Ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin for patients with hepatitis C virus genotype 1 or 4 infection with cirrhosis (ABACUS): a prospective observational study

Salvatore Petta, Marco Marzioni, Pierluigi Russo, Alessio Aghemo, Alfredo Alberti, Antonio Ascione, Andrea Antinori, Raffaele Bruno, Savino Bruno, Antonio Chirianni, Giovanni Battista Gaeta, Edoardo G. Giannini, Manuela Merli, Vincenzo Messina, Simona Montilla, Carlo Federico Perno, Massimo Puoti, Giovanni Raimondo, Maria Rendina, Francesca Ceccherini SilbersteinErica Villa, Anna Linda Zignego, Luca Pani, Antonio Craxì, Marco Tabone, Massimo Andreoni, Elisabetta Teti, Mario Angelico, Marcello Persico, Mario Masarone, Aledssandro Chiodera, Attilio Solinas, Marco delle Monache, Roberto Cecere, Maria Vinci, Michele Milella, Carlo Ferrari, Serena Cima, Raffaele Cozzolongo, Giovanna Onnelli, Raffaella Lionetti, Marzia Montalbano, Cristina Rossi, Antonio Cristaudo, Massimo Colombo, Maria Grazia Rumi, Roberto Gulminetti, Renato Maserati, Mario Mondelli, Adriano Lazzarin, on behalf of the, ABACUS study group, the, AIFA team, ABACUS study group, the, AIFA team, the, AIFA team, AIFA team

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)427-434
Number of pages8
JournalThe Lancet Gastroenterology and Hepatology
Volume2
Issue number6
DOIs
Publication statusPublished - Jun 1 2017

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Ritonavir
Ribavirin
Hepacivirus
Observational Studies
Fibrosis
Genotype
Prospective Studies
Infection
Compassionate Use Trials
Clinical Trials
ABT-450
ABT-267
ABT-333
Logistic Models
Regression Analysis
Safety
Asthenia
Bilirubin
Italy
Therapeutics

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

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Ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin for patients with hepatitis C virus genotype 1 or 4 infection with cirrhosis (ABACUS) : a prospective observational study. / Petta, Salvatore; Marzioni, Marco; Russo, Pierluigi; Aghemo, Alessio; Alberti, Alfredo; Ascione, Antonio; Antinori, Andrea; Bruno, Raffaele; Bruno, Savino; Chirianni, Antonio; Gaeta, Giovanni Battista; Giannini, Edoardo G.; Merli, Manuela; Messina, Vincenzo; Montilla, Simona; Perno, Carlo Federico; Puoti, Massimo; Raimondo, Giovanni; Rendina, Maria; Silberstein, Francesca Ceccherini; Villa, Erica; Zignego, Anna Linda; Pani, Luca; Craxì, Antonio; Tabone, Marco; Andreoni, Massimo; Teti, Elisabetta; Angelico, Mario; Persico, Marcello; Masarone, Mario; Chiodera, Aledssandro; Solinas, Attilio; delle Monache, Marco; Cecere, Roberto; Vinci, Maria; Milella, Michele; Ferrari, Carlo; Cima, Serena; Cozzolongo, Raffaele; Onnelli, Giovanna; Lionetti, Raffaella; Montalbano, Marzia; Rossi, Cristina; Cristaudo, Antonio; Colombo, Massimo; Grazia Rumi, Maria; Gulminetti, Roberto; Maserati, Renato; Mondelli, Mario; Lazzarin, Adriano; on behalf of the; ABACUS study group; the; AIFA team; ABACUS study group; the; AIFA team; the; AIFA team; AIFA team.

In: The Lancet Gastroenterology and Hepatology, Vol. 2, No. 6, 01.06.2017, p. 427-434.

