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

J 2017

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

FUNG, Scott, Peter KWAN, Milotka FABRI, Andrzej HORBAN, Mijomir PELEMIS et. al.

Basic information

Original name

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

Authors

FUNG, Scott (124 Canada), Peter KWAN (124 Canada), Milotka FABRI (688 Serbia), Andrzej HORBAN (616 Poland), Mijomir PELEMIS (688 Serbia), Hie-Won HANN (840 United States of America), Selim GUREL (792 Turkey), Florin A. CARUNTU (642 Romania), John F. FLAHERTY (840 United States of America), Benedetta MASSETTO (840 United States of America), Kyungpil KIM (840 United States of America), Kathryn M. KITRINOS (840 United States of America), G. Mani SUBRAMANIAN (840 United States of America), John G. MCHUTCHISON (840 United States of America), Leland J. YEE (840 United States of America), Magdy ELKHASHAB (124 Canada), Thomas BERG (276 Germany), Ioan SPOREA (642 Romania), Cihan YURDAYDIN (792 Turkey), Petr HUSA (203 Czech Republic, guarantor, belonging to the institution), Maciej S. JABLKOWSKI (616 Poland) and Edward GANE (554 New Zealand)

Edition

Journal of Hepatology, Amsterdam, Elsevier Science BV, 2017, 0168-8278

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30219 Gastroenterology and hepatology

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 15.040

RIV identification code

RIV/00216224:14110/17:00095992

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.jhep.2016.08.008

UT WoS

000390642900003

Keywords in English

Bone mineral density; Emtricitabine; Lamivudine resistant; Renal function; Tenofovir disoproxil fumarate; Viral suppression

Abstract

V originále

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 300 mg or FTC 200 mg and TDF 300 mg once daily in a prospective, double blind, study. The proportion of patients with plasma hepatitis B virus (HBV) DNA <69 IU/m1 (<400 copies/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 240 weeks 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 <69 IU/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 (similar to 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 240 weeks. 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 240 weeks.

Citovat

FUNG, Scott, 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 and Edward GANE. Tenofovir disoproxil fumarate (TDF) vs. emtricitabine (FTC)/TDF in lamivudine resistant hepatitis B: A 5-year randomised study. Journal of Hepatology. Amsterdam: Elsevier Science BV, 2017, vol. 66, No 1, p. 11-18. ISSN 0168-8278. Available from: https://dx.doi.org/10.1016/j.jhep.2016.08.008.

@article{1366478,
   author = {Fung, Scott and Kwan, Peter and Fabri, Milotka and Horban, Andrzej and Pelemis, Mijomir and Hann, HieandWon and Gurel, Selim and Caruntu, Florin A. and Flaherty, John F. and Massetto, Benedetta and Kim, Kyungpil and Kitrinos, Kathryn M. and Subramanian, G. Mani and McHutchison, John G. and Yee, Leland J. and Elkhashab, Magdy and Berg, Thomas and Sporea, Ioan and Yurdaydin, Cihan and Husa, Petr and Jablkowski, Maciej S. and Gane, Edward},
   article_location = {Amsterdam},
   article_number = {1},
   doi = {http://dx.doi.org/10.1016/j.jhep.2016.08.008},
   keywords = {Bone mineral density; Emtricitabine; Lamivudine resistant; Renal function; Tenofovir disoproxil fumarate; Viral suppression},
   language = {eng},
   issn = {0168-8278},
   journal = {Journal of Hepatology},
   title = {Tenofovir disoproxil fumarate (TDF) vs. emtricitabine (FTC)/TDF in lamivudine resistant hepatitis B: A 5-year randomised study},
   volume = {66},
   year = {2017}
}

TY  - JOUR
ID  - 1366478
AU  - Fung, Scott - Kwan, Peter - Fabri, Milotka - Horban, Andrzej - Pelemis, Mijomir - Hann, Hie-Won - Gurel, Selim - Caruntu, Florin A. - Flaherty, John F. - Massetto, Benedetta - Kim, Kyungpil - Kitrinos, Kathryn M. - Subramanian, G. Mani - McHutchison, John G. - Yee, Leland J. - Elkhashab, Magdy - Berg, Thomas - Sporea, Ioan - Yurdaydin, Cihan - Husa, Petr - Jablkowski, Maciej S. - Gane, Edward
PY  - 2017
TI  - Tenofovir disoproxil fumarate (TDF) vs. emtricitabine (FTC)/TDF in lamivudine resistant hepatitis B: A 5-year randomised study
JF  - Journal of Hepatology
VL  - 66
IS  - 1
SP  - 11-18
EP  - 11-18
PB  - Elsevier Science BV
SN  - 01688278
KW  - Bone mineral density
KW  - Emtricitabine
KW  - Lamivudine resistant
KW  - Renal function
KW  - Tenofovir disoproxil fumarate
KW  - Viral suppression
N2  - 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 300 mg or FTC 200 mg and TDF 300 mg once daily in a prospective, double blind, study. The proportion of patients with plasma hepatitis B virus (HBV) DNA <69 IU/m1 (<400 copies/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 240 weeks 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 <69 IU/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 (similar to 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 240 weeks. 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 240 weeks.
ER  -

FUNG, Scott, 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 and Edward GANE. Tenofovir disoproxil fumarate (TDF) vs. emtricitabine (FTC)/TDF in lamivudine resistant hepatitis B: A 5-year randomised study. \textit{Journal of Hepatology}. Amsterdam: Elsevier Science BV, 2017, vol.~66, No~1, p.~11-18. ISSN~0168-8278. Available from: https://dx.doi.org/10.1016/j.jhep.2016.08.008.

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