- Email: [email protected]
Ledipasvir Without Ribavirin in Patients With HCV Recurrence After Liver Transplantation
over-all approval rate was 77.8% (609 patients). 144 patient (18.3%) were declined ledipasvir/ sofosbuvir by insurance companies of whom 68 patients were offered support path for alternate therapy with ombitasvir/paritaprevir/ritonavir with dasabuvir. Rest of the 30 patients (3.8%) were still pending approval. 296 patients (37.8%) had Medicare, 424 (54.1%) private insurance and (8.2%) had Medicaid. The approval rates were 89% for Medicare patients, 71% for private insurances and 30% for Medicaid patients. Amongst private insurances, Private A had approval rate of 71%, Private B had approval rate of 76% and other private insurances had approval of 61%. The approval rates by fibrosis stage 1-4 were 72%, 79%, 80% and 87% respectively. Table 1 reflects approval by fibrosis stage and insurance type. Table 2 reflects approval rates by fibrosis stage. Conclusion: We evaluated insurance approval for ledipasvir/sofosbuvir based hepatitis C therapy. The over-all approval rate of therapy based on ledipasvir/sofosbuvir was 77.8% with Medicare having the highest approval rate at 89%. Medicaid patients had a very low approval rate at 30%. Approval rates for Medicaid were lower across all stages of fibrosis. The overall approval rates were associated with fibrosis staging with stage 1 having the lowest approval rate of 72% and stage 4 at 87%. Table 1. Approval rates by fibrosis stages based on insurance type.
(SVR12). Secondary outcomes included virologic failure on treatment, relapse after treatment, and side effects. Results: Thirty-six patients (8F, 28M) with a mean age 61.1 ± 8.1 years, mean duration from LT of 56.4 months (range of 6-156 months), and mean baseline viral load of 6.84 million IU/mL were treated. Twenty-seven patients were treated for 12 weeks and 9 patients were treated for 24 weeks (6 with cirrhosis of the allograft and 3 with fibrosing cholestatic hepatitis). Twenty were HCV treatment naïve and sixteen were treatment experienced. SVR12 data were available in 19 patients at the time of abstract submission and 19/19 achieved SVR12 (100%). No virologic failures or relapses were observed. There was no significant change in hemoglobin level between baseline and the end of treatment (12.6 g/dL and 13.5 g/dL, respectively). The most common side effects were fatigue, insomnia and headaches but no serious adverse events were reported during treatment. Full SVR12 data will be presented at the meeting. Conclusion: The combination of sofosbuvir/ ledipasvir without ribavirin for 12 or 24 weeks produced high rates of SVR12 in patients with HCV recurrence after liver transplantation. The use of ribavirin may not be necessary to achieve SVR12 in this patient population.
Su1433 Real World Experience in Treating Non-Cirrhotic Patients With Genotype 1 Chronic Hepatitis C using Paritaprevir/Ritonavir, Ombitasvir, and Dasabuvir With or Without Ribavirin. A prospective Study in a Large Community Based United States Health Care Delivery System Lisa M. Nyberg, Robert A. Rathbun, Henry K. Niho, Lien Nguyen, Heather Patton, Amandeep K. Sahota, William J. Towner, Anders H. Nyberg
AASLD Abstracts
Table 2. Overall approval rates by fibrosis stage
Phase 3 registration trials evaluating the safety and efficacy of Paritaprevir/ritonavir, Ombitasvir, and Dasabuvir (PrOD) +/- ribavirin (RBV) have shown high efficacy and excellent tolerability. However, when new treatment regimens are widely used in "The Real World", the safety and efficacy may not be as good as that seen in clinical trials. The aim of this study was to evaluate the safety and efficacy of PrOD in a prospective study in a real world setting, Kaiser Permanente Southern California (KPSC), a large U.S. based Health Care Delivery System. Methods: The study was conducted at four sites at KPSC in Southern California. N=200 patients will be included in two phases. Inclusion criteria: Chronic hepatitis C, genotype 1 (GT1), age ‡ 18, treatment-naive (TN) or treatment experienced (TE) with