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Su1428 Daclatasvir and Sofosbuvir Therapy for Patients with Decompensated Cirrhosis or Post-Liver Transplant HCV Recurrence and Advanced Fibrosis or Cirrhosis: United States Multicenter Treatment Protocol
median age, 58 years; 63% (n = 199) male; 61% (n = 191) white; 34% (n = 108) black; 15% (n = 46) Hispanic/Latino; 72% (n = 226) genotype 1a; 21% (n = 67) genotype 1b. Overall, 92% (n = 291) received simeprevir + sofosbuvir; 5% (n = 17) simeprevir + sofosbuvir + ribavirin; 2% (n = 7) simeprevir + peginterferon + ribavirin. The distribution of patients at practice settings was: academic medical center, 20% (n = 62); private practice, 63% (n = 199); integrated health network, 10% (n = 31). At baseline, 30% (n = 95) were treatmentexperienced; 39% (n = 124) had cirrhosis; 13% (n = 41) had hepatic decompensation. 1% (4/311) reported having 8-14 drinks/week and 13% (39/311) having <8 drinks/week; 25% (78/311) annual household income <$10,000 US dollars. 124 patients with cirrhosis and 191 patients without cirrhosis received simeprevir for a median duration of 12 weeks. Virologic response data are shown (Table). Most common adverse events (AEs) were headache (13%), fatigue (13%), and nausea (11%); 9% of patients had a serious AE, none were related to simeprevir treatment. Conclusions: In this analysis, use of simeprevir + sofosbuvir was common and 92% of patients on this regimen (excluding non-virologic failures) achieved SVR12. Simeprevir-based treatment was well tolerated in this heterogeneous US population, including patients with cirrhosis and hepatic decompensation.
Su1428
Background and aims: Treatment options are limited for patients with HCV infection and advanced fibrosis or cirrhosis before or after liver transplantation. The pangenotypic combination of daclatasvir (DCV) and sofosbuvir (SOF) with ribavirin (RBV) previously demonstrated 94% SVR rates in liver transplant recipients with HCV recurrence, and 83% in patients with advanced cirrhosis. We report interim findings from a US DCV expanded access protocol in patients with decompensated cirrhosis or post-liver transplant recurrence with advanced fibrosis/cirrhosis. Methods: This multi-center, expanded access protocol, provided open-label DCV for use in combination with SOF, ± RBV (at the physician's discretion) for 24 weeks, in patients with genotype (GT) 1-6 in 2 cohorts: (1) decompensated (Child-Pugh C) cirrhosis, and (2) F3 fibrosis, cirrhosis, or fibrosing cholestatic hepatitis after liver transplantation. The HCV TARGET consortium was utilized for treatment and data collection. Results: Of 74 patients treated, 65 received DCV+SOF and 9 DCV+SOF+RBV. Patients were mostly male (80%) and white (88%), with HCV GT 1 (61%) or GT 3 (34%); 43% had failed prior IFN-based regimens, 80% had received a liver transplant, 80% had evidence of prior decompensation, and cirrhosis was present in 84%. At baseline, median (range) platelets were 116 (27-420) x103 cells/uL, albumin 3.3 (1.7-4.7) g/dL, total bilirubin 1.1 (0.3-15.3) mg/dL, and creatinine clearance was 84.8 (35.4-258.7) mL/min. MELD was ‡10 in 59% of patients (24/41) with available scores. Of 41 patients with available data at posttreatment week 12, 35 (85%) achieved SVR. Among the 32 GT 1 patients with available outcomes, 29 achieved SVR (91%), 1 patient relapsed, and 2 were lost to follow-up. Among GT 2 patients, 2 patients achieved SVR and 2 were lost to follow-up. In the 7 GT 3 patients, 6 achieved SVR (86%) and 1 patient had viral breakthrough. Adverse events occurring in ‡10% of patients were fatigue, headache, nausea, diarrhea, abdominal pain, asthenia, insomnia and vomiting. Serious adverse events of interest included hepatic failure (n=1) and renal failure (n=4); 4 patients died (cardiac arrest, hepatic failure, hepatorenal syndrome, sepsis); 10 patients discontinued treatment for adverse events. Conclusion: DCV+SOF±RBV for 24 weeks was efficacious and well-tolerated in patients with decompensated cirrhosis, or severe recurrent post-transplant hepatitis C, receiving this regimen through compassionate use.
