studies

802A AASLD ABSTRACTS HEPATOLOGY, October, 2015
wave PI, telaprevir (TVR)-based triple therapy of patients with
genotype 1b HCV infection. Methods: In this study, 23 patients
infected with HCV genotype 1b who had not achieved sustained
virologic response (SVR) after TVR-based therapy (17
relapsers, 1 non-responder and 5 patients who discontinued
treatment) received SMV-based therapy at Osaka University
Hospital and institutions participating in the Osaka Liver Forum.
Among them, 19 patients had experienced Peg-IFN plus RBV
therapy (9 relapsers and 10 non-responders) before TVR-based
therapy. Resistance testing of the NS3 region was performed
by ultra-deep sequencing at the start of SMV-based therapy.
Results: In per-protocol, the SVR12 rates were 52% (11/21), 2
patients were non-responders and 8 patients relapsed. The only
factor that was significantly associated with SVR was the virologic
response to Peg-IFN plus RBV (relapser vs. non-responder,
OR: 0.048, p = 0.024, SVR rates: 88% vs 25%) in univariate
analysis, while that to TVR-based therapy had no association
with SVR. Ultra-deep sequencing at the start of SMV-based
therapy revealed that substitution at the R155 position, which
is cross-resistant to TVR and SMV, was detected in only one
patient with low frequency (R155G, 0.4%) and this patient
achieved SVR. RAVs of D168 at the start of SMV-based therapy
were detected in four patients with low frequency (~ 1%). The
SVR rates of patients with and without RAVs of D168 were 50%
(2/4) and 53% (9/17). In two non-response patients for SMVbased
therapy, emergent TVR-resistant variants, V36G (92.2%)
and T54A (82.9%), were undetectable at the start of SMVbased
therapy, but de novo variants of D168 were detected
during the therapy. Conclusions: In this study, no correlation
was observed between baseline RAVs and the effect of SMVbased
therapy. The efficacy of retreatment with SMV-based
therapy after failure of TVR-based therapy was suggested to
depend on previous virologic response to Peg-IFN plus RBV.
Disclosures:
Hayato Hikita - Grant/Research Support: Bristol-Myers Squibb
Tetsuo Takehara - Grant/Research Support: Chugai Pharmaceutical Co., MSD
K.K., Bristol-Meyer Squibb, Mitsubishi Tanabe Pharma Corparation, Toray Industories
Inc. ; Speaking and Teaching: MSD K.K., Bristol-Meyer Squibb, Janssen
Pharmaceutical Companies
The following authors have nothing to disclose: Naoki Morishita, Naoki Hiramatsu,
Tsugiko Oze, Yuki Tahata, Ryoko Yamada, Takayuki Yakushijin, Akira
Yamada, Eiji Mita, Toshihiko Nagase, Yukinori Yamada, Toshifumi Ito, Masahiko
Tsujii, Masami Inada, Yasuharu Imai, Ryotaro Sakamori, Yuichi Yoshida,
Tomohide Tatsumi, Norio Hayashi
1198
Better Work Productivity and Activity in Patients on
Ombitasvir/ Paritaprevir/Ritonavir and Dasabuvir with
or without Ribavirin (3D+RBV or 3D) in Treatment-Naïve
Adults with Genotype 1(GT1) Chronic Hepatitis C
Yan Liu 1 , Yan Luo 1 , Xuan Liu 1 , Danielle Sullivan 1 , Timothy R.
Juday 1 , Brian Conway 2 ; 1 Abbvie Inc, North Chicago, IL; 2 Vancouver
Infectious Diseases Centre, Vancouver, BC, Canada
Background Interferon-containing regimens for treatment of
Chronic Hepatitis C can further worsen the work productivity
and activity impairment (WPAI) of patients. We report the
WPAI of the 311 patients who participated in the phase 3b
MALACHITE-I study. Methods GT1a-infected patients were randomized(2:1)
to receive 12 weeks of 3D+RBV or 12 weeks
of Telaprevir plus peginterferon/ribavirin(TPV+pegIFN+RBV)
and 12-36 additional weeks of pegIFN/RBV. GT1b-infected
patients were randomized(2:2:1) to 3D+RBV, 3D, or TPV+pegIFN/RBV.
Baseline and change from baseline during treatment
and post treatment(PT) periods were measured using
the WPAI instrument (hepatitis C module, WPAI-HCV) for all
five treatment groups The statistical significance of differences
between treatment groups in mean change from baseline to
Week 12 and to PT Week 12 was assessed by subgenotype,
respectively. Results The analyses included 69 patients on
3D+RBV and 34 on TPV+pegIFN/RBV in GT1a, and 84 on
3D+RBV, 83 on 3D and 41 on TPV+pegIFN/RBV in GT1b.
Mean baseline overall work impairment(OWI) and activity
impairment scores for Week 12 and PT Week 12 analyses
varied from 2.5 to 9.1 and 9.3 to 13.4 across treatment
groups. Mean changes from baseline in WPAI-HCV scores
are summarized in the Table. Numerically smaller additional
impairments were observed in OWI at Week 12 with 3D+RBV
in GT1b(p=0.004) and GT1a(p