interferon-based therapy. Exclusion criteria were non-GT1 chronic hepatitis C, coinfection with HIV or HBV, prior treatment with direct-acting antiviral agent(s), glomerular filtration rate < 30 mL/minute, hemoglobin <12 for males and <11 for females, and/or evidence of cirrhosis and/or hepatocellular carcinoma. Cirrhosis was defined as Metavir score > 3 or Ishak score >4 on liver biopsy, Fibroscan score >12.5 kPa, APRI score of >1.5, clinical evidence of cirrhosis and/or history of hepatic decompensation. Genotype 1a (GT1a) patients were treated with PrOD + weight-based RBV x 12 weeks and Genotype 1b (GT1b) patients were treated with PrOD x 12 weeks. Results: This is an analysis of Phase 1 including an N of 100, 60% male, 61% GT1a, 39% GT1b, mean age 58, 89% white or hispanic, mean BMI: 25.4, 79% TE and 90% had baseline HCV RNA > 800,000 IU/mL. 99% had undetected HCV RNA at end treatment (one patient withdrew consent). To date, 71 patients have reached post-treatment week 4 (PTW 4) and 66/71 (93%) have undetected HCV RNA at PTW 4 (SVR4). 3 patients relapsed between end treatment and PTW 4. Resistance testing by next generation sequencing performed on one patient detected mutations at M28V and Q30R. The treatment was well tolerated overall with expected reduction in hemoglobin in those on ribavirin. One patient stopped treatment at week 11 due to acute pancreatitis felt to possibly be related to study drug. The patient achieved SVR4. Another adverse event felt to possibly be drug related was Guillain Barre syndrome diagnosed 3 days after end treatment. A third adverse event was not considered drug related: bladder cancer diagnosed in a patient with a history of hematuria. Conclusions: In this prospective study conducted in a "Real World" care delivery setting, treatment of genotype 1 chronic hepatitis C with Paritaprevir/ ritonavir, Ombitasvir, and Dasabuvir (PrOD) +/- ribavirin was well tolerated and highly effective. To date, sustained virological response rates have been comparable to that seen in the registration trials. Further analysis is ongoing.
Su1431 Use of 8 Weeks Regimen of Sofosbuvir And Ledipasvir Without Ribavirin, In Non-Cirrhotic Treatment-Naïve Hepatitis C Genotype 1 Patients With Less Than 6 Million IU/ml Viral Load: Real-World Experience Kamran Qureshi, John Regester, Joshua Halladay, Paul Urick Background and Aims: In clinical trials including patients with Hepatitis C viral (HCV) genotype 1 infection the 8 weeks fixed dose regimen of Sofosbuvir and Ledipasvir (Sof/Led) as 150mg/90mg combination without ribavirin showed have high rates of sustained virologic response (SVR12). SVR12 rates were particularly high in those without prior treatment experience, and with baseline HCV viral load of less than 6 million IU/mL. General use of this regimen in clinical practice, however, was advised with caution because of unclear reliability of methods of diagnosis of cirrhosis, and fluctuating nature of viral loads in reallife experience. The 8 weeks regimen is favoured in real-world because shorter duration and lower costs to the payers. The aim of this study is to determine practive patterns, ease of treatment and follow up of this short and effective regimen for treatment of HCV genotype 1 infection in selected population. Methods: We used pharmacy data, and included all patients who were provided 8 weeks Sof/Led by Burmans Specialty Pharmacy, among other approved regimens and evaluated the choice of this regimen among various HCV medication prescribers. Burmans Specialty Pharmacy works with multiple prescribers and institutions, and serves a large population residing in PA, NJ, DE, and MD states in North Eastern region of United States. We collected data of clinical outcomes from the pharmacy database and evaluated for any specific side effects in the patients treated at our institution. Results: Out of 2580 HCV patients who were treated with various Sof/Led based regimens from Nov 2014 till July 2015, 350 patients took 8 weeks regimen of Sof/Led. SVR12 data was available for 206, which were included in analysis and were all treatment