Salvatore Petta1, Marco Marzioni2, Pierluigi Russo3, Alessio Aghemo4, Alfredo Alberti5, Antonio Ascione6, Andrea Antinori7, Raffaele Bruno8, Savino Bruno9, Antonio Chirianni10, Giovanni Battista Gaeta11, Edoardo G Giannini12, Manuela Merli13, Vincenzo Messina14, Simona Montilla3, Carlo Federico Perno15, Massimo Puoti16, Giovanni Raimondo17, Maria Rendina18, Francesca Ceccherini Silberstein15, Erica Villa19, Anna Linda Zignego20, Luca Pani3, Antonio Craxì21. 1. Section of Gastroenterology and Hepatology, Biomedical Department of Internal and Specialized Medicine (DiBiMIS), University of Palermo, Palermo, Italy. Electronic address: salvatore.petta@unipa.it. 2. Clinic of Gastroenterology and Hepatology, Università Politecnica delle Marche, Ancona, Italy. 3. Italian Medicines Agency, Rome, Italy. 4. L'Unità Operativa Gastroenterologia ed Epatologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy. 5. Department of Molecular Medicine, University of Padova, Padova, Italy. 6. Centro per le malattie del Fegato, Ospedale Fatebenefratelli, Napoli, Italy. 7. National Institute for Infectious Diseases, "Lazzaro Spallanzani" Istituto di Ricovero e Cura a Carattere Scientific (IRCCS), Rome, Italy. 8. Dipartimento Malattie Infettive, Fondazione IRCCS Policlinico San Matteo Pavia Italia, Università degli studi di Pavia, Pavia, Italy. 9. Humanitas University and Humanitas Research Hospital Rozzano, Milan, Italy. 10. UOC Infezioni sistemiche e dell'immunodepresso, AO Ospedali dei Colli Napoli, Napoli, Italy. 11. Infectious Diseases and Viral Hepatitis, Second University of Naples, Naples, Italy. 12. Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy. 13. Gastroenterology Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy. 14. Infectious Diseases Unit, AORN Sant'Anna e San Sebastiano, Caserta, Italy. 15. Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy. 16. Department of Infectious Diseases, AO Niguarda Ca' Granda, Milan, Italy. 17. Division of Clinical and Molecular Hepatology, Department of Clinical and Experimental Medicine, University Hospital of Messina, Messina, Italy. 18. Gastroenterology and Digestive Endoscopy, University Hospital Policlinico Bari, Bari, Italy. 19. Division of Gastroenterology, Azienda Ospedaliero, Universitaria Policlinico di Modena, Italy Università degli Studi di Modena e Reggio Emilia, Modena, Italy. 20. Interdepartmental Centre MASVE, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy. 21. Section of Gastroenterology and Hepatology, Biomedical Department of Internal and Specialized Medicine (DiBiMIS), University of Palermo, Palermo, Italy.
