Original Title: Agentes antivirales directos en el tratamiento de la hepatitis C crónica. Evaluación comparada de eficacia y seguridad

Authors' objectives: To assess the relative efficacy and safety of interferon-free direct acting antivirals (DAA): sofosbuvir plus ribavirin, sofosbuvir plus simeprevir, sofosbuvir plus daclatasvir, sofosbuvir plus ledipasvir, ombitasvir/paritaprevir/ritonavir with or without dasabuvir (with or without ribavirin), for the treatment of naïve and pretreated patients with chronic hepatitis C (CHC) infection (genotypes 1 through 6).

Authors' results and conclusions: The conclusions related to the relative efficacy, in terms of sustained virological response (based on the results of Bayesian Network Metanalysis), are presented according to genotype subtype, previous treatment and cirrhosis status. For patients with genotype 1 hepatitis C virus (HCV) infection: Treatment naïve patients: ­ Without cirrhosis: There are no significant differences among the following regimens: SOF8+LDV8, SOF12+LDV12, DCV12+SOF12, PAR/RIT12+OMB12+DAS12±RBV12 and SIM12+SOF12. ­ With cirrhosis: There are no significant differences between the following regimens: SOF12+LDV12±RBV12, SIM12+SOF12 and PAR/RIT12+OMB12+DAS12+RBV12. ­ There is no evidence available to allow analysis of efficacy for the regimen DCV24 + SOF24. Previously treated patients: ­ Without cirrhosis: PAR/RIT12+OMB12+DAS12+RBV12 significantly improves SVR rates over SOF12+LDV12. Moreover PAR/RIT12+OMB12+DAS12+RBV12 significantly improves SVR rates over SIM12+SOF12. ­ With cirrhosis: There are no significant differences between the following regimens: PAR/RIT12+OMB12+DAS12+RBV12, SOF12+LDV12±RBV12, SOF24+LDV24 and SIM12+SOF12. ­ There is no evidence available to allow analysis of efficacy for the regimen DCV+ SOF12/24. - Data for the efficacy of treatments for CHC infection in patients previously treated unsuccessfully with DAA+PEG RBV regimens are limited. The regimens SOF12+ PR12, SOF + LDV ± RBV and SOF24 + RBV24 report high SVR rates. For patients with genotype 2 HCV infection: Treatment naïve patients: ­ There are no significant differences between the regimens SOF12+RBV12 and SOF12+ PEG RBV12. Previously treated patients ­ Without cirrhosis: There are no significant differences between the regimens SOF12+RBV12 and SOF12+ PEG RBV12. ­ With cirrhosis: There are no significant differences between the regimens SOF16+RBV16 and SOF12+RBV12. For patients with genotype 3 HCV infection: Treatment naive patients: ­ Without cirrhosis: There are no significant differences between the regimens SOF24+RBV24 and DCV12+SOF12. ­ With cirrhosis: There are no significant differences between the regimens SOF12+PEG RBV12 and SOF24+RBV24. ­ There is no evidence available to allow analysis of efficacy for the regimens SOF12+PEG RBV12 and DCV24+SOF24±RBV24. Previously treated patients: ­ Without cirrhosis: There are no significant differences between the regimens SOF24+RBV24 and DCV12+SOF12. ­ With cirrhosis: There are no significant differences between the regimens SOF12+PEG RBV12 and SOF24+RBV24. ­ There is no evidence available to allow analysis of efficacy for the regimen DCV24+SOF24±RBV24. For patients with genotype 4 HCV infection: Treatment naive patients: ­ Without cirrhosis: There are no significant differences between the regimens: SOF24+RBV24, SOF12+RVB12 and PAR/RIT12+OMB12+RBV12. ­ With cirrhosis: There are no significant differences between the regimens: SOF24+RBV24 and SOF12+RVB12. ­ There is no evidence available to allow analysis of efficacy for the regimen SOF12+LDV12. ­ The regimen SIM12+SOF12 was not considered. Previously treated patients: ­ Without cirrhosis: Neither SOF12+RVB12 nor PAR/RIT12+OMB12+RBV12 are significantly different from SOF24+RBV24. ­ With cirrhosis: There are no significant differences between the regimens: SOF24+RBV24 and SOF12+RVB12. ­ There is no evidence available to allow analysis of efficacy for the regimen SOF12+LDV12. ­ The regimen SIM12+SOF12 was not considered. The data for genotype 5 and 6 HCV infections were insufficient for meta-analysis. The conclusions related to the relative safety, in terms of rash, anemia and depression (based on the results of Bayesian Network Metanalysis) are presented according to previous treatment. Regarding rash: ­ Treatment naive patients: The regimens SOF12+LDV12 and PAR/RIT12+OMB12+DAS12 are associated with significantly lower risks compared to PAR/RIT12+OMB12+DAS12+RBV12. ­ Previously treated patients: The regimen PAR/RIT12+OMB12+DAS12 is associated with significantly lower risk compared to PAR/RIT12+OMB12+DAS12+RBV12. Regarding anemia: ­ Treatment naive patients: The regimen SOF12+LDV12 is associated with significantly lower risk compared to PAR/RIT12+OMB12+DAS12±RBV12. ­ Previously treated patients: The regimens SOF12+LDV12 and PAR/RIT12+OMB12+DAS12 are associated with significantly lower risks compared to PAR/RIT12+OMB12+DAS12+RBV12. Regarding depression: ­ Treatment naive patients: The regimen SOF12+LDV12 is associated with significantly lower risk compared to DCV12+SOF12. ­ Previously treated patients: There are no significant differences between the regimens SOF24+RBV24 and PAR/RIT12+OMB12+DAS12+RBV12.

Authors' methods: First of all, the national and international agencies and institutes of Health Technology Assessment (HTA) were consulted (4th of February 2016) in order to find HTA reports. The search was also conducted in the International Network of Agencies for HTA (INAHTA) and Centre for Reviews and Dissemination (CRD) web sites. The study eligibility criteria were: - Population: Adult patients with confirmed CHC infection (genotypes 1 through 6). - Interventions: direct acting antiviral with or without ribavirin authorized in Europe before December 2015. - Comparators: direct acting antiviral with or without ribavirin. - Outcomes: efficacy [sustained virological response (SVR)] and safety (adverse events). - Study design: health technology assessment reports.

Project Status: Completed

Year Published: 2017

URL for published report: https://www.aetsa.org/publicacion/agentes-antivirales-directos-en-el-tratamiento-de-la-hepatitis-c-cronica-evaluacion-comparada-de-eficacia-y-seguridad/

English language abstract: An English language summary is available

Publication Type: Mini HTA

Country: Spain

Organisation Name: Andalusian Health Technology Assessment Area

Contact Address: Area de Evaluacion de Tecnologias Sanitarias Sanitarias de Andalucia (AETSA) Avda. Innovación, s/n Edificio Arena 1. Sevilla (Spain) Tel. +34 955 006 309

Contact Name: aetsa.csalud@juntadeandalucia.es

Contact Email: aetsa.csalud@juntadeandalucia.es

Copyright: Andalusian Health Technology Assessment Area