Su1427 Improvement in Markers of Liver Fibrosis and Function in HCV Genotype 4Infected Patients With Compensated Cirrhosis Receiving Ombitasvir/ Paritaprevir/Ritonavir With Ribavirin (AGATE-I) Tarek I. Hassanein, Tarik Asselah, Roula B. Qaqish, Christophe Hezode, Jean-Pierre Mulkay, Christophe Moreno, Magdy Elkhashab, Saleh Alqahtani, Yao Yu, Rebecca Redman, Niloufar Mobashery
Su1429
Background and Aims: Patients with chronic hepatitis C virus (HCV) infection and cirrhosis are at higher risk for liver-related complications and historically, more difficult to cure than patients without cirrhosis. The multinational phase 3 AGATE-I trial examined the efficacy and safety of 2 direct-acting antiviral agents (DAA) ombitasvir (OBV), an NS5A inhibitor, and paritaprevir (PTV), an NS3/4A protease inhibitor identified by AbbVie and Enanta, codosed with the ritonavir (r) plus ribavirin (RBV) in patients from North America and Europe with HCV genotype 4 infection and compensated cirrhosis (Hepatology. 2015;62(Suppl 1):563-4A). Here we report trends in key markers of liver fibrosis and function over time in Part 1 of the study. Methods: In Part 1 of AGATE-I, 120 treatment naïve and previous IFN ± RBV experienced patients were randomized 1:1 to receive co-formulated OBV/PTV/ r once daily (25/150/100 mg) with weight-based RBV for 12 weeks (Arm A) or 16 weeks (Arm B). The primary objectives were to assess safety and sustained virologic response (SVR) 12 weeks post treatment (SVR12). Changes in markers of liver fibrosis and function between baseline and post-treatment week 12 are presented here. Results: To date, SVR12 rates in this ongoing study are 96% (52/54) and 100% (49/49), in arms A and B, respectively. Excluding 1 subject with non-virologic failure, the SVR12 rate in Arm A is 98% (52/53). Available mean FibroTest score, ALT, AST, albumin, platelet count, and AFP improved between baseline and post-treatment week 12 (Table). The improvement in each parameter was comparable between the 12- and 16-week treatment duration groups. Complete posttreatment week 12 data will be presented at the meeting for each parameter. Conclusions: In the phase 3 AGATE-I trial, treatment with the 2DAA+RBV regimen for 12 or 16 weeks resulted in an improvement in multiple key liver biomarkers within 12 weeks after completion of antiviral therapy in patients with HCV genotype 4 infection and compensated cirrhosis. Further follow-up of patients will determine the magnitude and durability of these changes.
BACKGROUND: DAA therapies ledipasvir/sofosbuvir (LDV/SOF) and ombitasvir/paritaprevir/ritonavir+dasabuvir (VKP) have yielded SVR12 rates over 95% in clinical trials. Given the remarkable efficacy in clinical trials, understanding factors associated with treatment failure in clinical practice remains challenging due to the relatively few patients who do not achieve an SVR. AIM: The purpose of this study is to examine a large real-world population to assess the characteristics of patients with genotype 1 HCV who failed 12 week LDV/SOF, VKP or other all-oral DAA therapies. METHODS: Data were collected from providers and specialty pharmacies through Trio Health's Innervation Platform, a cloud-based disease management program. All genotype 1 HCV patients who initiated treatment with 12 week LDV/SOF, VKP or simeprevir + sofosbuvir (SMV+SOF)-based regimens between Oct 2014 and June 2015 were included in the analysis (n = 1978). RESULTS SO FAR: Overall SVR12 rate from this heterogeneous population was 94% (1581/1685). By regimen, rates were 94% (1432/1521) for LDV/SOF, 97% (74/76) for LDV/SOF+RBV, 91% (43/47) for VKP+/-RBV and 78% (32/41) for SMV+SOF+/-RBV. Of the 104 patients that did not achieve SVR, 11 discontinued treatment, 39 were lost to follow-up, 3 died, and 51 completed therapy and were virological failures. 9% (149/1685) of patients received a regimen that falls outside of approved FDA labeling, resulting in a 11% decrease in SVR12 rates (84% (125/149) outside approved labeling versus 95% (1456/1685) inside approved labeling). In the virological failures, treatment site (academic versus community practice), age, race, genotype subtype, viral load and presence of HIV coinfection (98% SVR, n = 107) or post-transplant (98% SVR, n = 46) were not associated with treatment failure. Positive association with virological failure in real life was male (76% in failures versus 58% in the full population, p=0.008), cirrhosis (70% in failures versus 31% in the full population, p<0.001), platelets less than 100,000/ml (40% in failures versus 11% in the full population, p<0.001) and receiving a regimen outside of approved FDA labeling (33% in failures versus 10% in the full population, p<0.001). SUMMARY: Overall SVR in real world genotype 1 HCV patients is 94% across regimens and various patient characteristics with cirrhosis and platelets less than 100,000/ ml representing the most difficult to treat patients. 9 % of patients were treated outside of the approved FDA labeling, resulting in an SVR12 rate of 84%. Treatment discontinuation is not a major issue with any all oral DAA therapy.
