studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 565A
The following authors have nothing to disclose: Velimir A. Luketic
716
An integrated safety analysis of daclatasvir + sofosbuvir,
with or without ribavirin, in patients with chronic
HCV infection
Charles S. Landis 1 , David R. Nelson 2 , Mark S. Sulkowski 3 , Peter
J. Ruane 4 , Anthony M. Mills 5 , Fred Poordad 6 , David L. Wyles 7 ,
Rafia Bhore 8 , Peter Ackerman 9 , Khurram Rana 9 , Eugene S. Swenson
9 , Stephanie Noviello 8 ; 1 University of Washington School of
Medicine, Seattle, WA; 2 University Of Florida, Gainesville, FL;
3 Johns Hopkins University, Baltimore, MD; 4 Ruane Medical and
Liver Health Institute, Los Angeles, CA; 5 Anthony Mills MD, Inc,
Los Angeles, CA; 6 Texas Liver Institute, University of Texas Health
Sciences, San Antonio, TX; 7 University of California, San Diego,
CA; 8 Bristol-Myers Squibb, Princeton, NJ; 9 Bristol-Myers Squibb,
Wallingford, CT
Background: The pangenotypic combination of daclatasvir
(DCV) and sofosbuvir (SOF), with or without ribavirin (RBV),
has achieved high SVRs (82%–98%) in multiple patient populations
with HCV infection. We evaluated the safety of DCV+-
SOF±RBV by pooling individual patient data from phase 2 and
3 studies. Methods: Data were derived from treatment-naive
or -experienced patients with HCV infection and advanced
cirrhosis or post-transplant recurrence (ALLY-1), HIV/HCV coinfection
(ALLY-2), HCV genotype (GT) 3 infection (ALLY-3), and
chronic HCV infection (AI444-040). Overall, 679 patients
received DCV+SOF±RBV for 8, 12, or 24 weeks. Pooled
data were analyzed for on-treatment adverse events (AEs),
serious AEs, AE-related discontinuations, and grade 3/4 AEs
and lab abnormalities. Results: Patients were 67% male, 80%
white/16% black, 62% naive; median age was 55 years and
18% had cirrhosis, of whom half had hepatic decompensation
(Child-Pugh class B and C). 49% of patients had HCV
GT1a infection, 13% GT1b, 7% GT2, 30% GT3, 1% GT4,
0.1% GT6. Overall, 98% of patients completed treatment.
The most common AEs (any grade) were fatigue, headache,
and nausea. Serious AEs, grade 3/4 AEs, and AE-related discontinuations
were infrequent but more common in patients
receiving RBV (Table); few were treatment-related. All 4 deaths
were posttreatment and unrelated. Safety with DCV+SOF was
comparable in patients with or without compensated cirrhosis.
DCV+SOF+RBV patients with cirrhosis, most with hepatic
decompensation, had slightly higher rates of serious AEs, anemia,
and liver-related lab abnormalities than those without
cirrhosis. There were few safety signals in this diverse population
receiving a broad range of concomitant medications,
including antiretroviral and immunosuppressive agents. Conclusion:
DCV+SOF±RBV is associated with low rates of safety
events. The presence of GT3 infection, HIV/HCV coinfection,
advanced cirrhosis, or post-transplant HCV recurrence has minimal
impact on safety, suggesting that DCV+SOF±RBV is a safe
and well-tolerated treatment for a broad range of patients with
chronic HCV infection.
a
ALLY-2, ALLY-3, AI444040
b
ALLY-1, AI444040
c
Includes ALLY-1 post-transplant patients with cirrhosis status
missing
d
Excludes 5 patients with study drug overdoses reported as SAEs
Disclosures:
Charles S. Landis - Grant/Research Support: Gilead, Abbvie, BMS
David R. Nelson - Advisory Committees or Review Panels: Merck; Grant/Research
Support: Abbot, BMS, Beohringer Ingelheim, Gilead, Genentech, Merck, Bayer,
Idenix, Vertex, Jansen
Mark S. Sulkowski - Advisory Committees or Review Panels: Merck, AbbVie,
Janssen, Gilead, BMS; Grant/Research Support: Merck, AbbVie, Janssen, Gilead,
BMS
Peter J. Ruane - Advisory Committees or Review Panels: BMS; Consulting: Gilead,
Abbvie, Janssen; Grant/Research Support: BMS, Gilead, Merck, Abbvie, Idenix,
Idenix, Janssen, Viiv; Speaking and Teaching: Gilead, Merck, Abbvie, Abbvie,
Janssen; Stock Shareholder: Gilead, Gilead
Anthony M. Mills - Advisory Committees or Review Panels: Gilead, ViiV, Merck;
Grant/Research Support: Gilead, ViiV, Merck, BMS; Speaking and Teaching:
Gilead
Fred Poordad - Advisory Committees or Review Panels: Abbott/Abbvie, Achillion,
BMS, Inhibitex, Boeheringer Ingelheim, Pfizer, Genentech, Idenix, Gilead,
Merck, Vertex, Salix, Janssen, Novartis; Grant/Research Support: Abbvie,
Anadys, Achillion, BMS, Boehringer Ingelheim, Genentech, Idenix, Gilead,
Merck, Pharmassett, Vertex, Salix, Tibotec/Janssen, Novartis
David L. Wyles - Advisory Committees or Review Panels: Bristol Myers Squibb,
Janssen, Merck; Grant/Research Support: Gilead, Merck, Bristol Myers Squibb,
AbbVie, Tacere
Peter Ackerman - Employment: Bristol-Myers, Squibb
Khurram Rana - Employment: Bristol-Myers Squibb
Eugene S. Swenson - Employment: Bristol-Myers Squibb
Stephanie Noviello - Consulting: Merck/Schering-Plough; Employment: Bristol-Myers
Squibb, Merck/Schering-Plough; Stock Shareholder: Merck/Schering-Plough,
J&J
The following authors have nothing to disclose: Rafia Bhore
717
C-EDGE TN: Impact Of 12-Week Oral Regimen Of Grazoprevir
(GZR, MK-5172)/Elbasvir (EBR, MK-8742) On
Patient-Reported Outcomes (PROs) In Treatment-Naïve
Patients With Chronic Hepatitis C Virus (HCV) Genotype
(GT) 1, 4, Or 6 Infection
Jean Marie Arduino, Yang Wang, Deborah D. Brown, Shazia
Khawaja, Elisa Martinez, Joan R. Butterton, Michael Robertson,
Chizoba Nwankwo, T. Christopher Mast; Merck & Co., Inc.,
Kenilworth, NJ
Background:Chronic HCV infection negatively impacts patients’
health and well-being.A Phase 3, double-blind, placebo-control,
randomized trial of an oral fixed-dosed combination of GZR
100 mg/EBR 50 mg once daily for 12 weeks was conducted
among HCV GT1-,4-,or 6-infected patients.GZR/EBR was highly
effective (SVR12:94.6%(95% CI: 91.5,96.8%)) and generally
well-tolerated,with a similar safety profile to placebo.Our aim
was to evaluate whether HCV treatment with GZR/EBR altered
PROs.Methods:Subjects completed 5 PROs at baseline, treatment
week 4 (TW4),TW12, follow-up week 4(FW4):SF-36v2®,
EQ-VAS,FACIT-Fatigue Scale,Chronic Liver Disease Question-