Korean J Gastroenterol.  2021 Jan;77(1):22-29. 10.4166/kjg.2020.144.

Maintaining Antiviral Efficacy after Switching to Generic Entecavir 1 mg for Antiviral-resistant Chronic Hepatitis B

Affiliations
  • 1Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea

Abstract

Background/Aims
Clinical equivalence of generic antiviral agents for chronic hepatitis B (CHB) has not been demonstrated, particularly in cases with previous antiviral resistance. Entecavir 1 mg is prescribed frequently as a mono- or combination therapy in antiviral-resistant CHB patients. This study evaluated the efficacy and safety of switching to generic entecavir 1 mg (Baracle ® ) in CHB patients taking brand-name entecavir 1 mg (Baraclude ® ) alone or in combination with other nucleotide analogs after the development of antiviral resistance.
Methods
This study was a single-arm prospective study. The primary endpoint was undetectable HBV DNA (<20 IU/mL) at 12 months after switching treatment. The biochemical and serologic responses, virologic breakthrough, and antiviral resistance rates were also evaluated.
Results
Forty CHB patients with undetectable HBV DNA through the brand-name entecavir 1 mg treatment as a mono- or combination therapy after developing antiviral resistance to nucleos(t)ide analogs were enrolled in this study. No significant difference in the HBV DNA non-detection rate was observed between the baseline and 12 months after switching therapy (p=0.324).Furthermore, non-inferiority of the generic entecavir 1 mg to the brand-name entecavir 1 mg with 10% margin in maintaining undetectable HBV DNA was demonstrated (95% CI -2.80 to 8.20%). Similarly, no difference in the biochemical response rate was observed after switching therapy. Serum hepatitis B e antigen loss was observed in 12.5%. No virologic breakthrough was reported.
Conclusions
Generic entecavir 1 mg is a reasonable alternative to the brand-name entecavir 1 mg in antiviral-resistant CHB patients with viral suppression.

Keyword

Entecavir; Hepatitis B; chronic; Therapeutics

Figure

  • Fig. 1 Study flow chart. HBV, hepatitis B virus; HCC, hepatocellular carcinoma.

  • Fig. 2 Changes in the HBV DNA levels and virologic response rates after the 12 months follow-up according to the treatment group. (A) Changes in the HBV DNA levels after switching to generic entecavir 1 mg. (B) Virologic response rates after 12 months of switching to generic entecavir 1 mg. HBV, hepatitis B virus.

  • Fig. 3 Comparison of the virologic response rate defined by undetectable HBV DNA at baseline and 12 months after switching therapy. Patients received the standard drug (Baraclude® 1 mg; BMS) until the baseline and were switched to and continued the test drug (Baracle® 1 mg; Dong-A ST) for 12 months. HBV, hepatitis B virus; BMS, Bristol-Myers Squibb; ST, Science Technology; PP, per protocol.


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