studies

766A AASLD ABSTRACTS HEPATOLOGY, October, 2015
Table 1. Mean changes in clinical parameters through Week 12
on treatment
Disclosures:
Paul Martin - Advisory Committees or Review Panels: BMS; Grant/Research
Support: Merck, Gilead, Janssen, Abbvie
Edward J. Gane - Advisory Committees or Review Panels: Novira, AbbVie, Janssen,
Gilead Sciences, Janssen Cilag, Achillion, Merck, Tekmira; Speaking and
Teaching: AbbVie, Gilead Sciences, Merck
Lin Liu - Employment: Gilead Sciences, Inc.
Karim Sajwani - Employment: Gilead Sciences, Inc.
Brian Kirby - Employment: Gilead Sciences
Jill M. Denning - Employment: Gilead Sciences, Inc.
Luisa M. Stamm - Employment: Gilead Sciences
Diana M. Brainard - Employment: Gilead Sciences; Stock Shareholder: Gilead
Sciences
John G. McHutchison - Employment: Gilead Sciences; Stock Shareholder: Gilead
Sciences
Eric Lawitz - Advisory Committees or Review Panels: AbbVie, Achillion Pharmaceuticals,
Regulus, Theravance, Enanta, Idenix Pharmaceuticals, Janssen, Merck
& Co, Novartis, Gilead; Grant/Research Support: AbbVie, Achillion Pharmaceuticals,
Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmith-
Kline, Idenix Pharmaceuticals, Intercept Pharmaceuticals, Janssen, Merck & Co,
Novartis, Nitto Denko, Theravance, Salix, Enanta; Speaking and Teaching: Gilead,
Janssen, AbbVie, Bristol Meyers Squibb
Stuart C. Gordon - Advisory Committees or Review Panels: Janssen; Consulting:
Merck, Gilead, BMS, CVS Caremark, Amgen, AbbVie; Grant/Research Support:
Merck, Gilead, AbbVie, Intercept Pharmaceuticals, Exalenz Sciences, Inc., BMS
The following authors have nothing to disclose: Grisell Ortiz-Lasanta, Richard
A. Robson
1129
A Meta-Analysis of the Association Between Pre-Treatment
Variables and SVR Amongst Genotype 1 Patients
Treated with ABT-450/r–Ombitasvir and Dasabuvir
(VIEKIRA PAK) plus Ribavirin for 12 Weeks
Gregory J. Botwin 2 , Timothy R. Morgan 1,3 ; 1 Gastroenterology (11),
VA Long Beach Healthcare System, Long Beach, CA; 2 Research
Service, VA Long Beach Healthcare System, Long Beach, CA;
3 Division of Gastroenterology, University of California - Irvine,
Irvine, CA
Background: VIEKIRA PAK plus Ribavirin (RBV) is a potent, all
oral, treatment regimen indicated for the treatment of chronic
hepatitis C (HCV) genotype (GT)-1. Due to the overall high
rates of sustained virologic response (SVR) achieved in Phase
II and Phase III clinical trials, little is known about the association
between pre-treatment variables and SVR. Purpose: To
perform a meta-analysis to examine the association between
pre-treatment variables and SVR in GT-1 patients. Methods:
We reviewed all registration trials for VIEKIRA PAK. Trials
that treated GT-1a, or GT-1a and GT-1b, monoinfected, non-cirrhotic,
HCV patients for 12 weeks with VIEKIRA PAK plus
RBV were included in our initial analysis. Trials that enrolled
exclusively GT-1b patients were excluded due to the overall
high SVR rates. Relative risk (RR) was calculated for the following
pre-treatment variables: age, body-mass index (BMI), ethnicity,
IL28B, race, sex, and viral load (VL). A binary random
effects model was used in the meta-analysis. Results: Three
studies (SAPPHIRE-I and II, and PEARL-IV) and 870 patients met
the criteria. Of the evaluated patients 595 were genotype 1a,
and 297 were treatment experienced. Compared with patients
with a BMI < 30, a BMI ≥ 30 was associated with a reduced
RR of SVR, 0.948 (95% confidence-interval [CI], 0.903-0.995,
p=0.029). The overall SVR in each group was 92% (139/151;
BMI ≥ 30) and 97% (699/719; BMI < 30). Patients with a VL
≥ 800,000IU/mL (SVR 96%, 686/716) also had a reduced
RR of SVR, 0.973 (CI 0.948-0.999, p=0.041) compared to
patients with a VL below this level (SVR 99%, 152/154). Neither
age < 55 years, Hispanic ethnicity, IL28B CC genotype,
African American race, nor male sex were found to be significantly
positively or negatively associated with SVR. When
380 GT-1 cirrhotic patients, treated for 12 or 24 weeks (TUR-
QUOISE-II) were included in the analysis, only BMI remained
significantly associated with SVR (RR 0.956, CI 0.921-0.993,
p=0.021). Conclusion: Genotype 1 non-cirrhotic patients with
an elevated BMI or VL are associated with a reduced chance
of achieving SVR when treated with VIEKIRA PAK plus RBV
for 12 weeks. Research evaluating the mechanism for these
differences may be warranted.
