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Tenofovir effective treatment for patients with hepatitis B
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A once-daily dose of tenofovir suppressed hepatitis B virus more effectively than adefovir, according to findings from two phase-3 studies published in The New England Journal of Medicine.
The study’s researchers enrolled patients from May 2005 to June 2006. The two separate studies examined patients with HBV who were hepatitis B e antigen–negative and those who were HBeAg–positive. The researchers then randomly assigned patients in each study to receive either tenofovir (Viread, Gilead) or adefovir (Hepsera, Gilead) in a 2:1 ratio.
All eligible patients received at least one dose of the drugs. In the first study, there were 375 participants in the HBeAg–negative arm, 250 of whom received tenofovir and 125 of whom received adefovir. In the second study, there were 266 patients in the HBeAg–positive arm, 176 of whom received tenofovir and 90 of whom were administered adefovir.
Double-blind treatment lasted 48 weeks. Patients underwent liver biopsies within the six months before screening and at some point between weeks 44 and 48.
The primary endpoint was to reduce HBV DNA levels to less than 400 copies/mL in patients plus histologic improvement, which was defined as a reduction in the Knodell necroinflammation score of two or more points without worsening fibrosis, according to the findings. Other goals included serologic response, normalization of alanine aminotransferase levels and development of resistance mutations.
Robust results
Viral suppression occurred in 93% of HBeAg–negative patients receiving tenofovir and 63% of patients in the same group receiving adefovir. In the HBeAg–positive group, 76% of patients receiving tenofovir reached the viral suppression endpoint compared with 13% of patients receiving adefovir. Tenofovir was also significantly more effective than adefovir in normalizing alanine aminotransferase levels in HBeAg–positive patients: 68% vs. 54%. HBeAg–positive patients in the tenofovir arm were also significantly more likely to experience loss of hepatitis B surface antigen than those being administered adefovir: 3% vs. 0%.
Regarding resistance, the researchers wrote that “amino acid substitutions within HBV DNA polymerase associated with decreased sensitivity to tenofovir or known resistance to other drugs to treat HBV infection had not developed in any of the patients.” Prior lamivudine (Epivir, GlaxoSmithKline) treatment did not influence the efficacy of tenofovir with regard to HBV DNA response.
Both treatments demonstrated similar safety profiles, according to the researchers.
The trial is ongoing, and signs indicated that 96-week results will be consistent with those from week 48. “Patients switching from adefovir to tenofovir at week 48 had dramatic declines in HBV DNA,” researchers said. – by Rob Volansky
For more information:
- Marcellin P, Heathcote J, Buti M, et al. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B. N Engl J Med. 2008;359:2442-2455.