naïve HCV genotype 1 (1a: 74.2%, 1b: 24.2%, 1a/1b:1.5%) patients. Median (range) age was 57 (23-80) years, 50.1% were males while 59.7% were Caucasians, followed by 24.2% African Americans. Fibrosis stage was reported as F0 and F1 in 17.4% each, F2 in 27.1%, F3 in 16.9% and "noncirrhotic" in 20.8%. Median (range) baseline HCV viral load was 1.3 million (493 - 5.6 million) IU/mL. SVR12 was achieved in 201 of 206 patients (97.5%). All 5 patients who relapsed after therapy completion, were African Americans (3 males, 2 females), 4 had F3 fibrosis and 1 was reported as "non-cirrhotic", 3 had genotype 1a, 1 had 1b, and 1 had 1a/ 1b. The SVR12 rates were low (88.5%) with F3, in particular in African American with F3 (12/16: 75%). There were no drug discontinuations and no severe adverse effects were reported. 80% of patients were treated by gastroenterologists Conclusions: 8 weeks therapy of Sof/Led in HCV genotype 1 seems to be effective and is well-tolerated in clinical practice. Use of this approach in African Americans with evidence of advanced fibrosis needs discretion, and further review of accumulating data.
Su1434 DAA Therapy Results in High SVR Rates Among Immunosuppressed Patients With Chronic Hepatitis C on Chemotherapy Priya K. Simoes, Jaclyn Newfield, Maya Gambarin-Gelwan INTRODUCTION: Acute exacerbation of hepatitis C (HCV) can occur in about 11 % of patients with chronic infection undergoing chemotherapy, especially those with hematological malignancies or on Rituximab. This can lead to worsening hepatic function, particularly in those with cirrhosis, as well as discontinuation of chemotherapy and negatively impact oncologic outcomes. Treatment of chronic hepatitis C (CHC) prior to or during chemotherapy may decrease the risk of exacerbation of HCV and hepatic decompensation, allow for successful completion of chemotherapy and improve oncologic outcomes. Data on the efficacy of direct acting antiviral agents (DAAs) in this population is limited. AIM: To assess sustained virologic response (SVR) rates in patients undergoing treatment for CHC with DAAs while immunosuppressed due to chemotherapy. METHODS: All patients who completed DAA therapy for CHC between February 2014 and November 2015 while on or within 6 months of receiving chemotherapy were included. Data was obtained from the electronic medical record. RESULTS: Eleven patients fitting our inclusion criteria were identified; all were males. 72% had HCV-genotype 1(G1a 5/8 patients), 64 % were treatmentexperienced and 82% had F3/F4 fibrosis. Four out of eight cirrhotic patients were ChildPugh B (Table). All patients completed planned anti-viral therapy (AVT), except for patient #6 due to lack of insurance coverage. There were no serious adverse events related to DAAs. SVR-4 was achieved in 82% (9/11) patients. Patient #8 with HCV-G3 cirrhosis had persistent low level viremia throughout treatment with SOF+RBV; AVT was continued in order to allow him to complete chemotherapy. Patient # 4 with Child-Pugh B cirrhosis (with hepatic decompensation on rituximab-bendamustine-cytarabine pre-AVT), relapsed after 48 weeks of SOF+RBV, however he was able to complete further chemotherapy without liver-related interruptions. Eight patients had 12-week post-treatment HCV PCR available; 75% achieved SVR-12 (data on the remaining 2 will be available by DDW). There were no interruptions
Su1432 High Efficacy of Sofosbuvir/ Ledipasvir Without Ribavirin in Patients With HCV Recurrence After Liver Transplantation Mohamed A. Elfeki, Rachel Abou Mrad, Jamak Modaresi Esfeh, Nizar N. Zein, Bijan Eghtesad, Ibrahim A. Hanouneh, Naim Alkhouri Background: Currently recommended regimens to treat patients with HCV infection in the allograft include the use of ribavirin. Limited data are available on ribavirin-free regimens after liver transplantation (LT). The aim of this study was to assess the efficacy of sofosbuvir/ ledipasvir fixed-dose combination without ribavirin in patients with HCV recurrence postLT. Methods: Patients with HCV recurrence post-LT were included in this study. The combination of sofosbuvir (400 mg daily) + ledipasvir (90 mg daily) was used for 12 weeks in patients without cirrhosis of the allograft and for 24 weeks in patients with allograft cirrhosis or fibrosing cholestatic hepatitis regardless of prior treatment experience. The primary end point was sustained virologic response at 12 weeks after the end of treatment
