PMID- 29151700
OWN - NLM
STAT- MEDLINE
DCOM- 20180717
LR  - 20181113
IS  - 2219-2840 (Electronic)
IS  - 1007-9327 (Print)
IS  - 1007-9327 (Linking)
VI  - 23
IP  - 41
DP  - 2017 Nov 7
TI  - Tenofovir vs lamivudine plus adefovir in chronic hepatitis B: TENOSIMP-B study.
PG  - 7459-7469
LID - 10.3748/wjg.v23.i41.7459 [doi]
AB  - AIM: To demonstrate the non-inferiority (15% non-inferiority limit) of 
      monotherapy with tenofovir disoproxil fumarate (TDF) vs the combination of 
      lamivudine (LAM) plus adefovir dipivoxil (ADV) in the maintenance of virologic 
      response in patients with chronic hepatitis B (CHB) and prior failure with LAM. 
      METHODS: This study was a Phase IV prospective, randomized, open, controlled 
      study with 2 parallel groups (TDF and LAM+ADV) of adult patients with hepatitis B 
      e antigen (HBeAg)-negative CHB, prior failure with LAM, on treatment with LAM+ADV 
      for at least 6 mo, without prior resistance to ADV and with an undetectable viral 
      load at the start of the study, in 14 Spanish hospitals. The follow-up time for 
      each patient was 48 wk after randomization, with quarterly visits in which the 
      viral load, biochemical and serological parameters, adverse effects, adherence to 
      treatment and consumption of hospital resources were analysed. RESULTS: Forty-six 
      patients were evaluated [median age: 55.4 years (30.2-75.2); 84.8% male], 
      including 22 patients with TDF and 24 with LAM+ADV. During study development, 
      hepatitis B virus DNA (HBV-DNA) remained undetectable, all patients remained 
      HBeAg negative, and hepatitis B surface antigen (HBsAg) positive. Alanine 
      aminotransferase (ALT) values at the end of the study were similar in the 2 
      groups (25.1 +/- 7.65, TDF vs 24.22 +/- 8.38, LAM+ADV, P = 0.646). No significant 
      changes were observed in creatinine or serum phosphorus values in either group. 
      No significant differences between the 2 groups were noted in the identification 
      of adverse effects (AEs) (53.8%, TDF vs 37.5%, LAM+ADV, P = 0.170), and none of 
      the AEs which occurred were serious. Treatment adherence was 95.5% and 83.3% in 
      the TDF and the LAM+ADV groups, respectively (P = 0.488). The costs associated 
      with hospital resource consumption were significantly lower with the TDF 
      treatment than the LAM+ADV treatment (euro4943 +/- 1059 vs euro5811 +/- 1538, respectively, 
      P < 0.001). CONCLUSION: TDF monotherapy proved to be safe and not inferior to the 
      LAM+ADV combination therapy in maintaining virologic response in patients with 
      CHB and previous LAM failure. In addition, the use of TDF generated a significant 
      savings in hospital costs.
FAU - Rodriguez, Manuel
AU  - Rodriguez M
AD  - Division of Gastroenterology and Hepatology. Hospital Universitario Central de 
      Asturias, Oviedo 33011, Spain. amunoz@porib.com.
FAU - Pascasio, Juan Manuel
AU  - Pascasio JM
AD  - Unit for the Clinical Management of Digestive Diseases, IBIS, Hospital 
      Universitario Virgen del Rocio, Sevilla 41013, Spain and CIBERehd.
FAU - Fraga, Enrique
AU  - Fraga E
AD  - Liver Transplantation and Hepatology Unit, Gastroenterology Service, Hospital 
      Universitario Reina Sofia, Cordoba 14004, Spain.
FAU - Fuentes, Javier
AU  - Fuentes J
AD  - Digestive Medicine Service, Hospital Universitario Miguel Servet, Zaragoza 50009, 
      Spain.
FAU - Prieto, Martin
AU  - Prieto M
AD  - Hepatology Unit, Digestive Medicine Service, Hospital Universitari i Politecnic 
      La Fe, Valencia 46026, Spain and CIBERehd.
FAU - Sanchez-Antolin, Gloria
AU  - Sanchez-Antolin G
AD  - Hepatology Unit, Hospital Universitario Rio Hortega, Valladolid 47012, Spain.
FAU - Calleja, Jose Luis
AU  - Calleja JL
AD  - Liver Unit, Hospital Universitario Puerta de Hierro de Majadahonda, Universidad 
      Autonoma de Madrid, Madrid 28049, Spain.
FAU - Molina, Esther
AU  - Molina E
AD  - Digestive Medicine Service, Hospital Clinico de Santiago de Compostela, La Coruna 
      15706, Spain.
FAU - Garcia-Buey, Maria Luisa
AU  - Garcia-Buey ML
AD  - Liver Unit, Hospital Universitario de La Princesa, Madrid 28006, Spain and 
      CIBERehd.
FAU - Blanco, Maria Angeles
AU  - Blanco MA
AD  - Digestive Medicine Service, Hospital General Universitario Gregorio Maranon, 
      Madrid 28007, Espana.
