Of 40 patients with prior treatment data, 10 had failed with boceprevir or telaprevir regimens,. 8/10 due to lack of efficacy. Of 49 patients with complete study drug ...
Poster Session RESULTS: Among patients with available data, median age was 54 years (range, 32–73; n = 56), 44/56 were male, 50/53 white, and 23/29 IL28B non-CC. Most were infected with HCV GT1 (24 1a; 21 1b), with 1 GT2, 7 GT3, and 2 GT4; 12/51 had HIV coinfection, of whom 3 had HIV/HBV coinfection; 4/51 were liver transplant recipients. 31 and 16 of 47 patients were classified as ChildPugh A and B, respectively; of the few (22) with METAVIR scores, 18 had F4. Of 40 patients with prior treatment data, 10 had failed with boceprevir or telaprevir regimens, 8/10 due to lack of efficacy. Of 49 patients with complete study drug data, 48 received DCV+SOF with RBV and 1 received DCV+SOF without RBV. At baseline, HCV RNA levels were high (>800,000 IU/mL) in 10 of 33 patients with available data. Among 11 patients with data at Week 4, HCV RNA was undetectable in 7 and ≤25 IU/mL in another 3; 4 of these 10 patients had previously failed with telaprevir or boceprevir regimens. Adverse events (AEs) were reported in 13 patients; 4 had AEs considered drug-related (opiate withdrawal symptoms, soft tissue infection, vertigo, nausea); none of these drug-related AEs, for which data were available, was serious or led to discontinuation. One patient died due to liver disease progression. Additional data (including updated safety data) for these patients and others will be available for presentation. CONCLUSION: In this preliminary analysis, DCV+SOF RBV demonstrated antiviral activity at Week 4 and was well tolerated in difficult-to-treat patients with severe liver disease and significant risk of hepatic decompensation or death.
P8 Simeprevir with PegIFN/ribavirin for chronic HCV infection shortens time with patientreported symptoms and impairment in QoL: ATTAIN study results J Scott1, K Cerri2, U Sbarigia2, C Corbett3, M Fu4 and W Jessner3 1Janssen Global Services, LLC, High Wycombe, UK, 2
Janssen Pharmaceutica NV, Beerse, Belgium, 3Janssen Research and
Development, Beerse, Belgium, 4Janssen Research and Development, Spring House, USA BACKGROUND: Fatigue, skin and depressive symptoms are
common in chronic hepatitis C virus (HCV)-infected patients, and can impair functioning and quality of life (QoL). ATTAIN, a Phase III, randomised, double-blind study compared simeprevir (SMV) plus peginterferon/ribavirin (PR) versus telaprevir (TVR) plus PR in HCV genotype 1-infected patients with compensated liver disease who were null- or partial-responders to prior PR. Patientreported outcomes (PRO) provide the patient’s perspective on HCV therapy.
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METHODS: Patients received SMV (150 mg once-daily) or TVR (750 mg three-times-daily) plus PR for 12 weeks, then PR alone for 36 weeks. Patients completed PRO questionnaires to rate severity of fatigue [Fatigue Severity Scale (FSS)], skin symptoms (Skindex-16), depressive symptoms [Center for Epidemiologic Studies Depression (CES-D)], work productivity and daily activity impairment (hepatitis C-specific version of Work Productivity and Activity Impairment score, WPAI) and QoL (EuroQoL 5 Dimension, EQ-5D) at baseline (BL) and throughout the study. PRO data analyses compared areaunder-the-curve (BL to Wk60, AUC60; BL to Wk12, AUC12). RESULTS: Mean scores for all PRO scores (763 patients, SMV = 379, TVR = 384) worsened in both groups from BL to Wk12, were generally stable from Wk16 to Wk48 and returned close to BL values from Wk60 onwards. As AUC60 analyses did not show a statistically significant difference between groups in FSS, treatment comparisons for other PRO endpoints were not analysed statistically in keeping with the hierarchical testing procedure specified in the statistical analysis plan. Post-hoc AUC12 analyses significantly favoured SMV versus TVR for FSS (p = 0.003, clinically meaningful difference), WPAI Daily Activity Impairment (p = 0.022), EQ-5D VAS (p < 0.001), and maximum Skindex-16 score (p = 0.0087). Trends for lower CES-D and WPAI Work Impairment scores were observed for AUC12. There were fewer serious adverse events (AEs), treatment-related AEs, AEs leading to permanent stop and anaemia AEs (grade 3 and serious AEs) reported with SMV versus TVR. CONCLUSIONS: During the initial 12-Wk triple treatment period, patients on SMV/PR reported significantly less fatigue and skin symptoms, and less impairment in daily activities and QoL versus TVR/PR patients, consistent with the better safety profile of SMV versus TVR. Significant differences in AUC12 in favour of SMV were not replicated in AUC60 analyses due to longer PR therapy duration, which dominated the overall results.
