Feb 18 2015
By Shreeya Nanda, Senior medwireNews Reporter
Researchers from the Republic of Korea have found that the efficacy of tenofovir disoproxil fumarate (TDF) monotherapy is comparable to that of TDF plus entecavir in chronic hepatitis B (CHB) patients with genotypic resistance to entecavir.
The primary endpoint of virological response, defined as serum levels of hepatitis B virus (HBV) DNA of less than 15 IU/mL at week 48, was achieved by 71.1% of 45 CHB patients harbouring at least one entecavir-resistance mutation who were randomly assigned to receive open-label TDF alone. This did not differ significantly from the 73.3% response rate in the 45 patients treated with TDF plus entecavir.
The researchers point out, however, that the increase in the proportion of patients exhibiting a response was “blunted” from week 24 to 48, raising concerns regarding the effect of prolonging therapy on the rate of virological response.
A similar proportion of patients given TDF and those given TDF plus entecavir achieved HBV DNA levels of less than 60 IU/mL at week 48. And the decrease in mean serum HBV DNA levels during the course of treatment was similar in both study arms.
Moreover, biochemical and serological responses – specifically, the rates of alanine aminotransferase (ALT) normalisation, hepatitis B e antigen seroclearance and hepatitis B s antigen decrease – were also comparable between participants in the TDF monotherapy and dual therapy groups.
Eight patients in the TDF monotherapy group and five in the TDF plus entecavir group had HBV DNA levels above 60 IU/mL at 48 weeks and were thus eligible for genotypic resistance analysis. Six and three participants, respectively, retained their baseline HBV resistance mutations, but no study participant acquired any additional mutations.
The treatment arms were also similar with respect to the occurrence of adverse and serious adverse events.
One patient in the TDF monotherapy group experienced a virological breakthrough, but the team led by Young-Suk Lim (University of Ulsan College of Medicine, Seoul) and Kwan Soo Byun (Korea University College of Medicine, Seoul) attributes this to poor adherence to medication.
Average changes in the estimated glomerular filtration rate and serum phosphate levels were minimal and comparable between groups, report the authors.
Four participants, two in each treatment arm, experienced an ALT flare, defined as a rise in ALT levels of greater than five times the upper limit of normal, but this was transient and did not correlate with an increase in HBV DNA levels.
The team concludes in Gut: “Considering a comparable antiviral efficacy, extremely low risk of TDF resistance, and lower cost, TDF monotherapy would be a reasonable option for the treatment of [entecavir]-resistant patients.”
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