Research output: Contribution to journalArticle

Petta, S, Marzioni, M, Russo, P, Aghemo, A, Alberti, A, Ascione, A, Antinori, A, Bruno, R, Bruno, S, Chirianni, A, Gaeta, GB, Giannini, EG, Merli, M, Messina, V, Montilla, S, Perno, CF, Puoti, M, Raimondo, G, Rendina, M, Silberstein, FC, Villa, E, Zignego, AL, Pani, L, Craxì, A, Tabone, M, Andreoni, M, Teti, E, Angelico, M, Persico, M, Masarone, M, Chiodera, A, Solinas, A, delle Monache, M, Cecere, R, Vinci, M, Milella, M, Ferrari, C, Cima, S, Cozzolongo, R, Onnelli, G, Lionetti, R, Montalbano, M, Rossi, C, Cristaudo, A, Colombo, M, Grazia Rumi, M, Gulminetti, R, Maserati, R, Mondelli, M, Lazzarin, A, on behalf of the, ABACUS study group, the, AIFA team, ABACUS study group, the, AIFA team, the, AIFA team & AIFA team 2017, 'Ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin for patients with hepatitis C virus genotype 1 or 4 infection with cirrhosis (ABACUS): a prospective observational study', The Lancet Gastroenterology and Hepatology, vol. 2, no. 6, pp. 427-434. https://doi.org/10.1016/S2468-1253(17)30048-1
Petta, Salvatore ; Marzioni, Marco ; Russo, Pierluigi ; Aghemo, Alessio ; Alberti, Alfredo ; Ascione, Antonio ; Antinori, Andrea ; Bruno, Raffaele ; Bruno, Savino ; Chirianni, Antonio ; Gaeta, Giovanni Battista ; Giannini, Edoardo G. ; Merli, Manuela ; Messina, Vincenzo ; Montilla, Simona ; Perno, Carlo Federico ; Puoti, Massimo ; Raimondo, Giovanni ; Rendina, Maria ; Silberstein, Francesca Ceccherini ; Villa, Erica ; Zignego, Anna Linda ; Pani, Luca ; Craxì, Antonio ; Tabone, Marco ; Andreoni, Massimo ; Teti, Elisabetta ; Angelico, Mario ; Persico, Marcello ; Masarone, Mario ; Chiodera, Aledssandro ; Solinas, Attilio ; delle Monache, Marco ; Cecere, Roberto ; Vinci, Maria ; Milella, Michele ; Ferrari, Carlo ; Cima, Serena ; Cozzolongo, Raffaele ; Onnelli, Giovanna ; Lionetti, Raffaella ; Montalbano, Marzia ; Rossi, Cristina ; Cristaudo, Antonio ; Colombo, Massimo ; Grazia Rumi, Maria ; Gulminetti, Roberto ; Maserati, Renato ; Mondelli, Mario ; Lazzarin, Adriano ; on behalf of the ; ABACUS study group ; the ; AIFA team ; ABACUS study group ; the ; AIFA team ; the ; AIFA team ; AIFA team. / Ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin for patients with hepatitis C virus genotype 1 or 4 infection with cirrhosis (ABACUS) : a prospective observational study. In: The Lancet Gastroenterology and Hepatology. 2017 ; Vol. 2, No. 6. pp. 427-434.
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title = "Ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin for patients with hepatitis C virus genotype 1 or 4 infection with cirrhosis (ABACUS): a prospective observational study",
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.",
author = "Salvatore Petta and Marco Marzioni and Pierluigi Russo and Alessio Aghemo and Alfredo Alberti and Antonio Ascione and Andrea Antinori and Raffaele Bruno and Savino Bruno and Antonio Chirianni and Gaeta, {Giovanni Battista} and Giannini, {Edoardo G.} and Manuela Merli and Vincenzo Messina and Simona Montilla and Perno, {Carlo Federico} and Massimo Puoti and Giovanni Raimondo and Maria Rendina and Silberstein, {Francesca Ceccherini} and Erica Villa and Zignego, {Anna Linda} and Luca Pani and Antonio Crax{\`i} and Marco Tabone and Massimo Andreoni and Elisabetta Teti and Mario Angelico and Marcello Persico and Mario Masarone and Aledssandro Chiodera and Attilio Solinas and {delle Monache}, Marco and Roberto Cecere and Maria Vinci and Michele Milella and Carlo Ferrari and Serena Cima and Raffaele Cozzolongo and Giovanna Onnelli and Raffaella Lionetti and Marzia Montalbano and Cristina Rossi and Antonio Cristaudo and Massimo Colombo and {Grazia Rumi}, Maria and Roberto Gulminetti and Renato Maserati and Mario Mondelli and Adriano Lazzarin and {on behalf of the} and {ABACUS study group} and the and {AIFA team} and {ABACUS study group} and the and {AIFA team} and the and {AIFA team} and {AIFA team}",
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TY - JOUR

T1 - Ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin for patients with hepatitis C virus genotype 1 or 4 infection with cirrhosis (ABACUS)

T2 - a prospective observational study

AU - Petta, Salvatore

AU - Marzioni, Marco

AU - Russo, Pierluigi

AU - Aghemo, Alessio

AU - Alberti, Alfredo

AU - Ascione, Antonio

AU - Antinori, Andrea

AU - Bruno, Raffaele

AU - Bruno, Savino

AU - Chirianni, Antonio

AU - Gaeta, Giovanni Battista

AU - Giannini, Edoardo G.

AU - Merli, Manuela

AU - Messina, Vincenzo

AU - Montilla, Simona

AU - Perno, Carlo Federico

AU - Puoti, Massimo

AU - Raimondo, Giovanni

AU - Rendina, Maria

AU - Silberstein, Francesca Ceccherini

AU - Villa, Erica

AU - Zignego, Anna Linda

AU - Pani, Luca

AU - Craxì, Antonio

AU - Tabone, Marco

AU - Andreoni, Massimo

AU - Teti, Elisabetta

AU - Angelico, Mario

AU - Persico, Marcello

AU - Masarone, Mario

AU - Chiodera, Aledssandro

AU - Solinas, Attilio

AU - delle Monache, Marco

AU - Cecere, Roberto

AU - Vinci, Maria

AU - Milella, Michele

AU - Ferrari, Carlo

AU - Cima, Serena

AU - Cozzolongo, Raffaele

AU - Onnelli, Giovanna

AU - Lionetti, Raffaella

AU - Montalbano, Marzia

AU - Rossi, Cristina

AU - Cristaudo, Antonio

AU - Colombo, Massimo

AU - Grazia Rumi, Maria

AU - Gulminetti, Roberto

AU - Maserati, Renato

AU - Mondelli, Mario

AU - Lazzarin, Adriano

AU - on behalf of the

AU - ABACUS study group

AU - the

AU - AIFA team

AU - ABACUS study group

AU - the

AU - AIFA team

AU - the

AU - AIFA team

AU - AIFA team

PY - 2017/6/1

Y1 - 2017/6/1

N2 - 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.

AB - 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.

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EP - 434

JO - The Lancet Gastroenterology and Hepatology

JF - The Lancet Gastroenterology and Hepatology

SN - 2468-1253

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