title: Once-daily simeprevir (TMC435) with pegylated interferon and ribavirin in treatment-naïve genotype 1 hepatitis C: the randomized PILLAR study.
abstract: The phase IIb, double-blind, placebo-controlled PILLAR trial investigated the efficacy and safety of two different simeprevir (SMV) doses administered once-daily (QD) with pegylated interferon (Peg-IFN)-α-2a and ribavirin (RBV) in treatment-naïve patients with HCV genotype 1 infection. Patients were randomized to one of five treatments: SMV (75 or 150 mg QD) for 12 or 24 weeks or placebo, plus Peg-IFN and RBV. Patients in the SMV arms stopped all treatment at week 24 if response-guided therapy (RGT) criteria were met; patients not meeting RGT continued with Peg-IFN and RBV until week 48, as did patients in the placebo control group. Sustained virologic response (SVR) rates measured 24 weeks after the planned end of treatment (SVR24) were 74.7%-86.1% in the SMV groups versus 64.9% in the control group (P < 0.05 for all comparisons [SMV versus placebo], except SMV 75 mg for 24 weeks). Rapid virologic response (HCV RNA <25 IU/mL undetectable at week 4) was achieved by 68.0%-75.6% of SMV-treated and 5.2% of placebo control patients. According to RGT criteria, 79.2%-86.1% of SMV-treated patients completed treatment by week 24; 85.2%-95.6% of these subsequently achieved SVR24. The adverse event profile was generally similar across the SMV and placebo control groups, with the exception of mild reversible hyperbilirubinemia, without serum aminotransferase abnormalities, associated with higher doses of SMV.
  
  
  CONCLUSIONS
  SMV QD in combination with Peg-IFN and RBV significantly improves SVR rates, compared with Peg-IFN and RBV alone, and allows the majority of patients to shorten their therapy duration to 24 weeks.
authors.affiliation: University of North Carolina at Chapel Hill, NC.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Fried
authors.forename: Maria
authors.initials: M
authors.lastname: Buti
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dore
authors.forename: Robert
authors.initials: R
authors.lastname: Flisiak
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
authors.forename: Ira
authors.initials: I
authors.lastname: Jacobson
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.forename: Michael
authors.initials: M
authors.lastname: Manns
authors.forename: Igor
authors.initials: I
authors.lastname: Nikitin
authors.forename: Fred
authors.initials: F
authors.lastname: Poordad
authors.forename: Morris
authors.initials: M
authors.lastname: Sherman
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Jane
authors.initials: J
authors.lastname: Scott
authors.forename: Leen
authors.initials: L
authors.lastname: Gilles
authors.forename: Oliver
authors.initials: O
authors.lastname: Lenz
authors.forename: Monika
authors.initials: M
authors.lastname: Peeters
authors.forename: Vanitha
authors.initials: V
authors.lastname: Sekar
authors.forename: Goedele
authors.initials: G
authors.lastname: De Smedt
authors.forename: Maria
authors.initials: M
authors.lastname: Beumont-Mauviel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006575:Heterocyclic Compounds, 3-Ring / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D000069616:Simeprevir; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D006575:Heterocyclic Compounds, 3-Ring; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D013449:Sulfonamides; D011092:Polyethylene Glycols; D012254:Ribavirin; D000069616:Simeprevir; C100416:peginterferon alfa-2a
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