Tenofovir disoproxil fumarate (TDF) vs. emtricitabine (FTC)/TDF in lamivudine resistant hepatitis B: A 5-year randomised study.

Abstract

BACKGROUND & AIMS:

Long-term treatment with tenofovir disoproxil fumarate (TDF) alone, or in combination with emtricitabine (FTC) is associated with sustained viral suppression in patients with lamivudine resistant (LAM-R) chronic hepatitis B (CHB).

METHODS:

LAM-R CHB patients were randomised 1:1 to receive TDF 300mg or FTC 200mg and TDF 300mg once daily in a prospective, double blind, study. The proportion of patients with plasma hepatitis B virus (HBV) DNA<69IU/ml (<400copies/ml) at week 96 (primary efficacy endpoint) was reported previously. Here we present week 240 follow-up data.

RESULTS:

Overall, 280 patients were randomised to receive TDF (n=141) or FTC/TDF (n=139), and 85.4% completed 240weeks of treatment. At week 240, 83.0% of patients in the TDF arm, and 82.7% of patients in the FTC/TDF treatment arm had HBV DNA<69IU/ml (p=0.96). Rates of normal alanine aminotransferase (ALT) and normalised ALT were similar between groups (p=0.41 and p=0.97 respectively). Hepatitis B e antigen loss and seroconversion at week 240 were similar between groups, (p=0.41 and p=0.67 respectively). Overall, six patients achieved hepatitis B surface antigen (HBsAg) loss and one patient (FTC/TDF arm) had HBsAg seroconversion by week 240. No TDF resistance was observed up to week 240. Treatment was generally well tolerated, and renal events were mild and infrequent (∼8.6%). The mean change in bone mineral density at week 240 was -0.98% and -2.54% at the spine and hip, respectively.

CONCLUSIONS:

TDF monotherapy was effective and well tolerated in LAM-R CHB patients for up to 240weeks.

LAY SUMMARY:

The goal of oral antiviral treatment for chronic hepatitis B (CHB) is to achieve and maintain undetectable HBV DNA levels. Treatment options with enhanced potency, and low risk of resistance development for patients infected with lamivudine resistant (LAM-R) HBV are required. Tenofovir disoproxil fumarate (TDF) monotherapy was effective and well tolerated without TDF resistance development in CHB patients with LAM-R, for up to 240weeks. Clinical trial number: NCT00737568.

• Authors: Scott Fung, Peter Kwan, Milotka Fabri, Andrzej Horban, Mijomir Pelemis, Hie-Won Hann, Selim Gurel, Florin A Caruntu, John F Flaherty, Benedetta Massetto, Kyungpil Kim, Kathryn M Kitrinos, G Mani Subramanian, John G McHutchison, Leland J Yee, Magdy Elkhashab, Thomas Berg, Ioan Sporea, Cihan Yurdaydin, Petr Husa, Maciej S Jablkowski, Edward Gane
• Journal: Journal of hepatology (J Hepatol) Vol. 66 Issue 1 Pg. 11-18 (01 2017) ISSN: 1600-0641 [Electronic] Netherlands
• PMID: 27545497 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Chemical References

• Antiviral Agents
• DNA, Viral
• Hepatitis B Surface Antigens
• Hepatitis B e Antigens
• Tenofovir
• Emtricitabine

Topics

• Adult
• Antiviral Agents (administration & dosage, adverse effects)
• DNA, Viral (blood)
• Double-Blind Method
• Drug Monitoring
• Drug Resistance, Viral
• Drug Therapy, Combination (methods)
• Emtricitabine (administration & dosage, adverse effects)
• Female
• Hepatitis B Surface Antigens (blood)
• Hepatitis B e Antigens (blood)
• Hepatitis B virus (drug effects, isolation & purification, physiology)
• Hepatitis B, Chronic (drug therapy, virology)
• Humans
• Male
• Middle Aged
• Tenofovir (administration & dosage, adverse effects)
• Treatment Outcome
• Viral Load (drug effects)