AASLD Abstracts
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(SVR12). Secondary outcomes included virologic failure on treatment, relapse after treatment, and side effects. Results: Thirty-six patients (8F, 28M) with a mean age 61.1 ± 8.1 years, mean duration from LT of 56.4 months (range of 6-156 months), and mean baseline viral load of 6.84 million IU/mL were treated. Twenty-seven patients were treated for 12 weeks and 9 patients were treated for 24 weeks (6 with cirrhosis of the allograft and 3 with fibrosing cholestatic hepatitis). Twenty were HCV treatment naïve and sixteen were treatment experienced. SVR12 data were available in 19 patients at the time of abstract submission and 19/19 achieved SVR12 (100%). No virologic failures or relapses were observed. There was no significant change in hemoglobin level between baseline and the end of treatment (12.6 g/dL and 13.5 g/dL, respectively). The most common side effects were fatigue, insomnia and headaches but no serious adverse events were reported during treatment. Full SVR12 data will be presented at the meeting. Conclusion: The combination of sofosbuvir/ ledipasvir without ribavirin for 12 or 24 weeks produced high rates of SVR12 in patients with HCV recurrence after liver transplantation. The use of ribavirin may not be necessary to achieve SVR12 in this patient population.
Su1433 Real World Experience in Treating Non-Cirrhotic Patients With Genotype 1 Chronic Hepatitis C using Paritaprevir/Ritonavir, Ombitasvir, and Dasabuvir With or Without Ribavirin. A prospective Study in a Large Community Based United States Health Care Delivery System Lisa M. Nyberg, Robert A. Rathbun, Henry K. Niho, Lien Nguyen, Heather Patton, Amandeep K. Sahota, William J. Towner, Anders H. Nyberg
AASLD Abstracts
Table 2. Overall approval rates by fibrosis stage
Phase 3 registration trials evaluating the safety and efficacy of Paritaprevir/ritonavir, Ombitasvir, and Dasabuvir (PrOD) +/- ribavirin (RBV) have shown high efficacy and excellent tolerability. However, when new treatment regimens are widely used in "The Real World", the safety and efficacy may not be as good as that seen in clinical trials. The aim of this study was to evaluate the safety and efficacy of PrOD in a prospective study in a real world setting, Kaiser Permanente Southern California (KPSC), a large U.S. based Health Care Delivery System. Methods: The study was conducted at four sites at KPSC in Southern California. N=200 patients will be included in two phases. Inclusion criteria: Chronic hepatitis C, genotype 1 (GT1), age ‡ 18, treatment-naive (TN) or treatment experienced (TE) with interferon-based therapy. Exclusion criteria were non-GT1 chronic hepatitis C, coinfection with HIV or HBV, prior treatment with direct-acting antiviral agent(s), glomerular filtration rate < 30 mL/minute, hemoglobin <12 for males and <11 for females, and/or evidence of cirrhosis and/or hepatocellular carcinoma. Cirrhosis was defined as Metavir score > 3 or Ishak score >4 on liver biopsy, Fibroscan score >12.5 kPa, APRI score of >1.5, clinical evidence of cirrhosis and/or history of hepatic decompensation. Genotype 1a (GT1a) patients were treated with PrOD + weight-based RBV x 12 weeks and Genotype 1b (GT1b) patients were treated with PrOD x 12 weeks. Results: This is an analysis of Phase 1 including an N of 100, 60% male, 61% GT1a, 39% GT1b, mean age 58, 89% white or hispanic, mean BMI: 25.4, 79% TE and 90% had baseline HCV RNA > 800,000 IU/mL. 99% had undetected HCV RNA at end treatment (one patient withdrew consent). To date, 71 patients have reached post-treatment week 4 (PTW 4) and 66/71 (93%) have undetected HCV RNA at PTW 4 (SVR4). 