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Rodrigues JPV, Cazarim MDS, Chachá SGF, Martinelli ADLC, Pereira LRL. Cost-effectiveness analysis is a mandatory strategy for health systems: evidence from a study involving therapies for hepatitis C. CAD SAUDE PUBLICA 2020; 36:e00036619. [PMID: 32022174 DOI: 10.1590/0102-311x00036619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Accepted: 08/02/2019] [Indexed: 11/22/2022] Open
Abstract
Cost-effectiveness analysis is essential in health decision making. Several countries use it as synthesis of evidence to incorporate health technologies. The protease inhibitors (PI) boceprevir (BOC) and telaprevir (TVR) are indicated for chronic hepatitis C treatment and were incorporated in guidelines worldwide. Pre-marketing clinical trials showed higher sustained virological response rates in relation to previous therapies, but the incorporation of PIs generated a significant financial impact. The aim of this study was to discuss the relevance of cost-effectiveness analysis through a study that involved the inclusion of PIs in a clinical protocol. The analysis was part of a real-life study that included patients infected with hepatitis C virus genotype 1 treated in a tertiary university hospital in Brazil. Triple therapies (TT) with ribavirin (RBV), peginterferon α-2a (Peg-INF α-2a) and BOC or TVR were compared to dual therapy with RBV and Peg-INF α-2a. Sensitivity analysis of the cost-effectiveness ratio indicated an 88.2% chance of TTs presenting a higher cost per cure. The incremental cost-effectiveness ratios (ICER) exceeded the Brazilian gross domestic product (GDP) per capita by three times in all proposed scenarios. The sensitivity of ICER showed an 88.4% chance of TT not being cost-effective. The impact of PI incorporation was negative and the conduct about this could have been different if a previous cost-effectiveness analysis had been conducted.
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Affiliation(s)
- João Paulo Vilela Rodrigues
- Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brasil.,Faculdade de Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brasil
| | - Maurílio de Souza Cazarim
- Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brasil
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Bach TA, Zaiken K. Outcomes of treatment with direct-acting antivirals for infection with hepatitis C virus genotypes 1-4 in an ambulatory care setting. Am J Health Syst Pharm 2019; 74:S1-S9. [PMID: 28213381 DOI: 10.2146/ajhp160567] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
PURPOSE Outcomes with direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) genotypes 1-4 were determined. METHODS A total of 360 patients at 36 clinical sites in Massachusetts with HCV genotypes 1-4 and a prescription for at least one DAA medication between May 2011 and October 2015 were included. The primary investigator completed a retrospective and concurrent chart review, and data were collected through April 2016. RESULTS A total of 446 patients were assessed for eligibility into the study, with 86 patients excluded. The majority of patients were white males with genotype 1 infection. About half of the patients were treatment naive (TN), and 40% of patients had documented cirrhosis. TN patients without cirrhosis had the highest overall sustained virologic response (SVR) rate at 107 of 109 (98.2%), followed by treatment-experienced (TE) patients without cirrhosis at 59 of 63 (93.7%), TN patients with cirrhosis at 40 of 46 (87.0%), and TE patients with cirrhosis at 64 of 79 (81.0%) when boceprevir- and telaprevir-containing regimens were excluded. A total of 7 of 360 (1.9%) patients reported missing at least one dose of medication. Adverse drug reactions reported in the electronic medical record (EMR) were collected for analysis and included patients who received at least one dose of medication and had adequate EMR documentation. CONCLUSION In patients treated with DAAs for infection with HCV genotypes 1-4, variables favoring achievement of SVR included an age of <45 years, a body mass index of <25 kg/m2, absence of cirrhosis, a fibrosis score of 0-2, and being TN.
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Chachá SGF, Rodrigues JPV, Araújo RC, Pereira LRL, Villanova MG, Souza FF, Santana RDC, Martinelli ADLC. First-wave protease inhibitors for hepatitis C genotype 1 treatment: a real-life experience in Brazilian patients. Rev Soc Bras Med Trop 2018; 51:146-154. [PMID: 29768546 DOI: 10.1590/0037-8682-0153-2017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2017] [Accepted: 03/28/2018] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION Licensed for chronic hepatitis C treatment in 2011, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC), which have high sustained viral responses (SVR), ushered a new era characterized by the development of direct-action drugs against the hepatitis C virus (HCV). The aim of this study was to analyze the effectiveness and safety of BOC and TVR administered with pegylated interferon and ribavirin and to share the experience of a Brazilian reference center. METHODS A retrospective descriptive study was conducted in patients with HCV genotype 1 infection who started treatment between July 2013 and December 2015. Data were collected using a computerized system. RESULTS A total of 115 subjects were included, of which 58 (50.4 %) had liver cirrhosis and 103 (89.6 %) used TVR. The overall SVR rate was 61.7 % (62.1 % for TVR and 58.3 % for BOC). The presence of cirrhosis was associated with a lower SVR rate, whereas patients who relapsed after prior therapy had a greater chance of showing SVR than did non-responders. The incidence of adverse drug reactions (ADRs) was high. Almost all patients (~100 %) presented with hematologic events. Furthermore, treatment had to be discontinued in 15 subjects (13 %) due to severe ADRs. CONCLUSIONS In conclusion, the SVR rates in our study were lower than those reported in pre-marketing studies but were comparable to real-life data. ADRs, particularly hematological ADRs, were more common compared to those in previous studies and resulted in a high rate of treatment discontinuity.
