studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 771A
Harald Hofer - Advisory Committees or Review Panels: Gilead, Abbvie; Speaking
and Teaching: Janssen, BMS, Gilead, Abbvie
The following authors have nothing to disclose: Karin Kozbial, Albert Stättermayer,
Clarissa Freissmuth, Rafael Stern, Sandra Beinhardt, Christian Rechling,
Petra E. Steindl-Munda
1138
Association between severe rash and HLA polymorphism
in telaprevir-based triple therapy for chronic hepatitis
C in a multi-centric study in Japan
Yoko Yamagiwa 1 , Naohiko Masaki 1 , Nao Nishida 1 , Minae
Kawashima 2 , Seik-Soon Khor 2 , Hiroko Miyadera 1 , Masaya Sugiyama
1 , Masaaki Korenaga 1 , Kazumoto Murata 1 , Tatsuya Kanto 1 ,
Yasuhito Tanaka 3 , Kazuhiko Koike 4 , Katsushi Tokunaga 2 , Masashi
Mizokami 1 ; 1 The Research Center for Hepatitis and Immunology,
National Center for Global Health and Medicine, Ichikawa, Japan;
2 Department of Human Genetics, Graduate School of Medicine
The University of Tokyo, Tokyo, Japan; 3 Department of Virology
and Liver Unit, Nagoya City University Graduate School of Medical
Sciences, Nagoya, Japan; 4 Department of Gastroenterology,
The University of Tokyo, Tokyo, Japan
Background and Aim Although telaprevir (TVR) enabled a
remarkable improvement in efficacy of interferon treatment
for chronic hepatitis C, it had serious adverse events such as
dermatological adverse events which required discontinuance
of treatment in serious grade of rash which was potentially
life-threatening. However, mechanism of severe rash in TVRbased
therapy has not been clarified yet. Thus, we aimed to
identify genetic risk factors associated with serious grade of
rash. Methods and Results Genome-wide association study
(GWAS) was performed in 384 patients received TVR combined
with ribavirin and peg-interferon using Affymetrix
AXIOM ASI arrays. We compared allele frequency of each single
nucleotide polymorphism (SNP) between 182 patients who
did not experience skin eruption and 50 patients with grade 3
of rash defined by rash over 50% of body surface area, rash
with additional changes such as vesicles, or with systematic
reaction such as fever. However, no significant association
was identified in the GWAS stage. Next, SNP imputation and
association testing was performed using PLINK in 141 SNPs
with p < 1.00E-05 in the GWAS stage. As a result, 22 out
of 25 SNPs with p < 1.00E-06 in the SNP imputation, were
located in the human leukocyte antigen (HLA) region on chromosome
6. Finally, statistical imputation analysis of classical
HLA alleles was performed in the SNP data using HIBAG R
package optimized for Japanese population (Pharmacogenomics
J. 2015). HLA-DRB1*09:01 showed a significant association
with an odds ratio (OR) of 3.376 (p = 9.12E-06) and
HLA-DQB1*03:03, which is known to be in strong linkage
disequilibrium with DRB1*09:01 in the Japanese population,
also showed a significant association with an OR of 2.907 (p
= 7.15E-05). Discussion and Conclusions More frequent severe
rash in phase III trial in Japan (9%) compared with that in the
USA and Europe (5%), may related with higher frequency of
HLA-DRB1*09:01 in Japanese population than in Caucasian
(15% vs 1%). Genetic variants located in the HLA region in
Japanese should be candidate genetic factors in susceptibility
to severe rash in TVR-based triple therapy.
