leemans

Janssen

Man³

2007

WJG

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“…Guidelines for the management of CHB address the criteria for patient selection, the objectives and timing of therapy, and the advantages and disadvantages of available treatment options, but little information is available on treatment monitoring and strategies for optimizing patient outcomes [1][2][3][4][5]. Emerging evidence from clinical studies of antiviral agents suggest that on-treatment serum levels of hepatitis B virus (HBV) DNA are predictive of treatment response [6][7][8][9]. Based on these findings, a panel of international experts has proposed an algorithm for optimizing treatment response that relies on the on-treatment monitoring of HBV DNA levels [10].…”

Section: Introductionmentioning

confidence: 99%

Current approaches for treating chronic hepatitis B: when to start, what to start with, and when to stop

Chang

Suh

2008

Hepatol Int

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The natural course of hepatitis B virus (HBV) infection is variable, and chronic hepatitis B (CHB) disease exhibits itself through a spectrum of clinical manifestations. These factors contribute to the challenges faced when managing patients who live with HBV infection. Furthermore, conventional treatment options (e.g., interferon alfa-2a, lamivudine, and adefovir) are moderately effective and can be associated with problems, such as poor tolerability (interferon alfa-2a) and the development of drug resistance (lamivudine). Over the last 5 years, several antiviral agents including entecavir, peginterferon alfa-2a, and telbivudine which are more efficacious and have improved tolerability over previous drugs have become available. The availability of novel antiviral agents and advances in understanding resistance patterns of antiviral agents has resulted in refinement of CHB treatment recommendations and guidelines. More recently, evidence from clinical trials suggests the central importance of virologic suppression as an indicator of treatment outcome and the predictive value of on-treatment HBV DNA levels in response to antiviral therapy. This review highlights the goals of therapy and clinical experience with therapies that are newly licensed or in the late stages of clinical development. Current approaches for treating CHB and new strategies for optimizing response to therapy are also discussed.

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“…1 In clinical trials, oral products administered up to 1 year to treat this chronic condition have demonstrated similar rates of hepatitis B e antigen (HBeAg) seroconversion from HBeAgpositive to HBeAg-negative status with the detection of hepatitis B e antibody (anti-HBe) ranging from 17% to 27% in adults. [2][3][4][5] Costs, however, can vary widely. Factors affecting costs include the direct cost of the drug, length of treatment, and complications associated with continued therapy (e.g., development of resistance, intolerable adverse events).…”

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confidence: 99%

Cost-Effective Pharmacologic Therapies to Treat Chronic Hepatitis B: How Far Have We Really Come?

Holbrook¹

2008

JMCP

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of lamivudine with entecavir appears impractical. According to American Association for the Study of Liver Disease (AASLD) guidelines, lamivudine is preferred for short (undefined) courses of treatment. 8 In addition, this pharmacoeconomic (PE) model proposed by Yuan et al. begins with a hypothetical population of lamivudine treatment-naïve individuals in the base-case model, and conclusions are drawn from the sensitivity analysis in which more than half of the patient population develops resistance to lamivudine within 10 years. This population is quite different from that of the Benefits of Entecavir for Hepatitis B Liver Disease (BEHoLD) study in which 2% of patients in the entecavir study group and 18% of patients in the lamivudine study group experienced virologic rebound during the first year of therapy. In the BEHoLD study, virologic rebound was used as a determinant to identify if resistance, defined as an increase in HBV DNA by at least 1 log 10 copies per mL from the nadir, occurred during the treatment period.2 The continued use of lamivudine in treating lamivudine-resistant individuals has been associated with a diminished treatment response (i.e., higher pretreatment HBV DNA and ALT levels). 10 The clinical significance of this observation, however, has not been fully elucidated. 11The incidence and clinical course of CHB are different in developing countries than in the United States. In the United States, the risk of adults developing CHB from acute exposure to HBV is < 5% while the incidence of CHB in endemic areas (e.g., Southeast Asia) can range from 25% to 30% in infants and children under the age of 5 years to as high as 90% in newborns of HBeAg-positive mothers. [12][13][14][15][16] Cohorts in studies describing the natural history of CHB can be categorized into 2 basic groups: (1) patients born in areas with high and intermediate prevalence rates for HBV and (2) patients in high-risk groups (e.g., intravenous drug users, homosexual men, inmates of correctional institutions, and individuals coinfected with hepatitis C virus or human immunodeficiency virus). This is an important consideration when evaluating drug therapy. Those who develop CHB early in life (i.e., acquired at birth from an infected mother or during early childhood) from an acute exposure experience disease progression and develop serious liver complications (i.e., compensated and decompensated cirrhosis and hepato cellular carcinoma) by the fourth decade of life due to the prolonged immune tolerance phase that is characterized by persistence of HBeAg, persistence of viremia for a longer duration, and normal ALT/aspartate aminiotransferase (AST) levels. The prolonged immune tolerance phase is followed by a prolonged immune clearance phase (i.e., longer time to S ix products are approved in the United States for the treatment of chronic hepatitis B (CHB) viral infection: interferon alfa-2b, recombinant (Intron-A); peginterferon alfa-2a (Pegasys); lamivudine (Epivir HBV); adefovir dipivoxil (Hepsera); entecavir (Baraclude); and ...

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493 Phase III comparison of telbivudine vs lamivudine in HBeAg-positive patients with chronic hepatitis B: Efficacy, safety, and predictors of response at 1 year

Cited by 8 publications

References 0 publications

Future prospectives for the management of chronic hepatitis B

Future prospectives for the management of chronic hepatitis B

Current approaches for treating chronic hepatitis B: when to start, what to start with, and when to stop

Cost-Effective Pharmacologic Therapies to Treat Chronic Hepatitis B: How Far Have We Really Come?

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