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Affiliation(s)
- Silvana Gama Florencio Chachá
- Departamento de Medicina, Universidade Federal de São Carlos, São Carlos, SP, Brasil.,Divisão de Gastroenterologia, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil
| | - João Paulo Vilela Rodrigues
- Centro de Pesquisa em Assistência Farmacêutica e Farmácia Clínica, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil
| | - Roberta Chaves Araújo
- Divisão de Gastroenterologia, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil
| | - Leonardo Régis Leira Pereira
- Centro de Pesquisa em Assistência Farmacêutica e Farmácia Clínica, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil
| | - Márcia Guimarães Villanova
- Divisão de Gastroenterologia, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil
| | - Fernanda Fernandes Souza
- Divisão de Gastroenterologia, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil
| | - Rodrigo de Carvalho Santana
- Divisão de Moléstias Infecciosas, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil
| | - Ana de Lourdes Candolo Martinelli
- Divisão de Gastroenterologia, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil
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Mangia A, De Ledinghen V, Bailly F, Brahm J, Keiss J, Valantinas J, Rasmann N, Messinger D, Tatsch F, Bakalos G, Foster GR. IL28B genotype is associated with cirrhosis or transition to cirrhosis in treatment-naive patients with chronic HCV genotype 1 infection: the international observational Gen-C study. SPRINGERPLUS 2016; 5:1990. [PMID: 27917361 PMCID: PMC5116020 DOI: 10.1186/s40064-016-3663-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/15/2016] [Accepted: 11/07/2016] [Indexed: 02/07/2023]
Abstract
Background and purpose Contradictory data exist on the association between host interleukin-28B (IL28B) rs12979860 genotype and liver fibrosis in patients with chronic hepatitis C (CHC). This large, international, observational study (NCT01675427/MV25600) investigated relationships between IL28B rs12979860 genotype and liver fibrosis stage in CHC patients. Methods A total of 3003 adult, treatment-naive CHC patients were enrolled into the study. Patients made one study visit to provide a blood sample for genotyping; other data were obtained from medical records. Results 2916 patients comprised the analysis population; the majority were enrolled in Europe (n = 2119), were Caucasian (n = 2582) and had hepatitis C virus (HCV) genotype (G)1 infection (n = 1702) (G2 = 323, G3 = 574, G4 = 260). Distribution of IL28B genotypes varied according to region of enrolment, patient ethnicity and HCV genotype. A significant association was observed between increasing number of IL28B T alleles and the prevalence of cirrhosis/transition to cirrhosis (based on biopsy or non-invasive assessments) in G1-infected patients (CC = 22.2% [111/499], CT = 27.5% [255/928], TT = 32.3% [87/269]; p = 0.0018). The association was significant in the large subgroup of European Caucasian G1 patients (n = 1245) but not in the smaller Asian (n = 25), Latin American (n = 137) or Middle Eastern (n = 289) G1 subgroups. IL28B genotype was not associated with liver fibrosis stage in patients with HCV G2, G3 or G4 infection. Conclusion This large, international study found that IL28B rs12979860 genotype is significantly associated with liver fibrosis stage in CHC patients with HCV G1 infection. This association was evident in European Caucasians but not in G1-infected patients from Asia, Latin America or the Middle East. Electronic supplementary material The online version of this article (doi:10.1186/s40064-016-3663-6) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Alessandra Mangia
- Liver Unit, IRCCS Hospital 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, 71013 Italy
| | | | - François Bailly
- Hepatology Unit, Groupe Hospitalier Nord, CHU Lyon, 69004 Lyon, France
| | - Javier Brahm
- Gastroenterology Department, University of Chile Clinical Hospital, Santiago, 8380456 Chile
| | - Jazeps Keiss
- Latvian Centre of Infectious Diseases, LLC Riga East University Hospital, Riga, 1006 Latvia
| | - Jonas Valantinas
- Centre of Hepatology, Gastroenterology and Dietetics, Vilnius University, 08661 Vilnius, Lithuania
| | - Nele Rasmann
- Center for Infectious Diseases, West Tallinn Central Hospital, 10617 Tallinn, Estonia
| | | | - Fernando Tatsch
- Global Medical Affairs, F. Hoffmann-La Roche Ltd, 4074 Basel, Switzerland ; AbbVie, North Chicago, IL USA
| | - Georgios Bakalos
- Global Product Development Medical Affairs, F. Hoffmann-La Roche Ltd, 4074 Basel, Switzerland
| | - Graham R Foster
- Institute of Cellular and Molecular Sciences, Queen Mary University of London, London, E1 2AT UK
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Gray E, Norris S, Schmitz S, O'Leary A. Do disparities between populations in randomized controlled trials and the real world lead to differences in outcomes? J Comp Eff Res 2016; 6:65-82. [PMID: 27854129 DOI: 10.2217/cer-2016-0042] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To conduct a systematic review investigating reasons for the disparity between the efficacy and effectiveness rates reported in randomized controlled trials (RCTs) and observational studies of direct-acting antiviral treatment regimens licensed for use in genotype1 hepatitis C virus-infected individuals. METHODS This systematic review was conducted in accordance with the criteria of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses group. RESULTS Statistically significant (p < 0.05) differences in the baseline demographics and sustained virological response rates were observed between RCT and observational studies. CONCLUSION In order for outcomes from RCTs to be generalizable to the real world, greater consideration needs to be taken to include patient populations that are more representative of those awaiting treatment in the clinical setting.
