- Email: [email protected]
pibrentasvir in adults with chronic genotype 1–6 hepatitis C virus infection: an integrated analysis
POSTER PRESENTATIONS Results: Mortality rate was 4% (45/1164) and clinical outcomes were seen in 19% (223/1164): hospitalization 11% (131/1164) and emergency room 8% (92/1164). Charlson Index was higher in patients with outcomes (3.3 ± 1.8 vs. 2.3 ± 1.6; p < 0.0001) and exitus (4.4 ± 2.4 vs. 2.4 ± 1.6; p < 0.0001). Age (59.4 ± 11.7 vs. 57.1 ± 10.1 years; p = 0.008), albumin (3.7 ± 0.6 vs. 4 ± 0.5 mg/dl; p = 0.0001), bilirubin (1.33 ± 1.3 vs. 1.03 ± 0.8; p = 0.0001), MELD (10.4 ± 3.8 vs. 8.6 ± 2.5; p = 0.0001) and decompensated cirrhosis (43% (95/223) vs. 14% (128/941); p = 0.0001) were associated in the univariate analysis with clinical outcomes. In multivariate analysis, age [HR 1.02 (95% CI 1.00–1.03); p = 0.015], albumin [HR 0.52 (95% CI 0.41–0.65); p = 0.0001] and CI [HR 1.20 (95% CI 1.13–1.28); p = 0.0001] were independently related to clinical outcomes. Moreover, CI [HR 1.43 (95% CI 1.26–1.62); p = 0.0001], age [HR 1.10 (95% CI 1.06–1.13); p = 0.0001], bilirubin [HR 1.3 (95% CI 1.04– 1.62); p = 0.022], albumin [HR 0.25 (95% CI 0.15–0.42); p = 0.0001] and ALT [HR 0.99 (95% CI 0.98–0.99); p = 0.022] were independently related to death. Data mining and decision tree allowed us to build an algorithm for the prediction of clinical outcomes and mortality taking into account CI and albumin level (Figure).
In a large registrational program, G/P achieved sustained virologic response rates of ≥95% and low rates of virologic failures in most populations evaluated across all major GTs. We report the integrated safety results from patients enrolled in phase 2 or 3 studies. Methods: Key inclusion criteria from 8 multicenter, phase 2 or 3 clinical trials included in this analysis were age ≥18 years, compensated liver disease, and treatment-naïve or treatmentexperienced status. Exclusion criteria were hepatitis B virus coinfection and creatinine clearance <50 mL/min. Patients received G/P 300/120 mg once daily for 8, 12, or 16 weeks. Adverse events (AEs) and laboratory abnormalities were monitored. Results: Of the 2265 patients in the analysis, 288 (12.7%) had compensated cirrhosis, while 1977 (87.3%) did not have cirrhosis. AEs occurring in ≥10% of subjects were headache and fatigue (Table). Most AEs were mild (65.9%), and the frequency and severity of AEs were similar in subjects with cirrhosis and subjects without cirrhosis. Frequency of grade ≥3 AEs, AEs leading to discontinuation of study drug, and serious AEs were 2.9%, 0.4%, and 2.1%, respectively. Grade ≥3 laboratory abnormalities were infrequent (≤0.4%). No cases consistent with drug-induced liver injury occurred. Table: AEs Event DAA-related AEs Any Serious AE AE grade ≥3 AE leading to discontinuation of study drug Most frequent AEs (≥10%) Headache Fatigue
Conclusions: Baseline co-morbidities and liver dysfunction were strongly related to clinical outcomes and mortality in patients with hepatitis C receiving DAA therapy. An algorithm based on Charlson Index and albumin identifies patients at risk of clinical outcomes or death beyond sustained viral eradication. FRI-238 Safety of glecaprevir/pibrentasvir in adults with chronic genotype 1–6 hepatitis C virus infection: an integrated analysis J.-F. Dufour1, E. Zuckerman2, N. Zadeikis3, C. Hezode4, S.W. Paik5, P. Andreone6, O. Weiland7, J. Slim8, S.L. Flamm9, T. Morgan10, H. Vargas11, S. Strasser12, A. Brown13, Y. Yu3, A. Porcalla3, F. Mensa3. 1 University Clinic for Visceral Surgery and Medicine, Inselspital, Bern, Switzerland; 2Carmel Medical Center Liver Institute, Haifa, Israel; 3 AbbVie, North Chicago, IL, United States; 4Hôpital Henri Mondor, Université Paris-Est, Créteil, France; 5Samsung Medical Center, Seoul, South Korea; 6Dipartimento di Scienze Mediche e Chirurgiche, University of Bologna, Bolongna, Italy; 7Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden; 8St. Michael’s Medical Center, Newark, NJ; 9Northwestern Feinberg School of Medicine, Chicago, IL; 10 Veteran’s Affairs Long Beach Healthcare System, Long Beach, CA; 11 Mayo Clinic, Phoenix, AZ, United States; 12Royal Prince Alfred Hospital, Sydney, Australia; 13Imperial College Healthcare, London, United Kingdom E-mail: [email protected] Background and Aims: The direct-acting antivirals (DAAs) glecaprevir (an NS3/4 protease inhibitor identified by AbbVie and Enanta) and pibrentasvir (an NS5A inhibitor) were developed as a combination regimen (G/P) to treat adults with chronic hepatitis C virus (HCV) infection due to genotypes (GTs) 1–6 with compensated liver disease.
