Entecavir plus tenofovir combination therapy for chronic hepatitis B in patients with previous nucleos(t)ide treatment failure.

Abstract

BACKGROUND AND AIMS:

In patients with chronic hepatitis B (CHB) who have failed on other nucleos(t)ide analogs (NUCs), the combination of entecavir (ETV) plus tenofovir disoproxil fumarate (TDF), two potent agents with non-overlapping resistance profiles, may provide a single rescue regimen.

METHODS:

In this single-arm, open-label study, 92 CHB patients with a primary non-response, partial response, or virologic breakthrough on their current NUC were switched to ETV (1 mg) plus TDF (300 mg) and treated for 96 weeks.

RESULTS:

At baseline, 62 % of patients were HBeAg(+) and mean HBV DNA was 4.4 log10IU/mL. Patients had received ≥1 line of prior NUC therapy, with the latest regimen consisting of monotherapy with ETV (53 %), lamivudine (LVD 22 %), TDF (12 %), adefovir (ADV 4 %), or telbivudine (2 %), or combinations of these agents (7 %); 58 % had evidence of single- or multidrug resistance mutations (LVD 52 %, ETV 26 %; ADV 7 %). Response rates for HBV DNA <50 IU/mL were 76 % (70/92) at week 48 (primary endpoint), and 85 % (78/92) at week 96, including 80 % (16/20) in prior LVD failures, 100 % (4/4) in ADV failures, 82 % (9/11) in TDF failures, and 88 % (42/48) in ETV failures. No treatment-emergent resistance to ETV or ADV was observed. ETV/TDF was well tolerated, with no significant renal or additive toxicities observed.

CONCLUSIONS:

In NUC-experienced patients who have failed prior NUC therapy, ETV/TDF was well tolerated and effective, achieving virologic suppression through 96 weeks in the majority (85 %), irrespective of prior NUC exposure, without occurrence of treatment-emergent resistance to either agent.

• Authors: Fabien Zoulim, Jolanta Białkowska-Warzecha, Mircea Mihai Diculescu, Adrian Eugen Goldis, Renate Heyne, Tomasz Mach, Patrick Marcellin, Jörg Petersen, Krzysztof Simon, Soumaya Bendahmane, Isabelle Klauck, Wojciech Wasiak, Harry L A Janssen
• Journal: Hepatology international (Hepatol Int) Vol. 10 Issue 5 Pg. 779-88 (Sep 2016) ISSN: 1936-0541 [Electronic] United States
• PMID: 27206517 (Publication Type: Clinical Trial, Journal Article, Multicenter Study)

Chemical References

• Antiviral Agents
• DNA, Viral
• Hepatitis B e Antigens
• entecavir
• Guanine
• Tenofovir

Topics

• Adult
• Antiviral Agents (administration & dosage)
• DNA, Viral (blood)
• Drug Administration Schedule
• Drug Resistance, Viral
• Drug Therapy, Combination
• Female
• Guanine (administration & dosage, analogs & derivatives)
• Hepatitis B e Antigens (blood)
• Hepatitis B virus (drug effects, genetics, immunology)
• Hepatitis B, Chronic (blood, drug therapy, virology)
• Humans
• Male
• Middle Aged
• Tenofovir (administration & dosage)
• Treatment Outcome
• Viral Load