P9 Efficacy and safety of simeprevir in treatmentna€ıve HCV genotype 1-infected patients with METAVIR F2 fibrosis: QUEST-1 and QUEST-2 Phase III studies M Butı´1, M Manns2, Y Horsmans3, R Flisiak4, G Foster5, V Rafalsky6, M Rizzetto7, R Sarmento-Castro8, M Peeters9, O Lenz9, S Ouwerkerk-Mahadevan10, G De La Rosa11, R Kalmeijer12, M Schlag13 and J Witek12 1Hospital Vall d’Hebron and Ciberhed del Instituto Carlos III, Barcelona, Spain, 2 Medizinische Hochschule Hannover, Hannover, Germany, 3Cliniques Universitaires St Luc, Brussels, Belgium, 4Medical University of Bialystok, Bialystok, Poland, 5Queen Mary, University of London,
© 2014 The Authors Journal of Viral Hepatitis © 2014 Blackwell Publishing Ltd, Vol 21 (Suppl. S2), October 2014, 21–48
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Poster Session
London, UK, 6Smolensk State Medical Academy, Smolensk Oblast, Russia, 7Azienda Ospedaliero Universitaria Molinette San Giovanni Battista di Torino, Torino, Italy, 8Centro Hospitalar do Porto, Porto, Portugal, 9Janssen Infectious Diseases BVBA, Beerse, Belgium, 10
Jansssen Research & Development, Beerse, Belgium,
Services, LLC, Titusville, USA, LLC, Titusville, USA,
12
11
Janssen Global
Janssen Research & Development,
13
Jan-Cil Austria, Vienna, Austria
BACKGROUND: QUEST-1 and QUEST-2 were Phase III, randomised, double-blind studies of simeprevir (SMV), an approved, single-pill, once-daily (QD) HCV NS3/4 protease inhibitor, in combination with PegIFNa-2a (QUEST-1) or PegIFNa-2a/2b (QUEST-2) + RBV (PR) in treatment-na€ıve, HCV genotype (GT)1-infected adults. Treatment in GT1infected patients with moderate fibrosis (METAVIR score F2) is justified based on current recommendations. This post-hoc pooled analysis evaluated the efficacy/safety of SMV/PR in patients with F2 and F3–F4 fibrosis. MATERIALS AND METHODS: Patients (N = 785) received SMV 150 mg QD (12 weeks) + PR (24/48 weeks) or placebo (PBO) (12 weeks) + PR (48 weeks). SMV patients meeting response-guided therapy (RGT) criteria (Week 4 HCV RNA 800,000 IU/mL, 81.1%; GT1a/1b, 50.9/48.6%). 78.5% of F2 SMV/PR patients achieved SVR12 compared with 52.4% of PBO/PR patients. F2 patients had higher response rates than those with F3–F4 scores across various subgroups (Table 1). F2 patients in the SMV/PR group experienced lower on-treatment failure and less relapse than F3–F4 patients (7.7% and 12.8% versus 12.3% and 20.5%, respectively). The most common adverse events (AEs), reported in >25% of SMV/PR F2 patients in the first 12 weeks were fatigue, influenza-like illness and headache. AE incidence was similar with SMV/PR in F2 and F3–F4 patients (Grade 1/2, 70.8% versus 74.6%; Grade 3/4, 24.6% versus 23.1%). Only 1 (0.8%) F2 patient discontinued SMV/PR due
to an AE compared with 4 (3.1%) F3–F4 patients, whilst the incidence of rash was lower in F2 compared with F3–F4 patients (21.0% versus 31.5%). The proportion of patients with pruritus, photosensitivity, neutropenia and anaemia AEs was similar in the two groups (22.6%, 1.6%, 19.4% and 16.1% versus 24.4%, 3.9%, 15.0% and 22.0%, in F2 and F3–F4 patients, respectively). No grade 3/4 haemoglobin decreases were observed in SMV/PR F2 patients. CONCLUSION: Treatment-na€ıve F2 patients treated with SMV/PR achieved higher SVR12 rates than F3–F4 patients, whilst having a similar safety profile and lower discontinuation rates. Most SMV/PR patients were able to complete treatment after 24 weeks. These results support SMV/PR use in patients with moderate fibrosis.
P10 Factors associated with medical resource utilisation and related costs in treatmentexperienced patients with genotype 1 chronic hepatitis C E Akpo1, U Sbarigia2 and J Kleintjens3 1Deloitte, Diegem, Belgium, 2Janssen Pharmaceutica NV, Beerse, Belgium, 3London School of Economics and Political Science, London, UK BACKGROUND: The economic burden associated with
chronic hepatitis C (CHC) virus infection is poorly understood, especially in treatment-experienced patients. The aims of this study were: (i) to investigate which demographics and treatment characteristics drive medical resources utilisation (MRU) and associated costs in treatment-experienced patients with CHC; (ii) to compare differences in MRU-related costs between telaprevir and simeprevir used in combination with pegylated interferon and ribavirin (PegIFN/R). MATERIALS AND METHOD: 643 patients who completed the 72-week ATTAIN trial were included. Costs data were analysed from the UK NHS perspective. Univariate and multivariable regression analyses were performed to deter-
Table 1 P9
SMV/PR group
SVR12 n/N (%)
SVR12 in GT1a pts with Q80K n/N (%)
F2 (N = 130) F3–F4 (N = 130)
102/130 (78.5) 89/130 (68.5)
12/18 (66.7) 14/30 (46.7)
SVR12 in GT1a pts w/o Q80K n/N (%)
SVR12 in GT1b pts n/N (%)
35/45 (77.8) 36/45 (80.0)
54/66 (81.8) 38/54 (70.4)
Met RGT* n/N (%)
Met RGT and achieved SVR12 n/N (%)
Week 4 HCV RNA
