Published on Monday, 11 November 2013
Written by Liz Highleyman
A dual regimen of entecavir (Baraclude) plus tenofovir (Viread) for 48 weeks led to virological response and was generally well-tolerated as second-line therapy for chronic hepatitis B patients who had failed previous nucleoside/nucleotide treatment, according to a poster presentation at the 64th AASLD Liver Meeting last week in Washington, DC.
Chronic hepatitis B virus (HBV) infection is treated with oral nucleoside/nucleotide analogs including entecavir, tenofovir, lamivudine (Epivir), adefovir (Hepsera), and telbivudine (Tyzeka). While these drugs can reduce HBV viral load to an undetectable level while on therapy, they typically do not lead to post-treatment sustained virological response or hepatitis B antigen loss.
HBV can develop resistance mutations that compromise long-term efficacy — especially of the oldest drug, lamivudine — and limit future treatment options, but entecavir and tenofovir have a higher barrier to resistance.
Maciej Jablkowski of the Medical University of Lodz in Poland and colleagues conducted the ENTEBE study (AI463203) to evaluate the safety and efficacy of entecavir plus tenofovir in chronic hepatitis B patients who had failed previous nucleoside/nucleotide therapy.
This multicenter Phase 3b trial enrolled 92 participants. Three-quarters were men, 76% were white, and the median age was 43 years. A majority (62%) were hepatitis B “e” antigen (HBeAg) positive and 76% had normal alanine amino transferase (ALT) at baseline. People with decompensated liver disease were excluded.
Most participants had previously been treated with entecavir (53%) or lamivudine (22%) monotherapy; 12% had taken tenofovir and a few had used adefovir (4%) or telbivudine (2%). About 5% had tried dual combinations that included lamivudine or adefovir.
Patients had experienced prior treatment failure as defined by European Association for the Study of the Liver (EASL) guidelines. Nearly 10% had primary non-response (1 log but still detectable at week 24 or 48) and 33% experienced viral breakthrough while on treatment (>1 log increase over the lowest level). At baseline 52% had evidence of lamivudine resistance, 25% had entecavir resistance, and 7% had adefovir resistance; about one-quarter had no resistance mutations and 16% had viral load too low for sequencing.
All participants in this ongoing, open-label, single-arm study were re-treated with 1 mg entecavir plus 300 mg tenofovir, both once-daily, for up to 96 weeks. After 96 weeks patients and investigators could elect to pursue further treatment using commercially available hepatitis B drugs.