Disclosures:
Yasuhito Tanaka - Grant/Research Support: Chugai Pharmaceutical CO., LTD.,
MSD, Bristol-Myers Squibb; Speaking and Teaching: janssen pharma, Bristol-Myers
Squibb
The following authors have nothing to disclose: Yoko Yamagiwa, Naohiko
Masaki, Nao Nishida, Minae Kawashima, Seik-Soon Khor, Hiroko Miyadera,
Masaya Sugiyama, Masaaki Korenaga, Kazumoto Murata, Tatsuya Kanto,
Kazuhiko Koike, Katsushi Tokunaga, Masashi Mizokami
1139
Patient Reasons for Initiating or Delaying Hepatitis C
Virus (HCV) Treatment and Physician Reasons for Selecting
an HCV Treatment: A Prospective Observational
Study
Shelagh M. Szabo 2 , David R. Walker 1 , Timothy R. Juday 1 ,
Suzanne Lane 2 , Sammy Saab 3 ; 1 HEOR, Abbvie, North Chicago,
IL; 2 Icon Health Economics, Vancouver, BC, Canada; 3 David Geffen
School of Medicine, UCLA, Los Angeles, CA
BACKGROUND This is a prospective, multicenter observational
study of humanistic and economic outcomes among patients
initiating direct acting antiviral treatments for hepatitis C virus
(HCV). The objective of this analysis is to describe patient reasons
for treatment delay or initiation and physician reasons
for selection of a specific treatment regimen. METHODS All
consecutive HCV patients attending clinics at ten sites in the
United States were screened to identify the cohort initiating
treatment for HCV. From that cohort, data were collected using
patient-completed surveys at up to five time points over the treatment
course, supplemented by a medical chart review at treatment
initiation and completion. Type of data collected included
demographic, clinical, economic, and humanistic, however, for
this analysis, only screening data were used. Data on patients’
reasons for initiating or delaying treatment, and physicians’
reasons for recommending treatment were collected; multiple
responses were allowed per patient. The first patient enrolled
January 2013 and the last patient enrolled September 2014.
RESULTS There were 143 patients, from eight clinics, enrolled
in the study out of the 787 that were screened across ten clinics.
Among enrolled patients, 137 were from community clinics
and 6 were from academic/hospitals. The mean age was 56
years, 52% male, 60% white, 20% Hispanic and 15% black.
75% graduated from high school and 33% were employed.
100 patients were on a sofosbuvir and/or simeprevir-based
regimen, and 43 patients were on other treatments. 50% were
on an interferon-free regimen. Patient-reported reasons for initiating
treatment were desire to be cured (74.1%), physician’s
recommendation (70.6%), to prevent future liver damage
(62.2%), peace of mind (49%), to manage HCV symptoms
(31.5%), worry about transmission (26.6%), to avoid social
stigma (10.5%), desire to have children (7.7%), family pressure
(6.3%), and other (2.8%). Patient-reported reasons for initially
delaying treatment were physician recommendation (23.8%),
waiting for the availability of new treatments (21.0%), no or
mild symptoms (17.5%), cost (9.1%), health conditions other
than HCV (5.6%) and other (39.2%). The primary physician-reported
reason for selection of a specific treatment regimen was
likelihood of treatment success (83.9%), followed by tolerability
(7.7%), reimbursement/access (2.8%), co-pay (0%), and other
(4.9%). CONCLUSIONS The potential for achieving cure was
the most important reason for a physician choosing a specific
HCV treatment regimen. Cost however, did not play an important
role for treatment selection or delay for physicians and
patients, respectively.
Disclosures:
Shelagh M. Szabo - Employment: Oxford Outcomes
David R. Walker - Employment: Abbvie; Stock Shareholder: Abbvie, Baxter
Healthcare
Timothy R. Juday - Employment: AbbVie; Stock Shareholder: AbbVie
Sammy Saab - Advisory Committees or Review Panels: BMS, Gilead, Merck,
Janssen; Grant/Research Support: Gilead; Speaking and Teaching: BMS, Gilead,
Merck, Janssen, Salix, Onyx, Bayer, Janssen; Stock Shareholder: Achillion,
Johnson and Johnson, BMS, Gilead
The following authors have nothing to disclose: Suzanne Lane