PMID- 26704693
OWN - NLM
STAT- MEDLINE
DCOM- 20160802
LR  - 20220316
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Linking)
VI  - 63
IP  - 4
DP  - 2016 Apr
TI  - Safety and efficacy of ledipasvir/sofosbuvir for the treatment of genotype 1 
      hepatitis C in subjects aged 65 years or older.
PG  - 1112-9
LID - 10.1002/hep.28425 [doi]
AB  - Elderly subjects have been historically underrepresented in clinical trials 
      involving antiviral hepatitis C therapies. The aim of this analysis was to 
      retrospectively evaluate the safety and efficacy of ledipasvir/sofosbuvir 
      (LDV/SOF) by age groups of <65 years versus >/=65 years among subjects enrolled in 
      phase 3 trials. Four open-label phase 3 clinical trials evaluated the safety and 
      efficacy of LDV/SOF with or without ribavirin (RBV) for the treatment of genotype 
      1 chronic hepatitis C virus. Sustained virological response at 12 weeks, 
      treatment-emergent adverse events (AEs), and graded laboratory abnormalities were 
      analyzed according to age group. Of the 2293 subjects enrolled in four phase 3 
      trials, 264 (12%) were >/=65 years of age, of whom 24 were aged >/=75 years. 
      Sustained virological response at 12 weeks was achieved by 97% (1965/2029) of 
      subjects aged <65 years and 98% (258/264) of subjects aged >/=65 years. The most 
      common AEs in both LDV/SOF groups that occurred in >/=10% of subjects were headache 
      and fatigue. The rate of study discontinuation due to AEs was similar in the two 
      age cohorts. The use of RBV in 1042 (45%) subjects increased the number of AEs, 
      treatment-related AEs, and AEs leading to study drug modification/interruption, 
      particularly among elderly subjects. CONCLUSIONS: LDV/SOF with or without RBV was 
      highly effective for treatment of genotype 1 chronic hepatitis C virusin subjects 
      aged 65 and older. Addition of RBV did not increase sustained virological 
      response at 12 weeks rates but led to higher rates of AEs, especially in elderly 
      subjects.
CI  - (c) 2015 by the American Association for the Study of Liver Diseases.
FAU - Saab, Sammy
AU  - Saab S
AD  - University of California Los Angeles, Los Angeles, CA.
FAU - Park, Sarah H
AU  - Park SH
AD  - University of California Los Angeles, Los Angeles, CA.
FAU - Mizokami, Masashi
AU  - Mizokami M
AD  - National Center for Global Health and Medicine, Tokyo, Japan.
FAU - Omata, Masao
AU  - Omata M
AD  - Yamanashi Prefectural Hospital Organization, Yamanashi, Japan.
FAU - Mangia, Alessandra
AU  - Mangia A
AD  - Liver Unit, Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy.
FAU - Eggleton, Ed
AU  - Eggleton E
AD  - Gilead Sciences, Foster City, CA.
FAU - Zhu, Yanni
AU  - Zhu Y
AD  - Gilead Sciences, Foster City, CA.
FAU - Knox, Steven J
AU  - Knox SJ
AD  - Gilead Sciences, Foster City, CA.
FAU - Pang, Phil
AU  - Pang P
AD  - Gilead Sciences, Foster City, CA.
FAU - Subramanian, Mani
AU  - Subramanian M
AD  - Gilead Sciences, Foster City, CA.
FAU - Kowdley, Kris
AU  - Kowdley K
AD  - Swedish Medical Center, Seattle, WA.
FAU - Afdhal, Nezam H
AU  - Afdhal NH
AD  - Beth Israel Deaconess Medical Center, Boston, MA.
LA  - eng
PT  - Comparative Study
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160222
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Antiviral Agents)
RN  - 0 (Benzimidazoles)
RN  - 0 (Fluorenes)
RN  - 013TE6E4WV (ledipasvir)
RN  - 49717AWG6K (Ribavirin)
RN  - WJ6CA3ZU8B (Sofosbuvir)
SB  - IM
MH  - Age Factors
MH  - Aged
MH  - Aged, 80 and over
MH  - Antiviral Agents/administration & dosage
MH  - Benzimidazoles/*administration & dosage
MH  - Clinical Trials, Phase III as Topic
MH  - Cohort Studies
MH  - Confidence Intervals
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Drug Therapy, Combination
MH  - Female
MH  - Fluorenes/*administration & dosage
MH  - Follow-Up Studies
MH  - Genotype
MH  - Hepatitis C, Chronic/diagnosis/*drug therapy/genetics
MH  - Humans
MH  - Liver Cirrhosis/prevention & control/virology
MH  - Male
MH  - Patient Safety/statistics & numerical data
MH  - Randomized Controlled Trials as Topic
MH  - Retrospective Studies
MH  - Ribavirin/*administration & dosage
MH  - Risk Assessment
MH  - Sex Factors
MH  - Sofosbuvir/*administration & dosage
MH  - Treatment Outcome
EDAT- 2015/12/26 06:00
MHDA- 2016/08/03 06:00
CRDT- 2015/12/26 06:00
PHST- 2015/11/05 00:00 [received]
PHST- 2015/12/17 00:00 [revised]
PHST- 2015/12/21 00:00 [accepted]
PHST- 2015/12/26 06:00 [entrez]
PHST- 2015/12/26 06:00 [pubmed]
PHST- 2016/08/03 06:00 [medline]
AID - 10.1002/hep.28425 [doi]
PST - ppublish
SO  - Hepatology. 2016 Apr;63(4):1112-9. doi: 10.1002/hep.28425. Epub 2016 Feb 22.