3 patients relapsed between end treatment and PTW 4. Resistance testing by next generation sequencing performed on one patient detected mutations at M28V and Q30R. The treatment was well tolerated overall with expected reduction in hemoglobin in those on ribavirin. One patient stopped treatment at week 11 due to acute pancreatitis felt to possibly be related to study drug. The patient achieved SVR4. Another adverse event felt to possibly be drug related was Guillain Barre syndrome diagnosed 3 days after end treatment. A third adverse event was not considered drug related: bladder cancer diagnosed in a patient with a history of hematuria. Conclusions: In this prospective study conducted in a "Real World" care delivery setting, treatment of genotype 1 chronic hepatitis C with Paritaprevir/ ritonavir, Ombitasvir, and Dasabuvir (PrOD) +/- ribavirin was well tolerated and highly effective. To date, sustained virological response rates have been comparable to that seen in the registration trials. Further analysis is ongoing.
Su1431 Use of 8 Weeks Regimen of Sofosbuvir And Ledipasvir Without Ribavirin, In Non-Cirrhotic Treatment-Naïve Hepatitis C Genotype 1 Patients With Less Than 6 Million IU/ml Viral Load: Real-World Experience Kamran Qureshi, John Regester, Joshua Halladay, Paul Urick Background and Aims: In clinical trials including patients with Hepatitis C viral (HCV) genotype 1 infection the 8 weeks fixed dose regimen of Sofosbuvir and Ledipasvir (Sof/Led) as 150mg/90mg combination without ribavirin showed have high rates of sustained virologic response (SVR12). SVR12 rates were particularly high in those without prior treatment experience, and with baseline HCV viral load of less than 6 million IU/mL. General use of this regimen in clinical practice, however, was advised with caution because of unclear reliability of methods of diagnosis of cirrhosis, and fluctuating nature of viral loads in reallife experience. The 8 weeks regimen is favoured in real-world because shorter duration and lower costs to the payers. The aim of this study is to determine practive patterns, ease of treatment and follow up of this short and effective regimen for treatment of HCV genotype 1 infection in selected population. Methods: We used pharmacy data, and included all patients who were provided 8 weeks Sof/Led by Burmans Specialty Pharmacy, among other approved regimens and evaluated the choice of this regimen among various HCV medication prescribers. Burmans Specialty Pharmacy works with multiple prescribers and institutions, and serves a large population residing in PA, NJ, DE, and MD states in North Eastern region of United States. We collected data of clinical outcomes from the pharmacy database and evaluated for any specific side effects in the patients treated at our institution. Results: Out of 2580 HCV patients who were treated with various Sof/Led based regimens from Nov 2014 till July 2015, 350 patients took 8 weeks regimen of Sof/Led. SVR12 data was available for 206, which were included in analysis and were all treatment naïve HCV genotype 1 (1a: 74.2%, 1b: 24.2%, 1a/1b:1.5%) patients. Median (range) age was 57 (23-80) years, 50.1% were males while 59.7% were Caucasians, followed by 24.2% African Americans. Fibrosis stage was reported as F0 and F1 in 17.4% each, F2 in 27.1%, F3 in 16.9% and "noncirrhotic" in 20.8%. Median (range) baseline HCV viral load was 1.3 million (493 - 5.6 million) IU/mL. SVR12 was achieved in 201 of 206 patients (97.5%). All 5 patients who relapsed after therapy completion, were African Americans (3 males, 2 females), 4 had F3 fibrosis and 1 was reported as "non-cirrhotic", 3 had genotype 1a, 1 had 1b, and 1 had 1a/ 1b. The SVR12 rates were low (88.5%) with F3, in particular in African American with F3 (12/16: 75%). There were no drug discontinuations and no severe adverse effects were reported. 80% of patients were treated by gastroenterologists Conclusions: 8 weeks therapy of Sof/Led in HCV genotype 1 seems to be effective and is well-tolerated in clinical practice. Use of this approach in African Americans with evidence of advanced fibrosis needs discretion, and further review of accumulating data.
