Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B

Patrick Marcellin, Ting Tsung Chang, Seng Gee Lim, Myron J. Tong, William Sievert, Mitchell L. Shiffman, Lennox J Jeffers, Zachary Goodman, Michael S. Wulfsohn, Shelly Xiong, John Fry, Carol L. Brosgart

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Abstract

BACKGROUND: In preclinical and phase 2 studies, adefovir dipivoxil demonstrated potent activity against hepatitis B virus (HBV), including lamivudine-resistant strains. METHODS: We randomly assigned 515 patients with chronic hepatitis B who were positive for hepatitis B e antigen (HBeAg) to receive 10 mg of adefovir dipivoxil (172 patients), 30 mg of adefovir dipivoxil (173), or placebo (170) daily for 48 weeks. The primary end point was histologic improvement in the 10-mg group as compared with the placebo group. RESULTS: After 48 weeks of treatment, significantly more patients who received 10 mg or 30 mg of adefovir dipivoxil per day than who received placebo had histologic improvement (53 percent [P<0.001], 59 percent [P<0.001], and 25 percent, respectively), a reduction in serum HBV DNA levels (by a median of 3.52 [P<0.001], 4.76 [P<0.001], and 0.55 log copies per milliliter, respectively), undetectable levels (fewer than 400 copies per milliliter) of serum HBV DNA (21 percent [P<0.001], 39 percent [P<0.001], and 0 percent, respectively), normalization of alanine aminotransferase levels (48 percent [P<0.001], 55 percent [P<0.001], and 16 percent, respectively), and HBeAg seroconversion (12 percent [P=0.049], 14 percent [P=0.01], and 6 percent, respectively). No adefovir-associated resistance mutations were identified in the HBV DNA polymerase gene. The safety profile of the 10-mg dose of adefovir dipivoxil was similar to that of placebo; however, there was a higher frequency of adverse events and renal laboratory abnormalities in the group given 30 mg of adefovir dipivoxil per day. CONCLUSIONS: In patients with HBeAg-positive chronic hepatitis B, 48 weeks of 10 mg or 30 mg of adefovir dipivoxil per day resulted in histologic liver improvement, reduced serum HBV DNA and alanine aminotransferase levels, and increased the rates of HBeAg seroconversion. The 10-mg dose has a favorable risk-benefit profile for long-term treatment. No adefovir-associated resistance mutations were identified in the HBV DNA polymerase gene.

Original languageEnglish
Pages (from-to)808-816
Number of pages9
JournalNew England Journal of Medicine
Volume348
Issue number9
DOIs
StatePublished - Feb 27 2003

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  • Medicine(all)

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Marcellin, P., Chang, T. T., Lim, S. G., Tong, M. J., Sievert, W., Shiffman, M. L., Jeffers, L. J., Goodman, Z., Wulfsohn, M. S., Xiong, S., Fry, J., & Brosgart, C. L. (2003). Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. New England Journal of Medicine, 348(9), 808-816. https://doi.org/10.1056/NEJMoa020681