FAU - Salmeron, Javier
AU  - Salmeron J
AD  - Digestive Medicine Unit, Complejo Hospitalario de Granada, Granada 18014, Spain.
FAU - Bonet, Maria Lucia
AU  - Bonet ML
AD  - Digestive Medicine Service, Hospital Universitario Son Espases, Palma de Mallorca 
      07120, Spain.
FAU - Pons, Jose Antonio
AU  - Pons JA
AD  - Hepatology Unit, IMIB Hospital Universitario Virgen de la Arrixaca, Murcia 30120, 
      Spain.
FAU - Gonzalez, Jose Manuel
AU  - Gonzalez JM
AD  - Digestive Medicine Service, Hospital Clinico Universitario de Valladolid, 
      Valladolid 47003, Spain.
FAU - Casado, Miguel Angel
AU  - Casado MA
AD  - Pharmacoeconomics and Outcomes Research Iberia, Madrid 28224, Spain.
FAU - Jorquera, Francisco
AU  - Jorquera F
AD  - Division of Gastroenterology and Hepatology, Complejo Asistencial Universitario 
      de Leon, Leon 24001, Spain CIBERehd and IBIOMED Leon.
CN  - TENOSIMP-B Research Group
LA  - eng
PT  - Clinical Trial, Phase IV
PT  - Comparative Study
PT  - Equivalence Trial
PT  - Journal Article
PL  - United States
TA  - World J Gastroenterol
JT  - World journal of gastroenterology
JID - 100883448
RN  - 0 (Antiviral Agents)
RN  - 0 (DNA, Viral)
RN  - 0 (Hepatitis B Surface Antigens)
RN  - 0 (Hepatitis B e Antigens)
RN  - 0 (Organophosphonates)
RN  - 2T8Q726O95 (Lamivudine)
RN  - 99YXE507IL (Tenofovir)
RN  - EC 2.6.1.2 (Alanine Transaminase)
RN  - JAC85A2161 (Adenine)
RN  - U6Q8Z01514 (adefovir dipivoxil)
SB  - IM
MH  - Adenine/*analogs & derivatives/economics/pharmacology/therapeutic use
MH  - Adult
MH  - Aged
MH  - Alanine Transaminase/blood
MH  - Antiviral Agents/economics/pharmacology/*therapeutic use
MH  - DNA, Viral/isolation & purification
MH  - Drug Resistance, Viral
MH  - Drug Therapy, Combination/adverse effects/economics/methods
MH  - Female
MH  - Hepatitis B Surface Antigens/immunology
MH  - Hepatitis B e Antigens/immunology
MH  - Hepatitis B virus/drug effects/physiology
MH  - Hepatitis B, Chronic/blood/*drug therapy/immunology
MH  - Hospital Costs/statistics & numerical data
MH  - Humans
MH  - Lamivudine/economics/pharmacology/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Organophosphonates/economics/pharmacology/*therapeutic use
MH  - Prospective Studies
MH  - Tenofovir/economics/pharmacology/*therapeutic use
MH  - Treatment Failure
MH  - Viral Load/drug effects
PMC - PMC5685852
OTO - NOTNLM
OT  - Adherence
OT  - Costs
OT  - Efficacy
OT  - Hepatitis B
OT  - Lamivudine+Adefovir
OT  - Safety
OT  - Tenofovir
COIS- Conflict-of-interest statement: Manuel Rodriguez consults for and is on the 
      speaker's bureau for Gilead and AbbVie. Juan Manuel Pascasio consults for and 
      expert advice for BMS, Gilead, AbbVie, MSD and Janssen. Enrique Fraga consults 
      for and is on the speaker's bureau for Gilead, MSD, BMS and AbbVie. Martin Prieto 
      participates in advisory board for AbbVie, Bristol-Myers, Gilead, Janssen and MSD 
      and in lectures for Bristol-Myers, Gilead, Janssen, Janssen and MSD. Jose Luis 
      Calleja consults for and is on the speaker's bureau for: BMS and Gilead. Maria 
      Luisa Garcia-Buey consults for and is on the speakers s bureau for AbbVie, 
      Janssen, and Gilead. The remaining authors declare that they have no conflicts of 
      interest.
EDAT- 2017/11/21 06:00
MHDA- 2018/07/18 06:00
PMCR- 2017/11/07
CRDT- 2017/11/21 06:00
PHST- 2017/03/25 00:00 [received]
PHST- 2017/05/22 00:00 [revised]
PHST- 2017/06/18 00:00 [accepted]
PHST- 2017/11/21 06:00 [entrez]
PHST- 2017/11/21 06:00 [pubmed]
PHST- 2018/07/18 06:00 [medline]
PHST- 2017/11/07 00:00 [pmc-release]
AID - 10.3748/wjg.v23.i41.7459 [doi]
PST - ppublish
SO  - World J Gastroenterol. 2017 Nov 7;23(41):7459-7469. doi: 
      10.3748/wjg.v23.i41.7459.