Su1434 DAA Therapy Results in High SVR Rates Among Immunosuppressed Patients With Chronic Hepatitis C on Chemotherapy Priya K. Simoes, Jaclyn Newfield, Maya Gambarin-Gelwan INTRODUCTION: Acute exacerbation of hepatitis C (HCV) can occur in about 11 % of patients with chronic infection undergoing chemotherapy, especially those with hematological malignancies or on Rituximab. This can lead to worsening hepatic function, particularly in those with cirrhosis, as well as discontinuation of chemotherapy and negatively impact oncologic outcomes. Treatment of chronic hepatitis C (CHC) prior to or during chemotherapy may decrease the risk of exacerbation of HCV and hepatic decompensation, allow for successful completion of chemotherapy and improve oncologic outcomes. Data on the efficacy of direct acting antiviral agents (DAAs) in this population is limited. AIM: To assess sustained virologic response (SVR) rates in patients undergoing treatment for CHC with DAAs while immunosuppressed due to chemotherapy. METHODS: All patients who completed DAA therapy for CHC between February 2014 and November 2015 while on or within 6 months of receiving chemotherapy were included. Data was obtained from the electronic medical record. RESULTS: Eleven patients fitting our inclusion criteria were identified; all were males. 72% had HCV-genotype 1(G1a 5/8 patients), 64 % were treatmentexperienced and 82% had F3/F4 fibrosis. Four out of eight cirrhotic patients were ChildPugh B (Table). All patients completed planned anti-viral therapy (AVT), except for patient #6 due to lack of insurance coverage. There were no serious adverse events related to DAAs. SVR-4 was achieved in 82% (9/11) patients. Patient #8 with HCV-G3 cirrhosis had persistent low level viremia throughout treatment with SOF+RBV; AVT was continued in order to allow him to complete chemotherapy. Patient # 4 with Child-Pugh B cirrhosis (with hepatic decompensation on rituximab-bendamustine-cytarabine pre-AVT), relapsed after 48 weeks of SOF+RBV, however he was able to complete further chemotherapy without liver-related interruptions. Eight patients had 12-week post-treatment HCV PCR available; 75% achieved SVR-12 (data on the remaining 2 will be available by DDW). There were no interruptions
Su1432 High Efficacy of Sofosbuvir/ Ledipasvir Without Ribavirin in Patients With HCV Recurrence After Liver Transplantation Mohamed A. Elfeki, Rachel Abou Mrad, Jamak Modaresi Esfeh, Nizar N. Zein, Bijan Eghtesad, Ibrahim A. Hanouneh, Naim Alkhouri Background: Currently recommended regimens to treat patients with HCV infection in the allograft include the use of ribavirin. Limited data are available on ribavirin-free regimens after liver transplantation (LT). The aim of this study was to assess the efficacy of sofosbuvir/ ledipasvir fixed-dose combination without ribavirin in patients with HCV recurrence postLT. Methods: Patients with HCV recurrence post-LT were included in this study. The combination of sofosbuvir (400 mg daily) + ledipasvir (90 mg daily) was used for 12 weeks in patients without cirrhosis of the allograft and for 24 weeks in patients with allograft cirrhosis or fibrosing cholestatic hepatitis regardless of prior treatment experience. The primary end point was sustained virologic response at 12 weeks after the end of treatment
AASLD Abstracts
S-1098
X : 10052$CH02 03-28-16 22:36:37
Page 1098