PMID- 25963890
OWN - NLM
STAT- MEDLINE
DCOM- 20150916
LR  - 20201209
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Linking)
VI  - 62
IP  - 1
DP  - 2015 Jul
TI  - Safety and tolerability of ledipasvir/sofosbuvir with and without ribavirin in 
      patients with chronic hepatitis C virus genotype 1 infection: Analysis of phase 
      III ION trials.
PG  - 25-30
LID - 10.1002/hep.27890 [doi]
AB  - In phase III studies, treatment with the once-daily fixed-dose combination tablet 
      of ledipasvir/sofosbuvir (LDV/SOF) with and without ribavirin (RBV) resulted in 
      high rates of sustained virological response (SVR) in patients chronically 
      infected with genotype 1 hepatitis C virus, including those with compensated 
      cirrhosis. We conducted an analysis of data from these trials to compare the 
      safety and tolerability profile of LDV-SOF with and without RBV. We analyzed 
      treatment-emergent adverse events (AEs) and laboratory abnormalities in patients 
      who were randomized to 8, 12, and 24 weeks of LDV/SOF with or without RBV. In 
      total, data from 1,952 patients (of whom 872 received LDV/SOF with RBV and 1,080 
      received LDV/SOF alone) were analyzed. Overall, 308 patients (16%) were African 
      American, 224 (11%) had compensated cirrhosis, 501 (26%) had a body mass index 
      >/=30 kg/m(2) , and 440 (23%) were treatment experienced. Treatment-related AEs 
      occurred in 71% and 45% of patients treated with and without RBV, respectively, 
      including fatigue, insomnia, irritability, and rash/pruritus. Patients receiving 
      RBV with LDV/SOF were more likely to require dose modification, interruptions of 
      treatment resulting from AEs, or require the use of concomitant medications than 
      those receiving LDV/SOF alone. Rates of treatment-related serious AEs and 
      discontinuations resulting from AEs were similarly low (<1%) in both groups. The 
      rate of SVR in those receiving RBV and those not receiving RBV was the same 
      (97%). CONCLUSION: LDV/SOF plus RBV was associated with a greater incidence of 
      AEs as well as concomitant medication use than LDV/SOF alone. Use of RBV did not 
      impact the efficacy of LDV/SOF regimens in the ION phase III studies.
CI  - (c) 2015 by the American Association for the Study of Liver Diseases.
FAU - Alqahtani, Saleh A
AU  - Alqahtani SA
AD  - Department of Medicine, Johns Hopkins Hospital, Baltimore, MD.
FAU - Afdhal, Nezam
AU  - Afdhal N
AD  - Hepatology, Beth Israel Deaconess Medical Center, Boston, MA.
FAU - Zeuzem, Stefan
AU  - Zeuzem S
AD  - Department of Medicine, Johann Wolfgang Goethe University, Frankfurt, Germany.
FAU - Gordon, Stuart C
AU  - Gordon SC
AD  - Gastroenterology, Henry Ford Health System, Detroit, MI.
FAU - Mangia, Alessandra
AU  - Mangia A
AD  - Department of Hepatology, Casa Sollievo della Sofferenza Hospital, San Giovanni 
      Rotondo, Italy.
FAU - Kwo, Paul
AU  - Kwo P
AD  - Gastroenterology-Hepatology, Indiana University School of Medicine, Indianapolis, 
      IN.
FAU - Fried, Michael
AU  - Fried M
AD  - Liver Center, University of North Carolina Health Care, Chapel Hill, NC.
FAU - Yang, Jenny C
AU  - Yang JC
AD  - Liver Diseases, Gilead Sciences, Inc, Foster City, CA.
FAU - Ding, Xiao
AU  - Ding X
AD  - Liver Diseases, Gilead Sciences, Inc, Foster City, CA.
FAU - Pang, Phillip S
AU  - Pang PS
AD  - Liver Diseases, Gilead Sciences, Inc, Foster City, CA.
FAU - McHutchison, John G
AU  - McHutchison JG
AD  - Liver Diseases, Gilead Sciences, Inc, Foster City, CA.
FAU - Pound, David
AU  - Pound D
AD  - Indianapolis Gastroenterology Research Foundation, Indianapolis, IN.
FAU - Reddy, K Rajender
AU  - Reddy KR
AD  - Division of Gastroenterology, Hospital of the University of Pennsylvania, 
      Philadelphia, PA.
FAU - Marcellin, Patrick
AU  - Marcellin P
AD  - Department of Hepatology, Centre Hospitalier Universitaire Beaujon, 
      Clichy-sous-Bois, France.
FAU - Kowdley, Kris V
AU  - Kowdley KV
AD  - Liver Care Network and Organ Care Research, Swedish Medical Center, Seattle, WA.
FAU - Sulkowski, Mark
AU  - Sulkowski M
AD  - Department of Medicine, Johns Hopkins Hospital, Baltimore, MD.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20150601
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Antiviral Agents)
RN  - 0 (Benzimidazoles)
RN  - 0 (Fluorenes)
RN  - 0 (ledipasvir, sofosbuvir drug combination)
RN  - 49717AWG6K (Ribavirin)
RN  - E2OU15WN0N (Uridine Monophosphate)
RN  - WJ6CA3ZU8B (Sofosbuvir)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antiviral Agents/*therapeutic use
MH  - Benzimidazoles/*therapeutic use
MH  - Drug Therapy, Combination
MH  - Female
MH  - Fluorenes/*therapeutic use
MH  - Genotype
MH  - Hepacivirus/genetics
MH  - Hepatitis C, Chronic/complications/*drug therapy/virology
MH  - Humans
MH  - Liver Cirrhosis/virology
MH  - Male
MH  - Middle Aged
MH  - Ribavirin/*therapeutic use
MH  - Sofosbuvir
MH  - Uridine Monophosphate/*analogs & derivatives/therapeutic use
MH  - Young Adult
EDAT- 2015/05/13 06:00
MHDA- 2015/09/17 06:00
CRDT- 2015/05/13 06:00
PHST- 2015/03/02 00:00 [received]
PHST- 2015/04/15 00:00 [revised]
PHST- 2015/05/07 00:00 [accepted]
PHST- 2015/05/13 06:00 [entrez]
PHST- 2015/05/13 06:00 [pubmed]
PHST- 2015/09/17 06:00 [medline]
AID - 10.1002/hep.27890 [doi]
PST - ppublish
SO  - Hepatology. 2015 Jul;62(1):25-30. doi: 10.1002/hep.27890. Epub 2015 Jun 1.