Pre-Treatment Variables Association with SVR
Disclosures:
Timothy R. Morgan - Grant/Research Support: Merck, Abbvie, Genentech, Gilead,
Bristol Myers Squibb
The following authors have nothing to disclose: Gregory J. Botwin
1130
On-treatment HCV RNA Decline in Pre-and Post-Liver
Transplant Patients with Different Degrees of Fibrosis
and Cirrhosis: a combined analysis of the SOLAR trials
Tania M. Welzel 1 , K. Rajender Reddy 2 , Michael P. Manns 3 , Steven
L. Flamm 4 , David J. Mutimer 5 , Edward J. Gane 6 , Robert H.
Hyland 7 , Ming Lin 7 , Phillip S. Pang 7 , John G. McHutchison 7 , Didier
Samuel 8 , Michael R. Charlton 9 , Xavier Forns 10 , Gregory T. Everson
11 , Stefan Zeuzem 1 , Nezam H. Afdhal 12 ; 1 Johann Wolfgang
Goethe University Medical Center, Frankfurt am Main, Germany;
2 University of Pennsylvania School of Medicine, Philadelphia, PA;
3 Hannover Medical School, Hannover, Germany; 4 Northwestern
University Feinberg School of Medicine, Chicago, IL; 5 Queen Elizabeth
Hospital and University of Birmingham, Birmingham, United
Kingdom; 6 University of Auckland, Auckland, New Zealand; 7 Gilead
Sciences, Inc, Foster City, CA; 8 Université Paris-Sud, Villejuif,
France; 9 Intermountain Medical Center, Murray, UT; 10 Liver
Unit, IDIBAPS and CIBEREHD, Barcelona, Spain; 11 University of
Colorado Denver, Aurora, CO; 12 Beth Israel Deaconess Medical
Center, Boston, MA
Background and Aims: In the SOLAR-1 and SOLAR-2 studies,
ledipasvir/sofosbuvir (LDV/SOF)+ribavirin (RBV) for 12 or 24
weeks resulted in high SVR rates in genotype 1 or 4 HCV-infected
patients with decompensated cirrhosis or who were liver
transplant recipients. In this large combined post hoc analysis
of on-treatment HCV RNA levels in SOLAR-1 and SOLAR-2 study
participants we investigate whether on-treatment response varied
by patient population and/or was predictive of treatment
outcome. Methods: Data from the identically designed SOLAR1
(NCT01938430) and SOLAR 2 (NCT02010255) studies were
combined. Six groups of genotype 1 or 4 HCV-infected patients
were randomized to receive 12 or 24 weeks of LDV/SOF+RBV
treatment: patients without transplant and either 1) Child-Pugh-
Turcotte (CPT) B cirrhosis, or 2) CPT C cirrhosis; or patients
who have undergone transplantation and who were either 3)
without cirrhosis (F0 to F3), 4) CPT A cirrhosis, 5) CPT B cirrhosis,
or 6) CPT C cirrhosis. Patients with FCH were excluded