Zobair M Younossi1, Maria Stepanova2, Stuart Gordon3, Stefan Zeuzem4, Michael P Mann5, Ira Jacobson6, Marc Bourliere7, Curtis Cooper8, Steven Flamm9, K Rajender Reddy10, Kris Kowdley11, Issah Younossi2, Sharon Hunt2. 1. Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia. Electronic address: zobair.younossi@inova.org. 2. Center for Outcomes Research Liver Diseases, Washington, District of Columbia. 3. Department of Gastroenterology, Henry Ford Hospital, Detroit, Michigan. 4. Klinikum der Johann Wolfgang Goethe-Universität, Medizinische Klinik 1, Frankfurt, Germany. 5. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. 6. The Mount Sinai Hospital, Mount Sinai Beth Israel, New York, New York. 7. Department of Hepato-Gastroenterology, Hospital Saint Joseph, Marseille, France. 8. Ottawa Hospital Research Institute, Ottawa, Canada. 9. Department of Hepato-Gastroenterology, Hospital Saint Joseph, Marseille, France; Northwestern University Medical School, Division of Gastroenterology and Hepatology, Chicago, Illinois. 10. University of Pennsylvania, Philadelphia, Pennsylvania. 11. Liver Care Network, Swedish Medical Center, Seattle, Washington.
Abstract
BACKGROUND & AIMS: Chronic infection with hepatitis C virus (HCV) has many hepatic and extrahepatic manifestations, measured by patient-reported outcomes (PROs). We measured changes in PROs during HCV treatment with recently developed pangenotypic regimens and from a sustained virologic response 12 weeks after treatment ended (SVR12). METHODS: We collected PRO data from 2 multi-center, blinded, international phase 3 trials of sofosbuvir, velpatasvir, and voxilaprevir, from 748 patients previously treated with direct-acting antivirals for chronic infection with HCV of any genotype (59% HCV genotype 1, 43% with compensated cirrhosis) (POLARIS-1 and POLARIS-4). The combination of sofosbuvir, velpatasvir, and voxilaprevir was given to 445 patients, the combination of sofosbuvir and velpatasvir to 151 patients, and placeboto 152 patients. Patients completed the SF-36, FACIT-F, CLDQ-HCV, and WPAI:SHP questionnaires at baseline, during treatment, and during the follow-up period. RESULTS: There was no difference in baseline clinical or demographic features or PRO scores among the groups (all P > .05). The group that received the combination of sofosbuvir, velpatasvir, and voxilaprevir had more gastrointestinal symptoms than the groups that received sofosbuvir and velpatasvir or placebo (P = .0001). An SVR12 was achieved by 90.1% of patients who received sofosbuvir and velpatasvir vs 96.9% of patients who received sofosbuvir, velpatasvir, and voxilaprevir (P = .0008). After 12 weeks of treatment, some PRO scores improved in both treatment groups (by 2.5 or by 9.1 points, on a 0-100 scale; P < .05) but not in the placebo group. All increases in PRO scores were sustained or increased after treatment ended (an increase of up to 11.1 points at 12 weeks after treatment and an increase of up to 16.6 points at 24 weeks after treatment ended) (P < .05 for all but 2 PROs). There were no differences in PROs between the sofosbuvir and velpatasvir group vs the sofosbuvir, velpatasvir, and voxilaprevir group (all P > .05). In multivariate analysis, after adjustment for clinical and demographic factors and baseline PRO scores, receiving treatment was associated with higher PROs scores than receiving placebo (beta as high as 5.1) (P < .05). CONCLUSIONS: In an analysis of data from 2 phase 3 clinical trials of patients with chronic HCV infection of any genotype, we found the combination of sofosbuvir, velpatasvir, with or without voxilaprevir, to increase PRO scores compared with placebo. These findings indicate the comprehensive benefit of these regimens during treatment and after SVR.
RCT Entities:
BACKGROUND & AIMS:Chronic infection with hepatitis C virus (HCV) has many hepatic and extrahepatic manifestations, measured by patient-reported outcomes (PROs). We measured changes in PROs during HCV treatment with recently developed pangenotypic regimens and from a sustained virologic response 12 weeks after treatment ended (SVR12). METHODS: We collected PRO data from 2 multi-center, blinded, international phase 3 trials of sofosbuvir, velpatasvir, and voxilaprevir, from 748 patients previously treated with direct-acting antivirals for chronic infection with HCV of any genotype (59% HCV genotype 1, 43% with compensated cirrhosis) (POLARIS-1 and POLARIS-4). The combination of sofosbuvir, velpatasvir, and voxilaprevir was given to 445 patients, the combination of sofosbuvir and velpatasvir to 151 patients, and placebo to 152 patients. Patients completed the SF-36, FACIT-F, CLDQ-HCV, and WPAI:SHP questionnaires at baseline, during treatment, and during the follow-up period. RESULTS: There was no difference in baseline clinical or demographic features or PRO scores among the groups (all P > .05). The group that received the combination of sofosbuvir, velpatasvir, and voxilaprevir had more gastrointestinal symptoms than the groups that received sofosbuvir and velpatasvir or placebo (P = .0001). An SVR12 was achieved by 90.1% of patients who received sofosbuvir and velpatasvir vs 96.9% of patients who received sofosbuvir, velpatasvir, and voxilaprevir (P = .0008). After 12 weeks of treatment, some PRO scores improved in both treatment groups (by 2.5 or by 9.1 points, on a 0-100 scale; P < .05) but not in the placebo group. All increases in PRO scores were sustained or increased after treatment ended (an increase of up to 11.1 points at 12 weeks after treatment and an increase of up to 16.6 points at 24 weeks after treatment ended) (P < .05 for all but 2 PROs). There were no differences in PROs between the sofosbuvir and velpatasvir group vs the sofosbuvir, velpatasvir, and voxilaprevir group (all P > .05). In multivariate analysis, after adjustment for clinical and demographic factors and baseline PRO scores, receiving treatment was associated with higher PROs scores than receiving placebo (beta as high as 5.1) (P < .05). CONCLUSIONS: In an analysis of data from 2 phase 3 clinical trials of patients with chronic HCV infection of any genotype, we found the combination of sofosbuvir, velpatasvir, with or without voxilaprevir, to increase PRO scores compared with placebo. These findings indicate the comprehensive benefit of these regimens during treatment and after SVR.
Authors: Bernd Schulte; Christiane S Schmidt; Jakob Manthey; Lisa Strada; Stefan Christensen; Konrad Cimander; Herbert Görne; Pavel Khaykin; Norbert Scherbaum; Stefan Walcher; Stefan Mauss; Ingo Schäfer; Uwe Verthein; Jürgen Rehm; Jens Reimer Journal: Open Forum Infect Dis Date: 2020-08-13 Impact factor: 3.835
Authors: Robert J Wong; Mamta K Jain; George Therapondos; Mitchell L Shiffman; Onkar Kshirsagar; Christopher Clark; Mae Thamer Journal: J Clin Exp Hepatol Date: 2019-09-20
Authors: Chris Davis; George S Mgomella; Ana da Silva Filipe; Eric H Frost; Genevieve Giroux; Joseph Hughes; Catherine Hogan; Pontiano Kaleebu; Gershim Asiki; John McLauchlan; Marc Niebel; Ponsiano Ocama; Cristina Pomila; Oliver G Pybus; Jacques Pépin; Peter Simmonds; Joshua B Singer; Vattipally B Sreenu; Clara Wekesa; Elizabeth H Young; Donald G Murphy; Manj Sandhu; Emma C Thomson Journal: Hepatology Date: 2019-03-22 Impact factor: 17.425