- Category: Approved HBV Drugs
- Published on Wednesday, 10 October 2012 00:00
- Written by Liz Highleyman
Treating chronic hepatitis B with entecavir (Baraclude) alone worked as well as dual therapy using entecavir plus tenofovir (Viread) for patients starting treatment for the first time, according to a study described in the September 2012 issue of Gastroenterology.
Several nucleoside/nucleotide analogs are active against hepatitis B virus (HBV), but the virus can develop resistance to these drugs -- especially when they are used alone -- which may compromise long-term treatment success. Resistance develops rapidly with lamivudine (3TC; Epivir), the old standard of care, but some newer drugs have a higher barrier to resistance.
Anna Lok from the University of Michigan Health System and fellow investigators with the international BE-LOW study (ETV-110) compared the safety and efficacy of entecavir monotherapy versus a combination of entecavir plus tenofovir for chronic hepatitis B.
This open-label multicenter study included 379 patients not previously treated with nucleoside/nucleotide analogs. About 70% were men and the average age was 40 years; approximately half were white and half Asian. About 70% were hepatitis B "e" antigen (HBeAg) positive, the rest HBeAg negative. At baseline the average HBV viral load was 7.5 log IU/mL.
Participants were randomly assigned to receive 0.5 mg once-daily entecavir either alone or in combination with 300 mg once-daily tenofovir for 100 weeks. The primary endpoint was the proportion of patients with undetectable HBV DNA (< 50 IU/mL) at week 96.
- Overall, at 96 weeks, comparable proportions of patients in the entecavir monotherapy and entecavir/tenofovir arms achieved undetectable HBV viral load (83.2% vs 76.4%, respectively).
- Among HBeAg positive patients, more participants in the entecavir/tenofovir arm achieved undetectable HBV DNA (80.4% vs 69.8%, respectively), a difference that barely reached statistical significance (P = 0.046).
- However, further analysis showed that this difference was apparent only in HBeAg positive patients with high baseline HBV DNA >100 million IU/mL (79% vs 62%, respectively), not in those with lower viral load (83% in both arms).
- Among HBeAg negative patients, virological response rates were also similar, about 90% in both arms.
- Rates of HBeAg loss and HBeAg seroconversion were comparable in the 2 treatment groups
- Alanine aminotransferase (ALT) normalization, however, occurred more often in the entecavir monotherapy arm (82% vs 69%, respectively).
- No entecavir or tenofovir drug resistance mutations were detected in either arm.
- Rates of adverse events and serious adverse events were comparable in the 2 arms, although fewer people discontinued treatment with entecavir monotherapy compared with combination therapy (1% vs 3%, respectively).
- A small and similar proportion of patients in both arms (2%-3%) experienced elevated serum creatinine, a possible indicator of kidney toxicity, which has been linked to tenofovir.
"The antiviral efficacy of entecavir monotherapy is comparable to that of entecavir plus tenofovir in a mixed population of [nucleoside/nucleotide]-naive patients with chronic hepatitis B," the study authors concluded. "The combination therapy could provide an incremental benefit to HBeAg-positive patients with baseline levels of HBV DNA > 108 IU/mL."
AS Lok, H Trinh, G Carosi, et al. Efficacyof Entecavir With or Without Tenofovir Disoproxil Fumarate for Nucleos(t)ide-Naive Patients With Chronic Hepatitis B. Gastroenterology 143(3):619-628.e1. September 2012.