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Affiliation(s)
- Emma Gray
- School of Medicine, Trinity College Dublin, Dublin, Ireland
| | - Suzanne Norris
- School of Medicine, Trinity College Dublin, Dublin, Ireland.,Departmentof Hepatology, St James' Hospital, Dublin, Ireland
| | - Susanne Schmitz
- HealthEconomics & Evidence Synthesis Research Unit, Department of PopulationHealth, Luxembourg Health Institute, Luxembourg
| | - Aisling O'Leary
- Schoolof Pharmacy, Royal College of Surgeons of Ireland, Dublin, Ireland.,NationalCentre for Pharmacoeconomics, St James' Hospital, Dublin, Ireland
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Alric L, Besson C, Lapidus N, Jeannel J, Michot JM, Cacoub P, Canioni D, Pol S, Davi F, Rabiega P, Ysebaert L, Bonnet D, Hermine O. Antiviral Treatment of HCV-Infected Patients with B-Cell Non-Hodgkin Lymphoma: ANRS HC-13 Lympho-C Study. PLoS One 2016; 11:e0162965. [PMID: 27749916 PMCID: PMC5066969 DOI: 10.1371/journal.pone.0162965] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2016] [Accepted: 08/31/2016] [Indexed: 12/31/2022] Open
Abstract
Hepatitis C virus (HCV) infection is associated with lymphoproliferative disorders and B-cell non-Hodgkin lymphomas (B-NHLs). Evaluation of the efficacy and safety profiles of different antiviral therapies in HCV patients with B-NHL is warranted. METHODS First, we evaluated the sustained virologic response (SVR) and safety of Peg-interferon-alpha (Peg-IFN) + ribavirin +/- first protease inhibitors (PI1s) therapy in 61 HCV patients with B-NHL enrolled in a nationwide observational survey compared with 94 matched HCV-infected controls without B-NHL. In a second series, interferon-free regimens using a newly optimal combination therapy with direct-acting antiviral drugs (DAAs) were evaluated in 10 patients with HCV and B-NHL. RESULTS The main lymphoma type was diffuse large B-cell lymphoma (38%) followed by marginal zone lymphoma (31%). In the multivariate analysis, patients with B-NHL treated by Peg-IFN-based therapy exhibited a greater SVR rate compared with controls, 50.8% vs 30.8%, respectively, p<0.01, odds ratio (OR) = 11.2 [2.3, 52.8]. B-NHL response was better (p = 0.02) in patients with SVR (69%) than in patients without SVR (31%). Premature discontinuation of Peg-IFN-based therapy was significantly more frequent in the B-NHL group (19.6%) compared with the control group (6.3%), p<0.02. Overall, survival was significantly enhanced in the controls than in the B-NHL group (hazard ratio = 34.4 [3.9, 304.2], p< 0.01). Using DAAs, SVR was achieved in 9/10 patients (90%). DAAs were both well tolerated and markedly efficient. CONCLUSIONS The virologic response of HCV-associated B-NHL is high. Our study provides a comprehensive evaluation of different strategies for the antiviral treatment of B-NHL associated with HCV infection.
