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EASL 2012: Entecavir plus Tenofovir for Hepatitis B Patients with Prior Treatment Failure

A combination of entecavir (Baraclude) plus tenofovir (Viread) resulted in hepatitis B virus (HBV) suppression in a majority of patients who previously experienced treatment failure, according to a study presented at the 47th Annual Meeting of the European Association for the Study of the Liver (EASL 2012) this week in Barcelona.

Nucleoside/nucleotide analogs are the mainstay of therapy for chronic hepatitis B, but a significant proportion of people do not respond to treatment with a single agent. Combining drugs may result in greater efficacy, especially against resistant virus.

Krzysztof Simon and fellow investigators with the multinational ENTEBE study (AI463203) evaluated the safety and efficacy of a combination regimen containing the nucleoside analog entecavir and the nucleotide analog tenofovir.

This single-arm, open-label study included 80 adult chronic hepatitis B patients in France, Germany, Italy, the Netherlands, Poland, and Romania who did not achieve or maintain viral suppression on a prior course of nucleoside/nucleotide therapy. Treatment failure was defined as < 1 log reduction in HBV DNA after 3 months of treatment (primary non-response), HBV DNA > 50 IU/mL after 24 or 48 weeks of treatment (partial virological response), or  > 1 log increase in viral load over the lowest level (virological breakthrough).

Most participants (76%) were men, 73% were white, and the average age was 44 years. About two-thirds were hepatitis B "e" antigen (HBeAg) positive. Previous failed treatments included lamivudine (3TC; Epivir) monotherapy, adefovir (Hepsera) monotherapy, entecavir monotherapy, telbivudine (Tyzeka) monotherapy, tenofovir monotherapy, lamivudine plus adefovir, lamivudine plus tenofovir, or entecavir plus adefovir. Overall, 12% had prior primary non-response, 56% had prior partial response, and 33% experienced virological breakthrough.

All participants received 1 mg once-daily entecavir plus 300 mg once-daily tenofovir. The primary analysis will be at 48 weeks, with continued follow-up through 96 weeks. Interim 24-week results for 37 patients were presented at EASL.

Results

• 50% of participants achieved HBV DNA < 50 IU/mL at week 12 and 57% did so at week 24.
• The mean viral load change from baseline was -2.5 log IU/mL.
• 1 person achieved HBeAg loss and HBeAg seroconversion.
• None experienced hepatitis B surface antigen (HBsAg) loss or seroconversion.
• Entecavir plus tenofovir was generally well-tolerated.
• Side effects occurring in more than 3% of patients were nausea, diarrhea, fatigue, and hair loss.
• No treatment-related severe adverse events, laboratory abnormalities, or ALT flares were reported.

The findings indicate that entecavir plus tenofovir is an effective and well-tolerated option for chronic hepatitis B patients who did not achieve sustained response with prior treatment.

4/20/12

Reference

K Simon, M Dicelescu, HLA Janssen, et al. The ENTEBE Study: Safety and Efficacy of Entecavir Plus Tenofovir in Adults with Chronic Hepatitis B and Previous Nucleos(t)Ide Treatment Failure. 47th Annual Meeting of the European Association for the Study of the Liver (EASL 2012). Barcelona, April 18-22, 2012. Abstract 542.