A network meta-analysis to compare simeprevir with boceprevir and telaprevir in combination with peginterferon-α and ribavirin in patients infected with genotype 1 Hepatitis C virus.
OBJECTIVE
To conduct a network meta-analysis (NMA) to assess the relative efficacy and safety of simeprevir, a second generation oral protease inhibitor (PI), compared to telaprevir and boceprevir in combination with pegylated interferon-α and ribavirin (PR) in patients with chronic hepatitis C.


METHODS
A systematic literature review and NMA of randomized controlled trials involving anti-virals added to PR were conducted. Electronic database searches and hand searches were conducted to identify relevant publications. Outcomes of interest included sustained virologic response (SVR), incidence of adverse events (AEs), and discontinuation due to AEs. Networks were based on treatment-, dose-, and duration-specific nodes. Sub-group analyses were conducted to investigate heterogeneity, based on Metavir scores, sub-genotypes 1a/1b, and prior response.


RESULTS
A total of 15 publications were considered for the base case of the meta-analysis. Simeprevir was associated with higher SVR rates than PR alone. Compared to telaprevir and boceprevir, SVR rates tended to be higher for simeprevir, with odds ratios ranging from 1.27 [0.81-2.00] to 2.61 [1.44-4.74] in treatment-naïve and from 1.04 [0.78-1.38] to 1.74 [0.84-3.61] in treatment-experienced patients, respectively. In terms of safety, the risks of anemia and discontinuations due to AEs were lower for simeprevir compared to PR alone, telaprevir, and boceprevir. The risk of rash was lower for simeprevir compared to telaprevir, and similar compared to PR alone and boceprevir.


CONCLUSIONS
This NMA in genotype 1 HCV patients suggests a similar or better efficacy and tolerability profile for simeprevir compared to telaprevir and boceprevir.
a a Amaris , London , UK.
Vanessa
V
Taieb
b b Amaris , Paris , France.
Maud
M
Pacou
a a Amaris , London , UK.
Sophia
S
Ho
a a Amaris , London , UK.
Ségolène
S
Pettré
c c Janssen EMEA , Beerse , Belgium.
Suzy
S
Van Sanden
c c Janssen EMEA , Beerse , Belgium.
Marta
M
Pisini
d d North Manchester General Hospital , Manchester , UK.
Andrew
A
Ustianowski
e e Janssen-Cilag GmbH , Neuss , Germany.
Angelika
A
Mehnert
D000998:Antiviral Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D016206:Databases, Bibliographic; D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D016898:Interferon-alpha / Q000627:therapeutic use; D009842:Oligopeptides / Q000627:therapeutic use; D011392:Proline / Q000031:analogs & derivatives / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000627:therapeutic use*; D012254:Ribavirin / Q000627:therapeutic use; D000069616:Simeprevir / Q000627:therapeutic use; D019562:Viral Load / Q000187:drug effects
D000998:Antiviral Agents; D007155:Immunologic Factors; D016898:Interferon-alpha; D009842:Oligopeptides; D011480:Protease Inhibitors; D012254:Ribavirin; C486464:telaprevir; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline; D000069616:Simeprevir
Genotype 1; Hepatitis C virus; Network meta-analysis; Protease inhibitors; Simeprevir; Treatment