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Affiliation(s)
- Laurent Alric
- Department of Internal Medicine and Digestive Diseases, CHU Purpan, UMR 152, IRD Toulouse 3 University, Toulouse, France
| | - Caroline Besson
- Université Paris sud Faculté de Médecine Kremlin Bicêtre, AP-HP Hôpital Bicêtre, Le Kremlin-Bicêtre, IMVA INSERM U1184, Paris, France
| | - Nathanael Lapidus
- Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d’épidémiologie et de Santé Publique (IPLESP UMRS 1136), Department of Public Health, Hôpital Saint-Antoine, AP-HP, Paris, France
| | - Juliette Jeannel
- Department of Internal Medicine and Digestive Diseases, CHU Purpan, UMR 152, IRD Toulouse 3 University, Toulouse, France
| | - Jean-Marie Michot
- Université Paris sud Faculté de Médecine Kremlin Bicêtre, AP-HP Hôpital Bicêtre, Le Kremlin-Bicêtre, IMVA INSERM U1184, Paris, France
| | - Patrice Cacoub
- Paris 6 Pierre et Marie Curie University, UMR 7211, INSERM, UMR S 959, CNRS, UMR 7211, AP-HP, Department of Internal Medicine, Hôpital Pitié-Salpêtrière, Paris, France
| | - Danielle Canioni
- Paris 5 Descartes University, AP-HP, Department of Pathology, Hôpital Necker, Paris, France
| | - Stanislas Pol
- Université Descartes, Inserm U-318 Institut Pasteur, AP-HP, Department of hepatology, Hôpital Cochin, Paris, France
| | - Frédéric Davi
- Paris 6 Pierre et Marie Curie University, AP-HP, Department of Biological Hematology and Cytogenetic, Hôpital Pitié-Salpêtrière, Paris, France
| | - Pascaline Rabiega
- Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d’épidémiologie et de Santé Publique (IPLESP UMRS 1136), Department of Public Health, Hôpital Saint-Antoine, AP-HP, Paris, France
| | - Loic Ysebaert
- Department of Hematology IUCT oncopole, CHU, Toulouse, France
| | - Delphine Bonnet
- Department of Internal Medicine and Digestive Diseases, CHU Purpan, UMR 152, IRD Toulouse 3 University, Toulouse, France
| | - Olivier Hermine
- Paris 5 Descartes University, AP-HP, INSERM U 1163, CNRS ERL 8254, Department of Adult Hematology and Imagine Institute, Hôpital Necker, Paris, France
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Treatment Selection Choices Should Not Be Based on Benefits or Costs Alone: A Head-to-Head Randomized Controlled Trial of Antiviral Drugs for Hepatitis C. PLoS One 2016; 11:e0163945. [PMID: 27741230 PMCID: PMC5065164 DOI: 10.1371/journal.pone.0163945] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Accepted: 09/04/2016] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Clinicians often face dilemmas with decisions related to formulary choices when two similar drugs are simultaneously available in the market. We studied the comparative safety, effectiveness, and treatment costs of the two first generation direct-acting antiviral agents (DAA), boceprevir and telaprevir as uncertainty existed regarding the drug of choice between these two seemingly equally Hepatitis-C treatment options. METHODS We randomly assigned 50 patients in an open-label, pragmatic randomized controlled trial (RCT) at a VA Medical Center to either boceprevir or telaprevir in combination with peginterferon and ribavirin, stratified by the presence of cirrhosis and prior treatment experience. Tolerability was assessed at each visit and reasons for discontinuation of treatment and severity of adverse events due to PI treatment were adjudicated using a blinded adjudication committee. The primary outcome was difference in tolerability between boceprevir vs. telaprevir. Secondary outcomes included viral response rates and cost-per cure achieved. RESULTS Higher rates of treatment discontinuations and/or severe DAA associated adverse events were seen in 10/25 (40%) patients randomized to telaprevir compared to 2/25 (8%) patients randomized to boceprevir (RR: 5; 95% CI: 1.2, 20; p<0.01). Cure rates did not appear to be significantly different between groups (telaprevir vs. boceprevir: RR 1.23; 95% CI: 0.76, 1.99; p = 0.39). On an intention-to-treat basis, total cost per cure was $44,329 for boceprevir vs. $57,115 for telaprevir. The significant side effect profile of telaprevir combined with the availability of highly efficacious second generation DAAs led to the early discontinuation of the trial. CONCLUSION Telaprevir is associated with a significantly higher rate of severe adverse events leading to treatment discontinuations, hospitalizations or severe anemia and a substantially higher cost per SVR when compared to boceprevir. Real-time, point of care, pragmatic randomized controlled trials are necessary for guidance beyond just acquisition costs and to make evidence-based formulary selections when multiple effective treatments are available. (Clinicaltrials.gov registration: NCT02113631).
