Relapse of hepatitis B in HBeAg-negative chronic hepatitis B patients who discontinued successful entecavir treatment: The case for continuous antiviral therapy☆
Received 1 April 2008; received in revised form 20 August 2008; accepted 24 October 2008. published online 19 November 2008.
Background/Aims
To evaluate the off-treatment durability of response in HBeAg-negative chronic hepatitis B patients who achieved a protocol-defined ‘Response’ (HBV-DNA<0.7MEq/mL and ALT<1.25×ULN) with entecavir at 48 weeks and the efficacy of entecavir in patients treated beyond one year.
Methods
Entecavir-treated and lamivudine-treated patients who achieved a protocol-defined ‘Response’ were evaluated off-treatment for HBV-DNA<300copies/mL and ALT normalisation. Entecavir- and lamivudine-treated patients who achieved a protocol-defined ‘Virological Response’ (HBV-DNA<0.7MEq/mL but ALT⩾1.25×ULN) at 48 weeks, continued blinded treatment until they achieved Response or 96 weeks, whichever came first.
Results
Among ‘Responders’ who discontinued treatment after 48 weeks, 7/257 (3%) entecavir-treated and 10/201 (5%) lamivudine-treated patients sustained HBV-DNA below 300copies/mL at 24-weeks off-treatment. Among the 54 patients who continued blinded treatment in the second year, 7/26 (27%) entecavir-treated and 6/28 (21%) lamivudine-treated patients normalised ALT and 22/26 (85%) entecavir-treated and 16/28 (57%) lamivudine-treated patients maintained HBV-DNA<300copies/mL at end-of-dosing. The safety profiles of both drugs remained comparable through a second year of treatment.
Conclusions
The majority of protocol-defined Responders relapsed after 1 year when treatment was discontinued. Treatment with entecavir beyond 1 year provided continued virological and biochemical benefit.
☆ (www.clinicaltrials.gov identifier: NCT00035789). Grant Support: The study was sponsored by Bristol-Myers Squibb. The sponsor designed the study in collaboration with a panel of expert hepatologists. The sponsor also collected the data, monitored study conduct, performed the statistical analyses, and coordinated writing of the manuscript with all authors. Employees of Bristol-Myers Squibb: Ricardo Tamez: employee of Bristol-Myers Squibb, Research & Development, Princeton, NJ, USA, Joanna Yang: employee of Bristol-Myers Squibb, Research & Development, Wallingford, CT, USA, Daniel Tenney: employee of Bristol-Myers Squibb, Research & Development, Wallingford, CT, USA, Helena Brett-Smith: employee of Bristol-Myers Squibb, Research & Development, Wallingford, CT, USA. Financial Disclosure Information: Daniel Shouval: BMS: grant support, Ching-Lung Lai: Investigator: BMS, LG Lifesciences; Advisory Board: BMS, Idenix Pharmaceuticals, GSK; Speaker Bureau: BMS; Unrestricted grant: BMS, Ting-Tsung Chang: Nothing to disclose, Hugo Cheinquer: BMS consultant, Paul Martin: BMS: consultant, speaker, investigator, Giampiero Carosi: Nothing to disclose, Steven Han: BMS: consultant, speakers bureau and research grant, Sabahattin Kaymakoglu. Nothing to disclose.
ABSTRACT