Failure With All-Oral DAA Regimens: Real-World Experience From the TRIO Network Nezam H. Afdhal, Bruce Bacon, Michael Curry, Douglas Dieterich, Steven Flamm, Lauren Guest, Kris V. Kowdley, Yoori Lee, Naoky Tsai, Zobair M. Younossi
Su1430 Massive Disparity in Insurance Approval for Ledipasvir/Sofosbuvir Based Hepatitis C Therapy For Patients Receiving Medicaid Therapy—A Single Center Experience Mohammad Arsalan Siddiqui, Salwa Hussain, Mostafa Ibrahim, Jeffrey Tang, SyedMohammed Jafri, Hany Eraqi, Omar Sadiq Purpose: We evaluated the success rate for insurance approval for a single center setting for hepatitis C therapy involving ledipasvir/sofosbuvir. Methods: Pharmaceutical records were reviewed for all patients prescribed ledipasvir/sofosbuvir between July 2014 and November 2015. Data was extracted including type of insurance, insurance approval, initiation of therapy, alternate-support path offered and fibrosis staging based on fibroscan or liver biopsy. Results: 783 patients were prescribed therapy with ledipasvir/sofosbuvir based therapy. The
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AASLD Abstracts
Daclatasvir and Sofosbuvir Therapy for Patients with Decompensated Cirrhosis or Post-Liver Transplant HCV Recurrence and Advanced Fibrosis or Cirrhosis: United States Multicenter Treatment Protocol Robert S. Brown, Michael Fried, K R. Reddy, Consuelo Soldevila-Pico, Saro Khemichian, Jama Darling, Andrew A. Napoli, Beatrice Anduze-Faris, Paul Y. Kwo
Su1428
Background and aims: Treatment options are limited for patients with HCV infection and advanced fibrosis or cirrhosis before or after liver transplantation. The pangenotypic combination of daclatasvir (DCV) and sofosbuvir (SOF) with ribavirin (RBV) previously demonstrated 94% SVR rates in liver transplant recipients with HCV recurrence, and 83% in patients with advanced cirrhosis. We report interim findings from a US DCV expanded access protocol in patients with decompensated cirrhosis or post-liver transplant recurrence with advanced fibrosis/cirrhosis. Methods: This multi-center, expanded access protocol, provided open-label DCV for use in combination with SOF, ± RBV (at the physician's discretion) for 24 weeks, in patients with genotype (GT) 1-6 in 2 cohorts: (1) decompensated (Child-Pugh C) cirrhosis, and (2) F3 fibrosis, cirrhosis, or fibrosing cholestatic hepatitis after liver transplantation. The HCV TARGET consortium was utilized for treatment and data collection. Results: Of 74 patients treated, 65 received DCV+SOF and 9 DCV+SOF+RBV. Patients were mostly male (80%) and white (88%), with HCV GT 1 (61%) or GT 3 (34%); 43% had failed prior IFN-based regimens, 80% had received a liver transplant, 80% had evidence of prior decompensation, and cirrhosis was present in 84%. At baseline, median (range) platelets were 116 (27-420) x103 cells/uL, albumin 3.3 (1.7-4.7) g/dL, total bilirubin 1.1 (0.3-15.3) mg/dL, and creatinine clearance was 84.8 (35.4-258.7) mL/min. MELD was ‡10 in 59% of patients (24/41) with available scores. Of 41 patients with available data at posttreatment week 12, 35 (85%) achieved SVR. Among the 32 GT 1 patients with available outcomes, 29 achieved SVR (91%), 1 patient relapsed, and 2 were lost to