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CLEO Study Group, Ascione A, Adinolfi LE, Amoroso P, Andriulli A, Armignacco O, Ascione T, Babudieri S, Barbarini G, Brogna M, Cesario F, Citro V, Claar E, Cozzolongo R, D’Adamo G, D’Amico E, Dattolo P, De Luca M, De Maria V, De Siena M, De Vita G, Di Giacomo A, De Marco R, De Stefano G, De Stefano G, Di Salvo S, Di Sarno R, Farella N, Felicioni L, Fimiani B, Fontanella L, Foti G, Furlan C, Giancotti F, Giolitto G, Gravina T, Guerrera B, Gulminetti R, Iacobellis A, Imparato M, Iodice A, Iovinella V, Izzi A, Liberti A, Leo P, Lettieri G, Luppino I, Marrone A, Mazzoni E, Messina V, Monarca R, Narciso V, Nosotti L, Pellicelli AM, Perrella A, Piai G, Picardi A, Pierri P, Pietromatera G, Resta F, Rinaldi L, Romano M, Rossini A, Russello M, Russo G, Sacco R, Sangiovanni V, Schiano A, Sciambra A, Scifo G, Simeone F, Sullo A, Tarquini P, Tundo P, Vallone A. Boceprevir or telaprevir in hepatitis C virus chronic infection: The Italian real life experience. World J Hepatol 2016; 8:949-956. [PMID: 27574549 PMCID: PMC4976214 DOI: 10.4254/wjh.v8.i22.949] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2016] [Revised: 06/23/2016] [Accepted: 07/22/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To check the safety and efficacy of boceprevir/telaprevir with peginterferon/ribavirin for hepatitis C virus (HCV) genotype 1 in the real-world settings.
METHODS: This study was a non-randomized, observational, prospective, multicenter. This study involved 47 centers in Italy. A database was prepared for the homogenous collection of the data, was used by all of the centers for data collection, and was updated continuously. All of the patients enrolled in this study were older than 18 years of age and were diagnosed with chronic infection due to HCV genotype 1. The HCV RNA testing was performed using COBAS-TaqMan2.0 (Roche, LLQ 25 IU/mL).
RESULTS: All consecutively treated patients were included. Forty-seven centers enrolled 834 patients as follows: Male 64%; median age 57 (range 18-78), of whom 18.3% were over 65; mean body mass index 25.6 (range 16-39); genotype 1b (79.4%); diagnosis of cirrhosis (38.2%); and fibrosis F3/4 (71.2%). The following drugs were used: Telaprevir (66.2%) and PEG-IFN-alpha2a (67.6%). Patients were naïve (24.4%), relapsers (30.5%), partial responders (14.8%) and null responders (30.3%). Overall, adverse events (AEs) occurred in 617 patients (73.9%) during the treatment. Anemia was the most frequent AE (52.9% of cases), especially in cirrhotic. The therapy was stopped for 14.6% of the patients because of adverse events or virological failure (15%). Sustained virological response was achieved in 62.7% of the cases, but was 43.8% in cirrhotic patients over 65 years of age.
CONCLUSION: In everyday practice, triple therapy is safe but has moderate efficacy, especially for patients over 65 years of age, with advanced fibrosis, non-responders to peginterferon + ribavirin.
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Boursier J, Ducancelle A, Vergniol J, Veillon P, Moal V, Dufour C, Bronowicki JP, Larrey D, Hézode C, Zoulim F, Fontaine H, Canva V, Poynard T, Allam S, De Lédinghen V. The CUPIC algorithm: an accurate model for the prediction of sustained viral response under telaprevir or boceprevir triple therapy in cirrhotic patients. J Viral Hepat 2015. [PMID: 26216230 DOI: 10.1111/jvh.12433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
Triple therapy using boceprevir or telaprevir remains the reference treatment for genotype 1 chronic hepatitis C in countries where new interferon-free regimens have not yet become available. Antiviral treatment is highly required in cirrhotic patients, but they represent a difficult-to-treat population. We aimed to develop a simple algorithm for the prediction of sustained viral response (SVR) in cirrhotic patients treated with triple therapy. A total of 484 cirrhotic patients from the ANRS CO20 CUPIC cohort treated with triple therapy were randomly distributed into derivation and validation sets. A total of 52.1% of patients achieved SVR. In the derivation set, a D0 score for the prediction of SVR before treatment initiation included the following independent predictors collected at day 0: prior treatment response, gamma-GT, platelets, telaprevir treatment, viral load. To refine the prediction at the early phase of the treatment, a W4 score included as additional parameter the viral load collected at week 4. The D0 and W4 scores were combined in the CUPIC algorithm defining three subgroups: 'no treatment initiation or early stop at week 4', 'undetermined' and 'SVR highly probable'. In the validation set, the rates of SVR in these three subgroups were, respectively, 11.1%, 50.0% and 82.2% (P < 0.001). By replacing the variable 'prior treatment response' with 'IL28B genotype', another algorithm was derived for treatment-naïve patients with similar results. The CUPIC algorithm is an easy-to-use tool that helps physicians weigh their decision between immediately treating cirrhotic patients using boceprevir/telaprevir triple therapy or waiting for new drugs to become available in their country.