Overall, n (%) N = 2265 929 (41.0) 1 (<0.1) 4 (0.2) 3 (0.1)
410 (18.1) 330 (14.6)
Conclusions: In patients with HCV GT1–6 infection, G/P was well tolerated in subjects with compensated liver disease, with mostly mild AEs, low rates of serious AEs and treatment discontinuation. Ontreatment laboratory abnormalities were rare, and patterns and rates of AEs were similar in subjects with and those without compensated cirrhosis. G/P was not associated with drug-induced liver injury. FRI-239 Analysis of the real-world treatment effectiveness of elbasvir/ grazoprevir J.S. Mc Combs1, J. McGinnis1, S. Fox2, I. Tonnu-Mihara3. 1School of Pharmacy; 2Keck School of Medicine, University of Southern California, Los Angeles; 3Department of Veterans Affairs, Veterans Health Administration, Long Beach, United States E-mail: [email protected] Background and Aims: Documentation of the real-world effectiveness of elbasvir/grazoprevir, a new all-oral direct acting antiviral (DAA) treatment for hepatitis C, is limited. This study evaluated the effectiveness of elbasvir/grazoprevir for the treatment of hepatitis C patients within the Veterans Health Administration. Methods: A retrospective cohort study was conducted using patients who initiated treatment on elbasvir/grazoprevir and terminated treatment prior to August 1, 2016. This restriction allowed for a posttreatment observation period of at least 12 weeks in which to determine if the patient completed adequate post-treatment viral load lab tests to determine treatment outcome. The primary outcome measure was a sustained virolgic response at 12-weeks posttreatment (SVR12). Patients were designated as achieving SVR12 if all of their post-treatment viral load lab results were “not detected” with one lab test occurring 12 or more weeks following termination of treatment. Results: A total of 929 elbasvir/grazoprevir patients terminate treatment before August 1, 2016 of which 732 patients had at least one post-treatment viral load test. Of those, 548 patients had
Journal of Hepatology 2017 vol. 66 | S333–S542
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In a large registrational program, G/P achieved sustained virologic response rates of ≥95% and low rates of virologic failures in most populations evaluated across all major GTs. We report the integrated safety results from patients enrolled in phase 2 or 3 studies. Methods: Key inclusion criteria from 8 multicenter, phase 2 or 3 clinical trials included in this analysis were age ≥18 years, compensated liver disease, and treatment-naïve or treatmentexperienced status. Exclusion criteria were hepatitis B virus coinfection and creatinine clearance <50 mL/min. Patients received G/P 300/120 mg once daily for 8, 12, or 16 weeks. Adverse events (AEs) and laboratory abnormalities were monitored. Results: Of the 2265 patients in the analysis, 288 (12.7%) had compensated cirrhosis, while 1977 (87.3%) did not have cirrhosis. AEs occurring in ≥10% of subjects were headache and fatigue (Table). Most AEs were mild (65.9%), and the frequency and severity of AEs were similar in subjects with cirrhosis and subjects without cirrhosis. Frequency of grade ≥3 AEs, AEs leading to discontinuation of study drug, and serious AEs were 2.9%, 0.4%, and 2.1%, respectively. Grade ≥3 laboratory abnormalities were infrequent (≤0.4%). No cases consistent with drug-induced liver injury occurred. Table: AEs Event DAA-related AEs Any Serious AE AE grade ≥3 AE leading to discontinuation of study drug Most frequent AEs (≥10%) Headache Fatigue