follow-up. Among GT 2 patients, 2 patients achieved SVR and 2 were lost to follow-up. In the 7 GT 3 patients, 6 achieved SVR (86%) and 1 patient had viral breakthrough. Adverse events occurring in ‡10% of patients were fatigue, headache, nausea, diarrhea, abdominal pain, asthenia, insomnia and vomiting. Serious adverse events of interest included hepatic failure (n=1) and renal failure (n=4); 4 patients died (cardiac arrest, hepatic failure, hepatorenal syndrome, sepsis); 10 patients discontinued treatment for adverse events. Conclusion: DCV+SOF±RBV for 24 weeks was efficacious and well-tolerated in patients with decompensated cirrhosis, or severe recurrent post-transplant hepatitis C, receiving this regimen through compassionate use.
Su1427 Improvement in Markers of Liver Fibrosis and Function in HCV Genotype 4Infected Patients With Compensated Cirrhosis Receiving Ombitasvir/ Paritaprevir/Ritonavir With Ribavirin (AGATE-I) Tarek I. Hassanein, Tarik Asselah, Roula B. Qaqish, Christophe Hezode, Jean-Pierre Mulkay, Christophe Moreno, Magdy Elkhashab, Saleh Alqahtani, Yao Yu, Rebecca Redman, Niloufar Mobashery
Su1429
Background and Aims: Patients with chronic hepatitis C virus (HCV) infection and cirrhosis are at higher risk for liver-related complications and historically, more difficult to cure than patients without cirrhosis. The multinational phase 3 AGATE-I trial examined the efficacy and safety of 2 direct-acting antiviral agents (DAA) ombitasvir (OBV), an NS5A inhibitor, and paritaprevir (PTV), an NS3/4A protease inhibitor identified by AbbVie and Enanta, codosed with the ritonavir (r) plus ribavirin (RBV) in patients from North America and Europe with HCV genotype 4 infection and compensated cirrhosis (Hepatology. 2015;62(Suppl 1):563-4A). Here we report trends in key markers of liver fibrosis and function over time in Part 1 of the study. Methods: In Part 1 of AGATE-I, 120 treatment naïve and previous IFN ± RBV experienced patients were randomized 1:1 to receive co-formulated OBV/PTV/ r once daily (25/150/100 mg) with weight-based RBV for 12 weeks (Arm A) or 16 weeks (Arm B). The primary objectives were to assess safety and sustained virologic response (SVR) 12 weeks post treatment (SVR12). Changes in markers of liver fibrosis and function between baseline and post-treatment week 12 are presented here. Results: To date, SVR12 rates in this ongoing study are 96% (52/54) and 100% (49/49), in arms A and B, respectively. Excluding 1 subject with non-virologic failure, the SVR12 rate in Arm A is 98% (52/53). Available mean FibroTest score, ALT, AST, albumin, platelet count, and AFP improved between baseline and post-treatment week 12 (Table). The improvement in each parameter was comparable between the 12- and 16-week treatment duration groups. Complete posttreatment week 12 data will be presented at the meeting for each parameter. Conclusions: In the phase 3 AGATE-I trial, treatment with the 2DAA+RBV regimen for 12 or 16 weeks resulted in an improvement in multiple key liver biomarkers within 12 weeks after completion of antiviral therapy in patients with HCV genotype 4 infection and compensated cirrhosis. Further follow-up of patients will determine the magnitude and durability of these changes.