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Affiliation(s)
- J Boursier
- Department of Hepatology and Gastroenterology, CHU d'Angers, Angers, France.,HIFIH, UPRES 3859, SFR 4208, Université LUNAM, Angers, France
| | - A Ducancelle
- HIFIH, UPRES 3859, SFR 4208, Université LUNAM, Angers, France.,Virology Department, CHU d'Angers, Angers, France
| | - J Vergniol
- Department of Hepatology and Gastroenterology, Hôpital Haut-Lévêque, CHU de Bordeaux, Pessac, France
| | - P Veillon
- Department of Hepatology and Gastroenterology, CHU d'Angers, Angers, France.,HIFIH, UPRES 3859, SFR 4208, Université LUNAM, Angers, France.,Virology Department, CHU d'Angers, Angers, France
| | - V Moal
- HIFIH, UPRES 3859, SFR 4208, Université LUNAM, Angers, France.,Biochemistry Department, CHU d'Angers, Angers, France
| | - C Dufour
- Inserm UMR-S1136, Université Pierre-et-Marie-Curie Paris 6, Paris, France
| | - J-P Bronowicki
- Department of Hepatology and Gastroenterology, CHU de Nancy, Université de Lorraine, Inserm U954, Vandoeuvre-lès-Nancy, France
| | - D Larrey
- Liver Unit-IRB-INSERM1040, Hôpital Saint Eloi, CHU de Montpellier, Montpellier, France
| | - C Hézode
- Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, AP-HP, Université Paris-Est, INSERM U955, Créteil, France
| | - F Zoulim
- Department of Hepatology, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, INSERM U1052, Lyon, France
| | - H Fontaine
- Department of Hepatology, Hôpital Cochin, AP-HP, Université Paris-René Descartes, Inserm U1016, Paris, France
| | - V Canva
- Department of Hepatology and Gastroenterology, Centre Hospitalier Régional et Universitaire Claude Huriez, Lille, France
| | - T Poynard
- Department of Hepatology and Gastroenterology, Groupe Hospitalier Pitié-Salpétrière AP-HP, Université Pierre et Marie Curie Paris 6, INSERM UMR-S938, Paris, France
| | - S Allam
- Unit for Basic and Clinical Research on Viral Hepatitis, ANRS (France REcherche Nord & sud Sida-HIV Hépatites-FRENSH), Paris, France
| | - V De Lédinghen
- Department of Hepatology and Gastroenterology, Hôpital Haut-Lévêque, CHU de Bordeaux, Pessac, France.,INSERM U1053, Université Bordeaux Segalen, Bordeaux, France
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10
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Costilla V, Mathur N, Gutierrez JA. Mechanisms of Virologic Failure with Direct-Acting Antivirals in Hepatitis C and Strategies for Retreatment. Clin Liver Dis 2015; 19:641-56, vi. [PMID: 26466653 DOI: 10.1016/j.cld.2015.06.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The current standard of care for hepatitis C therapy is the combination of direct-acting antiviral (DAA) agents. These orally administered medications target the viral proteins and halt the hepatitis C virus lifecycle. Despite high cure rates with these novel drugs, virologic failure with DAAs are of mounting concern as real-world sustained virologic response 12 rates seem lower than expected. The mechanisms of virologic failure to DAAs are likely multifactorial, including baseline resistance variants, the efficacy of the agents used, and host factors. Salvage therapy for DAA virologic failures is an area of emerging research.
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Affiliation(s)
- Vanessa Costilla
- Department of Hepatology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
| | - Neha Mathur
- Department of Hepatology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
| | - Julio A Gutierrez
- Department of Hepatology, The Texas Liver Institute, University of Texas Health Science Center at San Antonio, 607 Camden, San Antonio, TX 78215, USA.
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11
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Salmon D, Bani-Sadr F, Gilbert C, Rosenthal E, Valantin MA, Simon A, Neau D, Morlat P, Loko MA, Wittkop L, Dabis F. HCV viral load at baseline and at week 4 of telaprevir/boceprevir based triple therapies are associated with virological outcome in HIV/hepatitis C co-infected patients. J Clin Virol 2015; 73:32-35. [PMID: 26528903 DOI: 10.1016/j.jcv.2015.10.010] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2015] [Revised: 10/14/2015] [Accepted: 10/16/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND As first generation HCV-specific protease inhibitors, boceprevir (BOC) or telaprevir (TVR) can achieve 60% to 70% sustained virological response (SVR) for HCV infected patients with genotype 1 infections, they could remain temporary a therapeutic option in patients living in resources limited countries with limited access to the new anti-HCV direct acting antiviral (DAA) drugs, such as sofosbuvir. OBJECTIVES AND STUDY DESIGN Here we evaluated in a routine practice setting, the treatment responses, tolerance and factors associated with SVR of a triple therapy with BOC or TVR, combined with pegylated interferon and ribavirin (PegIFN/RBV) in HIV/HCV co-infected patients, included in a large cohort of HIV/HCV coinfected patients (ANRS CO13-HEPAVIH). RESULTS Among the 89 HIV/HCV coinfected patients treated, 65% of whom were previous non-responders to PegIFN/RBV therapy, 65%, 55% and 41% had at baseline genotype 1a, a high baseline HCV-RNA (≥800,000 IU/ml) and a cirrhosis, respectively. The SVR12 rate was 63% overall, 53% for BOC-based regimen and 66% for TVR-based regimen. In multivariate analysis, two factors were significantly associated with HCV SVR: HCV viral load <800,000 IU/mL at treatment initiation versus ≥800,000 IU/mL (OR 4.403, 95% CI 1.29-15.04; p=0.018) and virological response at W4 (HCV-RNA undetectable after 4 weeks of triple therapy) (OR 3.35, 95% CI 1.07-10.48; p=0.038). CONCLUSIONS Overall SVR12 was 63% and our results suggest that HIV/HCV coinfected patients with low HCV viral load (<800,000 IU/mL) and undetectable HCV-RNA after 4 weeks of triple therapy with TVR or BOC-based regimen have a higher probability of treatment success.
