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Sofosbuvir Treatment for 8 Weeks in Treatment-Naïve HCV Genotype 1 Infected Patients under Real Life Conditions: Data from the German Hepatitis C-Registry (DHC-R)
POSTER PRESENTATIONS the cost per SVR is significantly lower in naïve and NC when compared to TE and cirrhotic patients, indicating an economic benefit of early treatment and the selection of highly effective and well tolerated therapies. SAT-241 LEDIPASVIR/SOFOSBUVIR TREATMENT FOR 8 WEEKS IN TREATMENT-NAÏVE HCV GENOTYPE 1 INFECTED PATIENTS UNDER REAL LIFE CONDITIONS: DATA FROM THE GERMAN HEPATITIS C-REGISTRY (DHC-R) P. Buggisch1, K.H.W. Böker2, R. Günther3, G. Teuber4, H. Klinker5, A. Pathil6, S. Christensen7, H. Peiffer-Vornkahl8, K.-G. Simon9, C. Niederau10, H. Wedemeyer11, S. Zeuzem12, German Hepatitis C-Registry13. 1IFI-Institute for Interdisciplinary Medicine, Hamburg; 2 Hepatologische Praxis, Hannover; 3Universitätsklinikum SchleswigHolstein (UKSH), Campus Kiel, Kiel; 4Hepatologische Praxis, Frankfurt; 5 University Hospital Würzburg, Würzburg; 6University Hospital Heidelberg, Heidelberg; 7CIM Münster, Münster; 8e.factum GmbH, Butzbach; 9Hepatologische Praxis, Leverkusen; 10Hospital Oberhausen, Oberhausen; 11Hannover Medical School, Hannover; 12J.W. Goethe University Frankfurt, Frankfurt; 13Leberstiftungs-GmbH Deutschland, Hannover, Germany E-mail: [email protected] Background and Aims: Ledipasvir/Sofosbuvir (LDV/SOF) for 8–24 weeks is approved for the treatment of chronic hepatitis C. In the ION3 study 8 weeks of LDV/SOF was non-inferior to 12 wks in previously untreated GT1 patients without cirrhosis. According to the summary of product characteristics (SmPC) a treatment duration of 8 wks may be considered in naïve non-cirrhotic HCV GT1 infected patients with viral load <6 Mio IU/mL. Aim of this analysis was to evaluate the virologic response rates of 8 wks treatment under real world conditions. Methods: The DHC-R (Deutsches Hepatitis C-Register) is a registry for the documentation of the HCV treatment situation in Germany. Data are collected in a centralized database and on-site monitoring is implemented. Data collection is ongoing. In this analysis data of patients with 8 or 12 wks treatment with LDV/SOF and available SVR12 data (until 9/2015) were included. Baseline characteristics, prior treatment history, safety and effectiveness were investigated. Results: 262 (141 female) pts (8 week) and 444 (210 female) pts (12 week) met the inclusion criteria. One pt in the 8 week group (1) and 130 in the 12 week group (2) had weight-based ribavirin added to LDV/SOF. The mean (SD) age was 50.4 (13.1) yrs in group 1, 55.0 (12.6) in group 2. Genotype distribution was 98.1% for GT1 and 1.9% GT4. In 37% the fibrosis stage was evaluated by elastography (Fibroscan), the mean (SD) stiffness value in group 1 was 6.2 kPa (2.4) and 10.4 kPa (8.1) in group 2. One pt in group 1 had a liver stiffness ≥16.5 kPa, 8 were categorized as cirrhotic (2 relapses). Mean HCV RNA at baseline was 1,606,548 IU/mL (3,375,284) in group 1 and 2,727,867 IU/mL (6,227,207) in group 2. Seven pts of group 1 had a baseline viral load >6 Mio IU/mL (1 relapse). 17 pts in group 1 were HIV co-infected, 24 pts received substitution treatment. 24 pts in group 1 had prior treatment. SVR12 (ITT) in group 1 was 88.5% (232/262) (13 relapses documented, SVR12 not determined in 17) and 92.6% (2.5% not determined) in group 2. Three out of the yet documented 20 relapses occurred in pts treated outside the selection criteria. In the per protocol analysis the SVR12 rates were 95.5% and 95.1% in group 1 and 2, respectively. Conclusions: Under real world conditions, 8 wks LDV/SOF achieves comparable SVR rates to 12 weeks treatment, but relapses are more frequent in particular in patients who do not meet the selection criteria according to the SmPC.
