Monotherapy with tenofovir disoproxil fumarate for multiple drug-resistant chronic hepatitis B: 3-year trial. | SNFGE.org - Société savante médicale française d'hépato-gastroentérologie et d’oncologie digestive
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Thématique :
- Foie (hors cancers)
Originalité :
Intermédiaire
Solidité :
Très solide
Doit faire évoluer notre pratique :
Dans certains cas
 
 
Nom du veilleur :
Professeur Christine SILVAIN
Coup de coeur :
 
 
Hepatology
  2017/09  
 
  2017 Sep;66(3):772-783.  
  doi: 10.1002/hep.29187  
 
  Monotherapy with tenofovir disoproxil fumarate for multiple drug-resistant chronic hepatitis B: 3-year trial.  
 
  Lim YS, Lee YS, Gwak GY, Byun KS, Kim YJ, Choi J, An J, Lee HC, Yoo BC, Kwon SY  
  https://www.ncbi.nlm.nih.gov/pubmed/28370419  
 
 

Abstract

Combination therapy has been recommended for the treatment of patients harboring multiple drug-resistant hepatitis B virus (HBV). However, we recently demonstrated that monotherapy with tenofovir disoproxil fumarate (TDF) for 48 weeks displayed noninferior efficacy to TDF plus entecavir (ETV) combination therapy in patients with HBV resistant to multiple drugs, including ETV and adefovir. Nonetheless, whether prolonged TDF monotherapy would be safe and increase the virologic response rate in these patients was unclear. Among 192 patients with HBV-resistance mutations to ETV and/or adefovir, who were randomized to receive TDF monotherapy (n = 95) or TDF/ETV combination therapy (n = 97) for 48 weeks, 189 agreed to continue TDF monotherapy (TDF-TDF group) or to switch to TDF monotherapy (TDF/ETV-TDF group) and 180 (93.8%) completed the 144-week study. Serum HBV DNA <15 IU/mL at week 48, the primary efficacy endpoint, was achieved in 66.3% in the TDF-TDF group and 68.0% in the TDF/ETV-TDF group (P = 0.80). At week 144, the proportion with HBV DNA <15 IU/mL increased to 74.5%, which was significantly higher compared with that at week 48 (P = 0.03), without a significant difference between groups (P = 0.46). By on-treatment analysis, a total of 79.4% had HBV DNA <15 IU/mL at week 144. Transient virologic breakthrough occurred in 6 patients, which was due to poor drug adherence. At week 144, 19 patients who had HBV DNA levels >60 IU/mL qualified for genotypic resistance analysis, and 6 retained some of their baseline resistance mutations of HBV. No patients developed additional resistance mutations throughout the study period.

CONCLUSION:

TDF monotherapy was efficacious and safe for up to 144 weeks, providing an increasing rate of virologic response in heavily pretreated patients with multidrug-resistant HBV. (Hepatology 2017;66:772-783).

 

 
Question posée
 
Sûreté et efficacité virologique du ténofovir en monothérapie prolongée (144 semaines) chez des patients infectés par des VHB multirésistants à l’entécavir et/ou adéfovir.
 
Question posée
 
Le ténofovir en monothérapie est efficace en termes d’AND VHB < 15 IU/ml chez 79,4% des patients avec ou non une bithérapie ténofovir/entécavir dans les 48 premières semaines sans développer de résistances supplémentaires.
 
Commentaires

Efficacité du ténofovir même chez les patients ayant un VHB très résistant. L’impact rénal est surtout noté chez les patients antérieurement traités par adéfovir. 

 
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