Abstract
BACKGROUND: We ran a compassionate use nationwide programme (ABACUS) to provide access to ombitasvir, paritaprevir, and ritonavir, with dasabuvir, plus ribavirin for hepatitis C virus (HCV) genotype 1 infection and ombitasvir, paritaprevir, and ritonavir, plus ribavirin for HCV genotype 4 infection in patients with cirrhosis at high risk of decompensation while approval of these regimens was pending in Italy. METHODS: In this prospective observational study, we collected data from a compassionate use nationwide programme from March 17, 2014, to May 28, 2015. Patients with HCV genotype 1 infection and cirrhosis at high risk of decompensation were given coformulated ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) once daily and dasabuvir (250 mg) twice daily for 12 weeks (patients with HCV genotype 1b infection) or 24 weeks (patients with HCV genotype 1a infection). Patients with HCV genotype 4 infection were given coformulated ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) once per day for 24 weeks. All patients were given weight-based ribavirin. The primary efficacy endpoint was sustained virological response at week 12 after the end of treatment (SVR12), analysed by intention-to-treat. Univariate and multivariate logistic regression analyses were used to identify baseline characteristics associated with SVR12. Adverse events were recorded throughout the study. FINDINGS: 728 (96%) of 762 patients with cirrhosis who were given ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin therapy for 12 or 24 weeks achieved SVR12. Logistic regression analyses identified that bilirubin concentrations of less than 2 mg/dL were associated with SVR12 (odds ratio [OR] 4·76 [95% CI 1·83-12·3]; p=0·001). 166 (23%) of 734 patients included in safety analyses had an adverse event. 25 (3%) patients discontinued treatment because of adverse events. Asthenia was the most commonly reported adverse event, occurring in 36 (5%) patients. INTERPRETATION: Our findings suggest that the safety and effectiveness of ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin in patients with HCV genotype 1 or 4 infection and cirrhosis at high risk of decompensation in a real-life setting are similar to those reported in clinical trials. The concordance with clinical trials provides reassurance that the reported efficacy of this treatment in clinical trials will translate to its use in routine clinical practice. FUNDING: Dipartimento Biomedico di Medicina Interna e Specialistica dell'Universita di Palermo.
BACKGROUND: We ran a compassionate use nationwide programme (ABACUS) to provide access to ombitasvir, paritaprevir, and ritonavir, with dasabuvir, plus ribavirin for hepatitis C virus (HCV) genotype 1 infection and ombitasvir, paritaprevir, and ritonavir, plus ribavirin for HCV genotype 4 infection in patients with cirrhosis at high risk of decompensation while approval of these regimens was pending in Italy. METHODS: In this prospective observational study, we collected data from a compassionate use nationwide programme from March 17, 2014, to May 28, 2015. Patients with HCV genotype 1 infection and cirrhosis at high risk of decompensation were given coformulated ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) once daily and dasabuvir (250 mg) twice daily for 12 weeks (patients with HCV genotype 1b infection) or 24 weeks (patients with HCV genotype 1a infection). Patients with HCV genotype 4 infection were given coformulated ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) once per day for 24 weeks. All patients were given weight-based ribavirin. The primary efficacy endpoint was sustained virological response at week 12 after the end of treatment (SVR12), analysed by intention-to-treat. Univariate and multivariate logistic regression analyses were used to identify baseline characteristics associated with SVR12. Adverse events were recorded throughout the study. FINDINGS: 728 (96%) of 762 patients with cirrhosis who were given ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin therapy for 12 or 24 weeks achieved SVR12. Logistic regression analyses identified that bilirubin concentrations of less than 2 mg/dL were associated with SVR12 (odds ratio [OR] 4·76 [95% CI 1·83-12·3]; p=0·001). 166 (23%) of 734 patients included in safety analyses had an adverse event. 25 (3%) patients discontinued treatment because of adverse events. Asthenia was the most commonly reported adverse event, occurring in 36 (5%) patients. INTERPRETATION: Our findings suggest that the safety and effectiveness of ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin in patients with HCV genotype 1 or 4 infection and cirrhosis at high risk of decompensation in a real-life setting are similar to those reported in clinical trials. The concordance with clinical trials provides reassurance that the reported efficacy of this treatment in clinical trials will translate to its use in routine clinical practice. FUNDING: Dipartimento Biomedico di Medicina Interna e Specialistica dell'Universita di Palermo.
Authors: Antonio Ascione; Massimo De Luca; Mario Melazzini; Simona Montilla; Maria Paola Trotta; Salvatore Petta; Massimo Puoti; Vincenzo Sangiovanni; Vincenzo Messina; Savino Bruno; Antonio Izzi; Erica Villa; Alessio Aghemo; Anna Linda Zignego; Alessandra Orlandini; Luca Fontanella; Antonio Gasbarrini; Marco Marzioni; Edoardo G Giannini; Antonio Craxì Journal: Infection Date: 2018-05-28 Impact factor: 7.455