title: Clinical and virological predictors of sustained response with an interferon-based simeprevir regimen for patients with chronic genotype 1 hepatitis C virus infection.
abstract: Simeprevir plus peg-interferon/ribavirin (PR) is approved to treat chronic hepatitis C (HCV) genotype 1 (GT1) and GT4 infection. This study aimed to assess baseline and on-treatment the factors predictive of sustained virologic response 12-weeks post-treatment (SVR12) in patients receiving 12 weeks of simeprevir plus PR followed by 12 or 36 weeks of PR. Data from participants in four studies (QUEST-1, QUEST-2, ATTAIN and PROMISE) were pooled to examine the efficacy and safety of simeprevir+PR in HCV GT1 patients. The predictive power of baseline variables for SVR12 was assessed using univariate and multivariate logistic regression models while the relationship between early (Week 4) on-treatment response and SVR12 was analyzed by GT1 subtype and treatment experience. Data for 1160 patients were analyzed (overall SVR12: 71%). Baseline factors predictive of SVR12 were: IL28B CC genotype, GT1a/Q80K-negative, treatment-naïve/prior relapser, no cirrhosis, HCV-RNA ≤2,000,000IU/mL, albumin >42g/L, platelets >200x109 /L. Patients with HCV GT1b (86%), IL28B CC genotype (87%), and treatment-naïve patients (83%) were predicted to achieve the highest SVR12 rates and rates of rapid virologic response. Week 4 early on-treatment response identified treatment-naïve and prior relapse patients likely to achieve SVR12. Patients likely to respond to simeprevir+PR can be identified using baseline factors. Early on-treatment response predicts treatment success.
authors.affiliation: National Institute for Infectious Diseases "L. Spallanzani" I.R.C.C.S, 292 Via Portuense, 00149 Rome, Italy.
authors.forename: Gianpiero
authors.initials: G
authors.lastname: D'Offizi
authors.affiliation: Section of Gastroenterology, Di.Bi.M.I.S., University of Palermo, Piazza Marina 61, 90133, Italy.
authors.forename: Calogero
authors.initials: C
authors.lastname: Cammà
authors.affiliation: National Institute for Infectious Diseases "L. Spallanzani" I.R.C.C.S, 292 Via Portuense, 00149 Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Taibi
authors.affiliation: Janssen-Cilag Pharma GmbH, Vorgartenstraße 206B, 1020 Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Schlag
authors.affiliation: Janssen-Cilag Pharma GmbH, Vorgartenstraße 206B, 1020 Vienna, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Weber
authors.affiliation: Janssen-Cilag, Via Michelangelo Buonarroti 23, 20093 Cologno Monzese, Milan, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Palma
authors.affiliation: Janssen Research & Development LLC, Trenton Harbourton Road, Titusville, NJ 08560, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: DeMasi
authors.affiliation: Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Janssen
authors.affiliation: Janssen Research & Development LLC, Trenton Harbourton Road, Titusville, NJ 08560, USA.
authors.forename: James
authors.initials: J
authors.lastname: Witek
authors.affiliation: National Institute for Infectious Diseases "L. Spallanzani" I.R.C.C.S, 292 Via Portuense, 00149 Rome, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Lionetti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000418:Albumins; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D007372:Interferons / Q000008:administration & dosage / Q000627:therapeutic use*; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral; D012008:Recurrence; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D000069616:Simeprevir / Q000008:administration & dosage / Q000627:therapeutic use*; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000418:Albumins; D007372:Interferons; D007378:Interleukins; D012367:RNA, Viral; D012254:Ribavirin; D000069616:Simeprevir; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: Genotype 1; Hepatitis C; Interferon-based therapy; Simeprevir