BACKGROUND: DAA therapies ledipasvir/sofosbuvir (LDV/SOF) and ombitasvir/paritaprevir/ritonavir+dasabuvir (VKP) have yielded SVR12 rates over 95% in clinical trials. Given the remarkable efficacy in clinical trials, understanding factors associated with treatment failure in clinical practice remains challenging due to the relatively few patients who do not achieve an SVR. AIM: The purpose of this study is to examine a large real-world population to assess the characteristics of patients with genotype 1 HCV who failed 12 week LDV/SOF, VKP or other all-oral DAA therapies. METHODS: Data were collected from providers and specialty pharmacies through Trio Health's Innervation Platform, a cloud-based disease management program. All genotype 1 HCV patients who initiated treatment with 12 week LDV/SOF, VKP or simeprevir + sofosbuvir (SMV+SOF)-based regimens between Oct 2014 and June 2015 were included in the analysis (n = 1978). RESULTS SO FAR: Overall SVR12 rate from this heterogeneous population was 94% (1581/1685). By regimen, rates were 94% (1432/1521) for LDV/SOF, 97% (74/76) for LDV/SOF+RBV, 91% (43/47) for VKP+/-RBV and 78% (32/41) for SMV+SOF+/-RBV. Of the 104 patients that did not achieve SVR, 11 discontinued treatment, 39 were lost to follow-up, 3 died, and 51 completed therapy and were virological failures. 9% (149/1685) of patients received a regimen that falls outside of approved FDA labeling, resulting in a 11% decrease in SVR12 rates (84% (125/149) outside approved labeling versus 95% (1456/1685) inside approved labeling). In the virological failures, treatment site (academic versus community practice), age, race, genotype subtype, viral load and presence of HIV coinfection (98% SVR, n = 107) or post-transplant (98% SVR, n = 46) were not associated with treatment failure. Positive association with virological failure in real life was male (76% in failures versus 58% in the full population, p=0.008), cirrhosis (70% in failures versus 31% in the full population, p<0.001), platelets less than 100,000/ml (40% in failures versus 11% in the full population, p<0.001) and receiving a regimen outside of approved FDA labeling (33% in failures versus 10% in the full population, p<0.001). SUMMARY: Overall SVR in real world genotype 1 HCV patients is 94% across regimens and various patient characteristics with cirrhosis and platelets less than 100,000/ ml representing the most difficult to treat patients. 9 % of patients were treated outside of the approved FDA labeling, resulting in an SVR12 rate of 84%. Treatment discontinuation is not a major issue with any all oral DAA therapy.
Failure With All-Oral DAA Regimens: Real-World Experience From the TRIO Network Nezam H. Afdhal, Bruce Bacon, Michael Curry, Douglas Dieterich, Steven Flamm, Lauren Guest, Kris V. Kowdley, Yoori Lee, Naoky Tsai, Zobair M. Younossi
Su1430 Massive Disparity in Insurance Approval for Ledipasvir/Sofosbuvir Based Hepatitis C Therapy For Patients Receiving Medicaid Therapy—A Single Center Experience Mohammad Arsalan Siddiqui, Salwa Hussain, Mostafa Ibrahim, Jeffrey Tang, SyedMohammed Jafri, Hany Eraqi, Omar Sadiq Purpose: We evaluated the success rate for insurance approval for a single center setting for hepatitis C therapy involving ledipasvir/sofosbuvir. Methods: Pharmaceutical records were reviewed for all patients prescribed ledipasvir/sofosbuvir between July 2014 and November 2015. Data was extracted including type of insurance, insurance approval, initiation of therapy, alternate-support path offered and fibrosis staging based on fibroscan or liver biopsy. Results: 783 patients were prescribed therapy with ledipasvir/sofosbuvir based therapy. The
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AASLD Abstracts
Daclatasvir and Sofosbuvir Therapy for Patients with Decompensated Cirrhosis or Post-Liver Transplant HCV Recurrence and Advanced Fibrosis or Cirrhosis: United States Multicenter Treatment Protocol Robert S. Brown, Michael Fried, K R. Reddy, Consuelo Soldevila-Pico, Saro Khemichian, Jama Darling, Andrew A. Napoli, Beatrice Anduze-Faris, Paul Y. Kwo