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Lower response to simeprevir and sofosbuvir in HCV genotype 1 in routine practice compared with clinical trials

BACKGROUND: High sustained virological response at 12 weeks after end of treatment (SVR12) with 12 weeks of simeprevir and sofosbuvir±ribavirin (SMV+SOF±RBV) has been demonstrated in hepatitis C virus genotype 1 (HCV-1) but is based on limited data. Therefore, we performed a meta-analysis of availab...

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Autores principales: Yee, Brittany E, Nguyen, Nghia H, Jin, Minjuan, Lutchman, Glen, Lim, Joseph K, Nguyen, Mindie H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4780041/
https://www.ncbi.nlm.nih.gov/pubmed/26966547
http://dx.doi.org/10.1136/bmjgast-2015-000056
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author Yee, Brittany E
Nguyen, Nghia H
Jin, Minjuan
Lutchman, Glen
Lim, Joseph K
Nguyen, Mindie H
author_facet Yee, Brittany E
Nguyen, Nghia H
Jin, Minjuan
Lutchman, Glen
Lim, Joseph K
Nguyen, Mindie H
author_sort Yee, Brittany E
collection PubMed
description BACKGROUND: High sustained virological response at 12 weeks after end of treatment (SVR12) with 12 weeks of simeprevir and sofosbuvir±ribavirin (SMV+SOF±RBV) has been demonstrated in hepatitis C virus genotype 1 (HCV-1) but is based on limited data. Therefore, we performed a meta-analysis of available data evaluating the effectiveness of SMV+SOF±RBV in HCV-1. METHODS: We performed a comprehensive literature search in June 2015 to identify randomised controlled trials (RCTs) and observational studies of HCV-1 patients treated with 12 weeks of SMV+SOF±RBV. Original studies with SVR12 data in ≥5 HCV-1 patients were included. We excluded studies on liver transplant recipients and/or patients co-infected with HIV or hepatitis B/D. We estimated pooled effect sizes using a random-effects model and evaluated heterogeneity with Cochrane Q-test, p≤0.10 and I(2) statistic ≥50%. RESULTS: Pooled SVR12 was 85.6% (CI 81.3% to 89.0%) in 1389 HCV-1 patients from 15 studies. On subgroup analysis, SVR12 was 83.9% (CI 79.4% to 87.5%) in observational studies, which was lower than 93.5% (CI 85.7% to 97.2%) in RCTs. A trend showed SVR12 was higher in mild fibrosis, 93.0% (CI 86.2% to 96.6%) compared with advanced fibrosis, 81.5% (CI 75.7% to 86.1%), OR 2.22 (CI 0.79 to 6.25, p=0.131). There was no significant difference in SVR12 rates between HCV-1a, 89.9% (CI 81.9% to 94.6%) and HCV-1b, 89.0% (CI 78.9% to 94.6%) with OR 1.35 (CI 0.75 to 2.42, p=0.322). The most common pooled side effects were: headache 15.2% (n=55/361), fatigue 12.1% (n=78/646), nausea 9.5% (n=50/527) and rash 9.3% (n=68/728). CONCLUSIONS: SMV+SOF±RBV is an effective regimen in HCV-1 patients. The SVR12 rate in observational studies was lower than that in RCTs, which may reflect the more diverse patient population in real-world settings.
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spelling pubmed-47800412016-03-10 Lower response to simeprevir and sofosbuvir in HCV genotype 1 in routine practice compared with clinical trials Yee, Brittany E Nguyen, Nghia H Jin, Minjuan Lutchman, Glen Lim, Joseph K Nguyen, Mindie H BMJ Open Gastroenterol Meta Analysis BACKGROUND: High sustained virological response at 12 weeks after end of treatment (SVR12) with 12 weeks of simeprevir and sofosbuvir±ribavirin (SMV+SOF±RBV) has been demonstrated in hepatitis C virus genotype 1 (HCV-1) but is based on limited data. Therefore, we performed a meta-analysis of available data evaluating the effectiveness of SMV+SOF±RBV in HCV-1. METHODS: We performed a comprehensive literature search in June 2015 to identify randomised controlled trials (RCTs) and observational studies of HCV-1 patients treated with 12 weeks of SMV+SOF±RBV. Original studies with SVR12 data in ≥5 HCV-1 patients were included. We excluded studies on liver transplant recipients and/or patients co-infected with HIV or hepatitis B/D. We estimated pooled effect sizes using a random-effects model and evaluated heterogeneity with Cochrane Q-test, p≤0.10 and I(2) statistic ≥50%. RESULTS: Pooled SVR12 was 85.6% (CI 81.3% to 89.0%) in 1389 HCV-1 patients from 15 studies. On subgroup analysis, SVR12 was 83.9% (CI 79.4% to 87.5%) in observational studies, which was lower than 93.5% (CI 85.7% to 97.2%) in RCTs. A trend showed SVR12 was higher in mild fibrosis, 93.0% (CI 86.2% to 96.6%) compared with advanced fibrosis, 81.5% (CI 75.7% to 86.1%), OR 2.22 (CI 0.79 to 6.25, p=0.131). There was no significant difference in SVR12 rates between HCV-1a, 89.9% (CI 81.9% to 94.6%) and HCV-1b, 89.0% (CI 78.9% to 94.6%) with OR 1.35 (CI 0.75 to 2.42, p=0.322). The most common pooled side effects were: headache 15.2% (n=55/361), fatigue 12.1% (n=78/646), nausea 9.5% (n=50/527) and rash 9.3% (n=68/728). CONCLUSIONS: SMV+SOF±RBV is an effective regimen in HCV-1 patients. The SVR12 rate in observational studies was lower than that in RCTs, which may reflect the more diverse patient population in real-world settings. BMJ Publishing Group 2016-03-02 /pmc/articles/PMC4780041/ /pubmed/26966547 http://dx.doi.org/10.1136/bmjgast-2015-000056 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/ This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
spellingShingle Meta Analysis
Yee, Brittany E
Nguyen, Nghia H
Jin, Minjuan
Lutchman, Glen
Lim, Joseph K
Nguyen, Mindie H
Lower response to simeprevir and sofosbuvir in HCV genotype 1 in routine practice compared with clinical trials
title Lower response to simeprevir and sofosbuvir in HCV genotype 1 in routine practice compared with clinical trials
title_full Lower response to simeprevir and sofosbuvir in HCV genotype 1 in routine practice compared with clinical trials
title_fullStr Lower response to simeprevir and sofosbuvir in HCV genotype 1 in routine practice compared with clinical trials
title_full_unstemmed Lower response to simeprevir and sofosbuvir in HCV genotype 1 in routine practice compared with clinical trials
title_short Lower response to simeprevir and sofosbuvir in HCV genotype 1 in routine practice compared with clinical trials
title_sort lower response to simeprevir and sofosbuvir in hcv genotype 1 in routine practice compared with clinical trials
topic Meta Analysis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4780041/
https://www.ncbi.nlm.nih.gov/pubmed/26966547
http://dx.doi.org/10.1136/bmjgast-2015-000056
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