S810
SAT-242 LEDIPASVIR/SOFOSBUVIR (LDV/SOF) FOR 8 WKS IN GENOTYPE 1 (GT1) TREATMENT-NAÏVE NON-CIRRHOTIC PATIENTS WITH HCV VIRAL LOAD <6 MILLION IU/ML (6M); A COMPARATIVE ANALYSIS OF THE PHASE-3 ION-3 DATA TO REAL WORLD EFFECTIVENESS P. Buggisch1, J. Peterson1, S. Mauss2, K. Kowdley3, M. Curry4, P. Ruane5, D. Ain5, N. Tsai6, Y. Lee7, E. Eggleton8, M. Natha9, B. Kreter9, D. Brainard 9, P. Ingiliz10. 1IFI Institut für Interdisziplinäre Medizin, Asklepios Klinik St. Georg, Hamburg; 2Center for HIV and Hepatogastroenterology, Duesseldorf, Germany; 3Swedish Medical Center, Seattle; 4Beth Israel, Boston; 5Ruane Medical and Liver Health Institute, Los Angeles; 6Queens Medical Center, Honolulu; 7TRIO Health Analytics, Newton; 8Gilead Sciences, Los Angeles; 9Gilead Sciences, Foster City, United States; 10Medizinisches Infektiologie Zentrum, Berlin, Germany E-mail: [email protected] Background and Aims: The optimal duration of therapy to achieve SVR depends on multiple factors. Patients treated with LDV/SOF with 8–24 weeks achieved SVR12 from 94% to 100% in the ION Phase 3 studies. A decision to shorten therapy to 8 weeks is based on treatment history, cirrhosis status and baseline viral load (VL). In a post-hoc analysis of the ION-3 (treatment naive (TN), non-cirrhotic (NC patients)) 8 week data, a VL < 6 M was shown to be the best predictor of SVR. Real world effectiveness (RWE) is often different from Phase III trials and there is a need to understand real-world 8 week regimens in a broader spectrum of patients. Methods: RWE 8 week LDV/SOF data is emerging from multiple single-center and multicenter retrospective and prospective cohorts. In this analysis, the phase-3 ION-3 data is compared with data from several diverse real world populations and one post-marketing investigator sponsored HIV/HCV trial. Patient demographics, characteristics, SVR12 and discontinuation data has been collated and compared. Results: The ION-3 post-hoc analysis reported 123 patients who were TN, NC and VL < 6 M and treated with 8 weeks of LDV/SOF. Mean age was 52, 22% black, 72% GT1a; the SVR12 was 97% (119/123). The overall SVR12 rate from six diverse real world and post marketing cohorts was also 97% (638/658). There was no significant impact of HCV genotypes or subtypes (GT1a, 1b versus GT4), prior treatment history, presence or absence of cirrhosis, high viral load (HCV VL > 6 M), or HIV/HCV co-infection. All response rates are detailed in Table 1.
Conclusions: LDV/SOF for 8 weeks yielded high SVR rates in ION-3. Analysis of RWE data from several diverse & heterogeneous cohorts from the US & EU show SVR outcomes that were consistent with the Phase-3 ION-3 results and supports the use of 8 weeks LDV/SOF in treatment-naive, non-cirrhotic GT1 patients with a baseline HCV VL < 6 M and possibly in other populations including HIV/HCV coinfected patients. Discontinuation rates were low despite diverse patients and clinical settings. Data from the TARGET and TRIO cohorts also suggests that the 8-week regimen is underutilized.
Journal of Hepatology 2016 vol. 64 | S631–S832
S810
SAT-242 LEDIPASVIR/SOFOSBUVIR (LDV/SOF) FOR 8 WKS IN GENOTYPE 1 (GT1) TREATMENT-NAÏVE NON-CIRRHOTIC PATIENTS WITH HCV VIRAL LOAD <6 MILLION IU/ML (6M); A COMPARATIVE ANALYSIS OF THE PHASE-3 ION-3 DATA TO REAL WORLD EFFECTIVENESS P. Buggisch1, J. Peterson1, S. Mauss2, K. Kowdley3, M. Curry4, P. Ruane5, D. Ain5, N. Tsai6, Y. Lee7, E. Eggleton8, M. Natha9, B. Kreter9, D. Brainard 9, P. Ingiliz10. 1IFI Institut für Interdisziplinäre Medizin, Asklepios Klinik St. Georg, Hamburg; 2Center for HIV and Hepatogastroenterology, Duesseldorf, Germany; 3Swedish Medical Center, Seattle; 4Beth Israel, Boston; 5Ruane Medical and Liver Health Institute, Los Angeles; 6Queens Medical Center, Honolulu; 7TRIO Health Analytics, Newton; 8Gilead Sciences, Los Angeles; 9Gilead Sciences, Foster City, United States; 10Medizinisches Infektiologie Zentrum, Berlin, Germany E-mail: [email protected] Background and Aims: The optimal duration of therapy to achieve SVR depends on multiple factors. Patients treated with LDV/SOF with 8–24 weeks achieved SVR12 from 94% to 100% in the ION Phase 3 studies. A decision to shorten therapy to 8 weeks is based on treatment history, cirrhosis status and baseline viral load (VL). In a post-hoc analysis of the ION-3 (treatment naive (TN), non-cirrhotic (NC patients)) 8 week data, a VL < 6 M was shown to be the best predictor of SVR. Real world effectiveness (RWE) is often different from Phase III trials and there is a need to understand real-world 8 week regimens in a broader spectrum of patients. Methods: RWE 8 week LDV/SOF data is emerging from multiple single-center and multicenter retrospective and prospective cohorts. In this analysis, the phase-3 ION-3 data is compared with data from several diverse real world populations and one post-marketing investigator sponsored HIV/HCV trial. Patient demographics, characteristics, SVR12 and discontinuation data has been collated and compared. Results: The ION-3 post-hoc analysis reported 123 patients who were TN, NC and VL < 6 M and treated with 8 weeks of LDV/SOF. Mean age was 52, 22% black, 72% GT1a; the SVR12 was 97% (119/123). The overall SVR12 rate from six diverse real world and post marketing cohorts was also 97% (638/658). There was no significant impact of HCV genotypes or subtypes (GT1a, 1b versus GT4), prior treatment history, presence or absence of cirrhosis, high viral load (HCV VL > 6 M), or HIV/HCV co-infection. All response rates are detailed in Table 1.
Conclusions: LDV/SOF for 8 weeks yielded high SVR rates in ION-3. Analysis of RWE data from several diverse & heterogeneous cohorts from the US & EU show SVR outcomes that were consistent with the Phase-3 ION-3 results and supports the use of 8 weeks LDV/SOF in treatment-naive, non-cirrhotic GT1 patients with a baseline HCV VL < 6 M and possibly in other populations including HIV/HCV coinfected patients. Discontinuation rates were low despite diverse patients and clinical settings. Data from the TARGET and TRIO cohorts also suggests that the 8-week regimen is underutilized.
Journal of Hepatology 2016 vol. 64 | S631–S832