Conclusions: Baseline co-morbidities and liver dysfunction were strongly related to clinical outcomes and mortality in patients with hepatitis C receiving DAA therapy. An algorithm based on Charlson Index and albumin identifies patients at risk of clinical outcomes or death beyond sustained viral eradication. FRI-238 Safety of glecaprevir/pibrentasvir in adults with chronic genotype 1–6 hepatitis C virus infection: an integrated analysis J.-F. Dufour1, E. Zuckerman2, N. Zadeikis3, C. Hezode4, S.W. Paik5, P. Andreone6, O. Weiland7, J. Slim8, S.L. Flamm9, T. Morgan10, H. Vargas11, S. Strasser12, A. Brown13, Y. Yu3, A. Porcalla3, F. Mensa3. 1 University Clinic for Visceral Surgery and Medicine, Inselspital, Bern, Switzerland; 2Carmel Medical Center Liver Institute, Haifa, Israel; 3 AbbVie, North Chicago, IL, United States; 4Hôpital Henri Mondor, Université Paris-Est, Créteil, France; 5Samsung Medical Center, Seoul, South Korea; 6Dipartimento di Scienze Mediche e Chirurgiche, University of Bologna, Bolongna, Italy; 7Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden; 8St. Michael’s Medical Center, Newark, NJ; 9Northwestern Feinberg School of Medicine, Chicago, IL; 10 Veteran’s Affairs Long Beach Healthcare System, Long Beach, CA; 11 Mayo Clinic, Phoenix, AZ, United States; 12Royal Prince Alfred Hospital, Sydney, Australia; 13Imperial College Healthcare, London, United Kingdom E-mail: [email protected] Background and Aims: The direct-acting antivirals (DAAs) glecaprevir (an NS3/4 protease inhibitor identified by AbbVie and Enanta) and pibrentasvir (an NS5A inhibitor) were developed as a combination regimen (G/P) to treat adults with chronic hepatitis C virus (HCV) infection due to genotypes (GTs) 1–6 with compensated liver disease.
Overall, n (%) N = 2265 929 (41.0) 1 (<0.1) 4 (0.2) 3 (0.1)
410 (18.1) 330 (14.6)
Conclusions: In patients with HCV GT1–6 infection, G/P was well tolerated in subjects with compensated liver disease, with mostly mild AEs, low rates of serious AEs and treatment discontinuation. Ontreatment laboratory abnormalities were rare, and patterns and rates of AEs were similar in subjects with and those without compensated cirrhosis. G/P was not associated with drug-induced liver injury. FRI-239 Analysis of the real-world treatment effectiveness of elbasvir/ grazoprevir J.S. Mc Combs1, J. McGinnis1, S. Fox2, I. Tonnu-Mihara3. 1School of Pharmacy; 2Keck School of Medicine, University of Southern California, Los Angeles; 3Department of Veterans Affairs, Veterans Health Administration, Long Beach, United States E-mail: [email protected] Background and Aims: Documentation of the real-world effectiveness of elbasvir/grazoprevir, a new all-oral direct acting antiviral (DAA) treatment for hepatitis C, is limited. This study evaluated the effectiveness of elbasvir/grazoprevir for the treatment of hepatitis C patients within the Veterans Health Administration. Methods: A retrospective cohort study was conducted using patients who initiated treatment on elbasvir/grazoprevir and terminated treatment prior to August 1, 2016. This restriction allowed for a posttreatment observation period of at least 12 weeks in which to determine if the patient completed adequate post-treatment viral load lab tests to determine treatment outcome. The primary outcome measure was a sustained virolgic response at 12-weeks posttreatment (SVR12). Patients were designated as achieving SVR12 if all of their post-treatment viral load lab results were “not detected” with one lab test occurring 12 or more weeks following termination of treatment. Results: A total of 929 elbasvir/grazoprevir patients terminate treatment before August 1, 2016 of which 732 patients had at least one post-treatment viral load test. Of those, 548 patients had
Journal of Hepatology 2017 vol. 66 | S333–S542
S515