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Affiliation(s)
- D Salmon
- Service des Maladies Infectieuses et Tropicales, Hôpital Cochin, APHP-Université Paris Descartes, Paris, France
| | - F Bani-Sadr
- Service des Maladies Infectieuses et Tropicales, CHU Reims, Université Champagne Ardenne, Reims, France.
| | - C Gilbert
- INSERM, ISPED, Center INSERM U897-Epidémiologie-Biostatistiques, F-33000 Bordeaux, France
| | - E Rosenthal
- Service de Médecine Interne, Hôpital de l'Archet, Nice, France
| | - M A Valantin
- Service des Maladies Infectieuses et Tropicales, Hôpital Pitié Salpêtrière-APHP, Paris, France
| | - A Simon
- Service de Médecine Interne, Hôpital Pitié Salpêtrière-APHP, Paris, France
| | - D Neau
- Service des Maladies Infectieuses et Tropicales, Hôpital Pellegrin, Bordeaux, France
| | - P Morlat
- Service de Médecine Interne et Maladies Infectieuses, CHU de Bordeaux, Bordeaux, France
| | - M A Loko
- INSERM, ISPED, Center INSERM U897-Epidémiologie-Biostatistiques, F-33000 Bordeaux, France
| | - L Wittkop
- INSERM, ISPED, Center INSERM U897-Epidémiologie-Biostatistiques, F-33000 Bordeaux, France
| | - F Dabis
- INSERM, ISPED, Center INSERM U897-Epidémiologie-Biostatistiques, F-33000 Bordeaux, France
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12
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Lepida A, Colombo M, Fernandez I, Abdurakhmanov D, Abrao Ferreira P, Strasser SI, Urbanek P, Mangia A, Calleja JL, Iraqi W, DeMasi R, Lonjon-Domanec I, Moreno C, Wedemeyer H. Final Results of the Telaprevir Access Program: FibroScan Values Predict Safety and Efficacy in Hepatitis C Patients with Advanced Fibrosis or Cirrhosis. PLoS One 2015; 10:e0138503. [PMID: 26398503 PMCID: PMC4580464 DOI: 10.1371/journal.pone.0138503] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2015] [Accepted: 08/29/2015] [Indexed: 12/12/2022] Open
Abstract
Background Liver stiffness determined by transient elastography is correlated with hepatic fibrosis stage and has high accuracy for detecting severe fibrosis and cirrhosis in chronic hepatitis C patients. We evaluated the clinical value of baseline FibroScan values for the prediction of safety and efficacy of telaprevir-based therapy in patients with advanced fibrosis and cirrhosis in the telaprevir Early Access Program HEP3002. Methods 1,772 patients with HCV-1 and bridging fibrosis or cirrhosis were treated with telaprevir plus pegylated interferon-α and ribavirin (PR) for 12 weeks followed by PR alone, the total treatment duration depending on virological response and previous response type. Liver fibrosis stage was determined either by liver biopsy or by non-invasive markers. 1,282 patients (72%) had disease stage assessed by FibroScan; among those 46% were classified as Metavir F3 at baseline and 54% as F4. Results Overall, 1,139 patients (64%) achieved a sustained virological response (SVR) by intention-to-treat analysis. Baseline FibroScan values were tested for association with SVR and the occurrence of adverse events. By univariate analysis, higher baseline FibroScan values were predictive of lower sustained virological response rates and treatment-related anemia. By multivariate analysis, FibroScan was no longer statistically significant as an independent predictor, but higher FibroScan values were correlated with the occurrence of infections and serious adverse events. Conclusions FibroScan has a limited utility as a predictor of safety and efficacy in patients treated with telaprevir-based triple therapy. Nevertheless it can be used in association with other clinical and biological parameters to help determine patients who will benefit from the triple regiments. Trial Registration ClinicalTrials.gov NCT01508286
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Affiliation(s)
- Antonia Lepida
- Liver Unit, Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - Massimo Colombo
- Department of Medicine, Division of Gastroenterology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Universita’ degli Studi di Milano, Milan, Italy
| | - Inmaculada Fernandez
- Hospital Universitario 12 de Octubre, Sección de Aparato Digestivo, Madrid, Spain
| | - Djamal Abdurakhmanov
- I.M. Sechenov First Moscow State Medical University, E.M. Tareev Clinic for Nephrology, Internal and Occupational Medicine, Moscow, Russia
