Hepatology research : the official journal of the Japan Society of Hepatology · 2016
Efficacy and safety of tenofovir disoproxil fumarate rescue therapy for chronic hepatitis B patients who failed other nucleos(t)ide analogs.
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Kumada Hiromitsu, Koike Kazuhiko, Suyama Kazuaki, Ito Hiroshi, Itoh Hiroshi, Sugiura Wataru
Аннотация
AIM: Acquisition of nucleos(t)ide analog (NA) inhibitor resistance is critical in successful chronic hepatitis B treatment. As the pattern of tenofovir disoproxil fumarate (TDF) resistance mutations differs from that of other antiviral drugs, we sought to clarify the salvaging potential of TDF in patients with hepatitis B virus (HBV) infection who are poor responders or resistant to other NAs.
METHODS: A prospective, multicenter, single-arm, open-label study was carried out from December 2011 to October 2014. Poor responders defined as subjects with serum HBV-DNA levels >4 log10 copies/mL were enrolled. Subjects receiving lamivudine (LAM) + adefovir pivoxil (ADV) before the initiation of the study were switched to LAM + TDF. Subjects on entecavir hydrate (ETV) with or without ADV were switched to ETV + TDF. The primary efficacy end-point was the proportion of subjects achieving HBV-DNA <2.1 log10 copies/mL (LLQ) at week 24. The secondary efficacy end-points were the proportion of subjects with LLQ at weeks 48 and 96, serum alanine aminotransferase normalization, hepatitis B envelope antigen/antibody and hepatitis B surface antigen/antibody seroconversion.
RESULTS: Thirty-four subjects were enrolled, 21 subjects were switched to ETV + TDF, and 13 subjects were switched to LAM + TDF. Drug resistance mutations were determined in 85% of the subjects at the time of the enrolment. The proportion of subjects who achieved LLQ was 59%, 62%, and 71% at weeks 24, 48, and 96, respectively. No serious adverse event related to TDF was reported.
CONCLUSION: Our study clearly showed that TDF containing regimens were effective in salvaging poor responders and/or those who are drug-resistant to other NAs. This study is registered with ClinicalTrials.gov (NCT01475851) and the GSK Clinical Study Register (GSK LOC115912).
METHODS: A prospective, multicenter, single-arm, open-label study was carried out from December 2011 to October 2014. Poor responders defined as subjects with serum HBV-DNA levels >4 log10 copies/mL were enrolled. Subjects receiving lamivudine (LAM) + adefovir pivoxil (ADV) before the initiation of the study were switched to LAM + TDF. Subjects on entecavir hydrate (ETV) with or without ADV were switched to ETV + TDF. The primary efficacy end-point was the proportion of subjects achieving HBV-DNA <2.1 log10 copies/mL (LLQ) at week 24. The secondary efficacy end-points were the proportion of subjects with LLQ at weeks 48 and 96, serum alanine aminotransferase normalization, hepatitis B envelope antigen/antibody and hepatitis B surface antigen/antibody seroconversion.
RESULTS: Thirty-four subjects were enrolled, 21 subjects were switched to ETV + TDF, and 13 subjects were switched to LAM + TDF. Drug resistance mutations were determined in 85% of the subjects at the time of the enrolment. The proportion of subjects who achieved LLQ was 59%, 62%, and 71% at weeks 24, 48, and 96, respectively. No serious adverse event related to TDF was reported.
CONCLUSION: Our study clearly showed that TDF containing regimens were effective in salvaging poor responders and/or those who are drug-resistant to other NAs. This study is registered with ClinicalTrials.gov (NCT01475851) and the GSK Clinical Study Register (GSK LOC115912).