Clevudine is highly efficacious in hepatitis B e antigen-negative chronic hepatitis B with durable off-therapy viral suppression

Hallym University, Sŏul, Seoul, South Korea
Hepatology (Impact Factor: 11.06). 11/2007; 46(4):1041-8. DOI: 10.1002/hep.21800
Source: PubMed


Clevudine is a pyrimidine analog with potent and sustained antiviral activity against HBV. In the present study, we evaluated the safety and efficacy of clevudine 30 mg daily for 24 weeks and assessed the durability of antiviral response for 24 weeks after cessation of dosing in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (e-CHB). We randomized a total of 86 patients (3:1) to receive clevudine 30 mg (n = 63) or placebo (n = 23) daily for 24 weeks. We followed patients for an additional 24 weeks after withdrawal of treatment. The median changes in HBV DNA from baseline were -4.25 and -0.48 log(10) copies/mL at week 24 in the clevudine and placebo groups, respectively (P < 0.0001). Viral suppression in the clevudine group was sustained after withdrawal of therapy, with 3.11 log(10) reduction at week 48. At week 24 and week 48, 92.1% and 16.4% of patients in the clevudine group had undetectable serum HBV DNA levels by Amplicor PCR assay (<300 copies/mL). The proportion of patients who achieved ALT normalization was 74.6% and 33.3% in the clevudine and placebo groups at week 24, respectively (P = 0.0006). ALT normalization in the clevudine group was well-maintained during the post-treatment follow-up period. The incidence of adverse events was similar in the 2 groups. No resistance to clevudine was detected during treatment. CONCLUSION: A 24-week clevudine therapy was well-tolerated and showed potent and sustained antiviral effect without evidence of viral resistance in e-CHB patients. However, treatment for longer than 24 weeks would be needed to achieve durable remission.

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    • "Clevudine (1-[2-deoxy-2-fluoro-β-arabinofuranosyl] thymine) (CLV) is a pyrimidine analog with potent antiviral activity against hepatitis B virus (HBV).1 CLV inhibits DNA-dependent DNA reverse transcription and priming by HBV polymerase.2 Phase III clinical trial results showed that 24 weeks of CLV therapy had a potent and sustained antiviral effect without clinical evidence of viral resistance during the treatment period in both HBeAg-positive and HBeAg-negative chronic hepatitis B (CHB) patients.3,4 The ability to maintain antiviral activity in a significant portion of patients following the discontinuation of therapy is a unique characteristic of CLV. "
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    ABSTRACT: Clevudine (CLV) has potent antiviral activity against chronic hepatitis B (CHB) virus infection. The long-term efficacy and safety of CLV therapy in naïve patients with CHB were investigated. In this retrospective study, 152 naïve Korean patients with CHB who received 30 mg of CLV once daily for at least 12 months were investigated. The cumulative rates at months 12, 24, and 36, respectively, were 65.8%, 74.7%, and 74.7% for undetectable serum hepatitis B virus (HBV) DNA (<12 IU/mL); 77.6%, 86.2%, and 86.2% for normalization of serum alanine aminotransferase (<40 IU/L); 17.6%, 23.5%, and 23.5% for hepatitis B e antigen (HBeAg) loss or seroconversion; and 6.6%, 22.5%, and 30.0% for viral breakthrough. HBeAg positivity (p=0.010), baseline serum HBV DNA level ≥6 log(10) IU/mL (p=0.032) and detectable serum HBV DNA (≥12 IU/mL) at week 24 (p=0.023) were independently associated with the development of viral breakthrough. During follow-up, CLV-induced myopathy developed in 5.9% of patients. The results of long-term CLV therapy for the treatment of naïve patients with CHB showed a high frequency of antiviral resistance and substantial associated myopathy. Therefore, we advise that CLV should not be used as a first-line treatment for naïve patients given the availability of other more potent, safer antiviral agents.
    Full-text · Article · Oct 2012 · Gut and liver
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    • "In HBeAg-negative patients, 92.1% in the clevudine group had undetectable serum HBV DNA levels at week 24. The proportion of patients who achieved ALT normalization was 74.6% and 33.3% in clevudine and placebo groups at week 24, respectively.63 "
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    ABSTRACT: Although the prevalence of chronic hepatitis B has decreased considerably in recent years due to widespread use of the hepatitis B virus (HBV) vaccine, its prevalence still remains high in adults, and this can place a significant burden on health care in areas with endemic HBV. Since the introduction of nucleos(t)ide analogues (NUCs), there has been marked improvement in the care of patients with chronic hepatitis B, resulting in increased survival. However, the emergence of drug resistance in patients treated with NUCs is a major concern. The number of multi-drug resistant patients is increasing, and many patients may not respond to the currently available drugs. In this review, we describe the current status of NUC therapy for antiviral-naïve and -resistant patients.
    Full-text · Article · Sep 2011 · Gut and liver
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    • "With a limit of detection of < 300 copies/mL, the viral response rate was 76.2% (HBeAg-positive patients, 72.3%; HBeAg-negative patients, 84.2%) at 48 weeks. This result was remarkable enough to be compared with entecavir and tenofovir, which have negative seroconversion rates of 67% and 76%, respectively, after a 1-year treatment, but a direct comparison is difficult because of differences in the study methods and patient characteristics [9,10]. "
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    ABSTRACT: Clevudine, a pyrimidine nucleoside analogue, has potent antiviral effects in patients with chronic viral hepatitis B (CHB). We report the efficacy of initial treatment with clevudine in naïve patients with CHB living in Daejeon and Chungcheong Province, South Korea. One hundred five adults with CHB were administered 30 mg of clevudine per day for an average of 51 weeks. We evaluated viral markers and liver biochemistry retrospectively every 3 months. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and hepatitis B virus (HBV) DNA before the treatment were 184 ± 188 IU/L, 150 ± 138 IU/L, and 7.1 ± 1.2 log copies/mL, respectively. Undetectable rates (< 60 IU/mL) of DNA were 36.2%, 68.9%, 83.6%, 76.2%, and 75.8% at 12, 24, 36, 48, and 60 weeks, respectively. Seroconversion rates were 9.1%, 13.6%, 24.6%, 26.5%, and 26.1% and ALT normalization rates were 64.5%, 78.1%, 87.9%, 90.0% at 12, 24, 36, and 48 weeks, respectively. Six patients (5.7%) had a viral breakthrough. Clevudine is a useful drug in the initial treatment of patients with CHB, with a potent antiviral effect and low incidence of viral breakthrough.
    Full-text · Article · Dec 2010 · The Korean Journal of Internal Medicine
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