| | - Paulo Abrao Ferreira
- Outpatient Clinic to HIV and Viral Hepatitis Division of Infectious Disease, Federal University of São Paulo, São Paulo, Brazil
| | - Simone I. Strasser
- AW Morrow Gastroenterology and Liver Center, Royal Prince Alfred hospital and University of Sydney, Sydney, Australia
| | - Petr Urbanek
- Department of Internal Medicine, First Medical Faculty, Charles University, and Central Military Hospital Prague, Prague, Czech Republic
| | - Alessandra Mangia
- Liver Unit, IRCCS Hospital 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Italy
| | - José L. Calleja
- Gastroenterology, Hospital Universitario Puerta de Hierro, Universidad Autonoma de Madrid, CIBERehd, Madrid, Spain
| | | | - Ralph DeMasi
- Janssen Research and development, Titusville, New Jersey, United States of America
| | | | - Christophe Moreno
- Liver Unit, Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
- * E-mail:
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13
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Salmerón J, Vinaixa C, Berenguer R, Pascasio JM, Sánchez Ruano JJ, Serra M&A, Gila A, Diago M, Romero-Gómez M, Navarro JM, Testillano M, Fernández C, Espinosa D, Carmona I, Pons JA, Jorquera F, Rodriguez FJ, Pérez R, Montero JL, Granados R, Fernández M, Martín AB, Muñoz de Rueda P, Quiles R. Effectiveness and safety of first-generation protease inhibitors in clinical practice: Hepatitis C virus patients with advanced fibrosis. World J Gastroenterol 2015; 21:9163-74. [PMID: 26290644 PMCID: PMC4533049 DOI: 10.3748/wjg.v21.i30.9163] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2015] [Revised: 04/29/2015] [Accepted: 06/26/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluates the effectiveness and safety of the first generation, NS3/4A protease inhibitors (PIs) in clinical practice against chronic C virus, especially in patients with advanced fibrosis.
METHODS: Prospective study and non-experimental analysis of a multicentre cohort of 38 Spanish hospitals that includes patients with chronic hepatitis C genotype 1, treatment-naïve (TN) or treatment-experienced (TE), who underwent triple therapy with the first generation NS3/4A protease inhibitors, boceprevir (BOC) and telaprevir (TVR), in combination with pegylated interferon and ribavirin. The patients were treatment in routine practice settings. Data on the study population and on adverse clinical and virologic effects were compiled during the treatment period and during follow up.
RESULTS: One thousand and fifty seven patients were included, 405 (38%) were treated with BOC and 652 (62%) with TVR. Of this total, 30% (n = 319) were TN and the remaining were TE: 28% (n = 298) relapsers, 12% (n = 123) partial responders (PR), 25% (n = 260) null-responders (NR) and for 5% (n = 57) with prior response unknown. The rate of sustained virologic response (SVR) by intention-to-treatment (ITT) was greater in those treated with TVR (65%) than in those treated with BOC (52%) (P < 0.0001), whereas by modified intention-to-treatment (mITT) no were found significant differences. By degree of fibrosis, 56% of patients were F4 and the highest SVR rates were recorded in the non-F4 patients, both TN and TE. In the analysis by groups, the TN patients treated with TVR by ITT showed a higher SVR (P = 0.005). However, by mITT there were no significant differences between BOC and TVR. In the multivariate analysis by mITT, the significant SVR factors were relapsers, IL28B CC and non-F4; the type of treatment (BOC or TVR) was not significant. The lowest SVR values were presented by the F4-NR patients, treated with BOC (46%) or with TVR (45%). 28% of the patients interrupted the treatment, mainly by non-viral response (51%): this outcome was more frequent in the TE than in the TN patients (57% vs 40%, P = 0.01). With respect to severe haematological disorders, neutropaenia was more likely to affect the patients treated with BOC (33% vs 20%, P≤ 0.0001), and thrombocytopaenia and anaemia, the F4 patients (P = 0.000, P = 0.025, respectively).
CONCLUSION: In a real clinical practice setting with a high proportion of patients with advanced fibrosis, effectiveness of first-generation PIs was high except for NR patients, with similar SVR rates being achieved by BOC and TVR.
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