THE COMPARISON OF THERAPEUTIC RESPONSE BETWEEN CLEVUDINE AND ENTECAVIR IN THE TREATMENT-NAIVE PATIENTS WITH CHRONIC HBV INFECTION: FOLLOW-UP DATA UP TO 24 MONTHS

Abstract

Background/Aims: Several nucleoside analogues including lamivudine, entecavir, and clevudine are currently used for the primary treatment of chronic hepatitis B in Korea. Although, both clevudine and entecavir are highly potent antiviral agents, no data is available comparing the clinical efficacy. The aims of this study are to compare virologic, biochemical, and serologic response rates of clevudine and entecavir as well as treatment failure rates.

Methods: Medical records of the patients who started clevudine (n=77) or entecavir (n=149) as a primary treatment of chronic hepatitis B at Korea University Ansan or Guro Hospital between January 2007 and December 2008 were retrospectively reviewed. Patients with hepatocellular carcinoma, concomitant HCV, HDV or HIV infection were excluded. Patients were followed up at 3 months interval. We compared virologic response (HBV DNA<300 copies/mL), biochemical response (ALT<45 IU/L), HBeAg seroconversion and resistance rates up to 24 months. In addition, adverse events during the treatment were assessed.

Results: Baseline characteristics of the patients such as age, sex, proportion of patients with liver cirrhosis, HBeAg positivity, and mean levels of HBV DNA, ALT, and bilirubin were not significantly different between the groups (p>0.05). Virologic responses at 6, 12, 18, 24 months were 57.3% (43/75), 67.1% (51/76), 68.8%(44/64), 76.9% (30/39) in clevudine group, and 55.2%(80/145), 78.9% (116/147), 84.4% (119/141), 85.1%(86/101) in entecavir group, (p=0.760, 0.054, 0.010,0.247) respectively. Virologic responses were significantly different at 18 months, but not at 24 months on per protocol basis(including patients completed treatment at each time point). However, when analyzed on intention to treat basis for virologic response at 24 months, the response rates were 45.3% in clevudine group and 69.8% in entecavir group, which are significantly different (p=0.002). Rates of biochemical response and HBeAg seroconversion were not significantly different between the groups at all time points. Up to 24 months, antiviral resistant mutation (rtM204I) developed only in clevudine group (18/77, 23.4%). Adverse events were monitored, and clevudine had to be discontinued due to muscle related problems such as muscle weakness with elevation of CPK or myopathy, in 8 out of 77 (10.4%) cases at median time of 71.3 weeks.

Conclusions: Although both drug showed potent antiviral activity, virologic responses were better in entecavir group compared with those in clevudine group since 18 months. Long-term treatment with clevudine needs careful monitoring for the development of drug resistance and muscle related problems.