A Dose-Ranging Study of the Efficacy and Tolerability of Entecavir in Lamivudine-Refractory Chronic Hepatitis B Patients

Università degli Studi di Bari Aldo Moro, Bari, Apulia, Italy
Gastroenterology (Impact Factor: 16.72). 11/2005; 129(4):1198-209. DOI: 10.1053/j.gastro.2005.06.055
Source: PubMed


Entecavir is a nucleoside analogue with potent in vitro activity against lamivudine-resistant hepatitis B virus (HBV). This randomized, dose-ranging, phase 2 study compared the efficacy and safety of entecavir with lamivudine in lamivudine-refractory patients.
Hepatitis B e antigen (HBeAg)-positive and -negative patients (n = 182), viremic despite lamivudine treatment for > or =24 weeks or having documented lamivudine resistance substitutions, were switched directly to entecavir (1.0, 0.5, or 0.1 mg daily) or continued on lamivudine (100 mg daily) for up to 76 weeks.
At week 24, significantly more patients receiving entecavir 1.0 mg (79%) or 0.5 mg (51%) had undetectable HBV DNA levels by branched chain DNA assay compared with lamivudine (13%; P < .0001). Entecavir 1.0 mg was superior to entecavir 0.5 mg for this end point (P < .01). After 48 weeks, mean reductions in HBV DNA levels were 5.06, 4.46, and 2.85 log(10) copies/mL on entecavir 1.0, 0.5, and 0.1 mg, respectively, significantly higher than 1.37 log(10) copies/mL on lamivudine. Significantly higher proportions of patients achieved normalization of alanine aminotransferase levels on entecavir 1.0, 0.5, and 0.1 mg (68%, 59%, and 47%, respectively) than on lamivudine (6%). One virologic rebound due to resistance occurred (in the 0.5-mg group).
In HBeAg-positive and HBeAg-negative lamivudine-refractory patients, treatment with entecavir 1.0 and 0.5 mg daily was well tolerated and resulted in significant reductions in HBV DNA levels and normalization of alanine aminotransferase levels. One milligram of entecavir was more effective than 0.5 mg in this population.

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    • "Our search of clinical databases identified 3,000 abstracts; 179 articles, including clinical study reports (CSRs), were ordered/requested for review, of which 35 (six CSRs) met the inclusion criteria [13-48]. The contents of five of the CSRs had been reported in peer reviewed publications already captured by the search and hence the published data were used [18,26,37,42,44]. One CSR (BMS study AI463023) [13] and the Summary of Product Characteristics for telbivudine [22] were included in the review. "
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    ABSTRACT: To date no network meta-analysis (NMA) has accounted for baseline variations in viral load when assessing the relative efficacy of interventions for chronic hepatitis B (CHB). We undertook baseline-adjusted and unadjusted analyses using the same data to explore the impact of baseline viral load (BVL) on CHB treatment response. We searched Embase, Medline, Medline in Process and the Cochrane CENTRAL databases for randomised clinical trials (RCTs) of monotherapy interventions at licensed doses for use in CHB. Search strategies comprised CHB disease and drug terms (a combination of controlled vocabulary and free text terms) and also a bespoke RCT filter.The NMA was undertaken in WinBUGs using fixed and random effects methods, using data obtained from a systematic review. Individual patient data (IPD) from an entecavir clinical trial were used to quantify the impact of different baseline characteristics (in particular undetectable viral load (UVL) at 1 year) on relative treatment effect. Study level mean baseline values from all identified studies were used. Results were generated for UVL and presented as relative risks (RRs) and 95% credible intervals (CrIs) using entecavir as reference treatment. Overall, for all eight relevant interventions we identified 3,000 abstracts. Following full text review a total of 35 (including the contents of six clinical study reports) met the inclusion critera; 19 were in hepatitis B e antigen (HBeAg)-positive patients and 14 of the 19 contained outcome information of relevance to the NMA.Entecavir and tenofovir studies had heterogeneous patient populations in terms of BVL (mean values 9.29 and 8.65 log10 copies/ml respectively). After adjusting UVL for BVL using an informative prior based on the IPD analysis, the difference between entecavir and tenofovir was not statistically significant (RR 1.27, 95% CrI 0.96 to 1.47 - fixed effects). A similar conclusion was found in all sensitivity analyses. Adjusted tenofovir results were more consistent with observed clinical trial response rates. This study demonstrates the importance of adjusting for BVL when assessing the relative efficacy of CHB interventions in achieving UVL. This has implications for both clinical and economic decision making.
    Full-text · Article · Mar 2014 · Systematic Reviews
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    • "Entecavir (Baraclude®; Bristol-Myers Squibb, New York, NY, USA) is a deoxyguanosine analogue for the treatment of chronic hepatitis B viral infection in adults. With a 50% effective concentration, it has more than 300 times greater potency than lamivudine in vitro, which was the first oral anti-hepatitis B virus (HBV) nucleoside analog found to be effective for treating chronic hepatitis B when administered for the short1,2. The current phase II dose-ranging trial evaluated the good tolerability of 0.1 mg and 0.5 mg entecavir daily for 52 weeks in nucleoside-naive chronic hepatitis B patients3. "
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    ABSTRACT: Entecavir (Baraclude®, Bristol-Myers Squibb) is a potent and selective antiviral agent that has demonstrated efficacy in patients with chronic hepatitis B. The most frequent adverse events attributed to entecavir include increased alanine aminotransferase, upper respiratory tract infection, headache, abdominal pain, cough, pyrexia, fatigue, and diarrhea. Although quite a few randomized double-blind studies including ones investigating adverse events along with these general symptoms have been reported, few cases of cutaneous adverse events have been described in detail. We demonstrate a case of granulomatous drug eruption as a cutaneous adverse event induced by entecavir.
    Full-text · Article · Nov 2013 · Annals of Dermatology
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    • "Entecavir is more effective than adefovir dipivoxil, with a favorable safety profile and low incidence of resistance [18]. We switched adefovir dipivoxil with entecavir hydrate as previously reported [19,20]. Entecavir may be a good treatment choice. "
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