title: Boceprevir is highly effective in treatment-experienced hepatitis C virus-positive genotype-1 menopausal women.
abstract: OBJECTIVE
  To investigate the safety/efficacy of Boceprevir-based triple therapy in hepatitis C virus (HCV)-G1 menopausal women who were historic relapsers, partial-responders and null-responders.
  
  
  METHODS
  In this single-assignment, unblinded study, we treated fifty-six menopausal women with HCV-G1, 46% F3-F4, and previous PEG-α/RBV failure (7% null, 41% non-responder, and 52% relapser) with 4 wk lead-in with PEG-IFNα2b/RBV followed by PEG-IFNα2b/RBV+Boceprevir for 32 wk, with an additional 12 wk of PEG-IFN-α-2b/RBV if patients were HCV-RNA-positive by week 8. In previous null-responders, 44 wk of triple therapy was used. The primary objective of retreatment was to verify whether a sustained virological response (SVR) (HCV RNA undetectable at 24 wk of follow-up) rate of at least 20% could be obtained. The secondary objective was the evaluation of the percent of patients with negative HCV RNA at week 4 (RVR), 8 (RVR BOC), 12 (EVR), or at the end-of-treatment (ETR) that reached SVR. To assess the relationship between SVR and clinical and biochemical parameters, multiple logistic regression analysis was used.
  
  
  RESULTS
  After lead-in, only two patients had RVR; HCV-RNA was unchanged in all but 62% who had ≤ 1 log10 decrease. After Boceprevir, HCV RNA became undetectable at week 8 in 32/56 (57.1%) and at week 12 in 41/56 (73.2%). Of these, 53.8% and 52.0%, respectively, achieved SVR. Overall, SVR was obtained in 25/56 (44.6%). SVR was achieved in 55% previous relapsers vs. 41% non-responders (P = 0.250), in 44% F0-F2 vs 54% F3-F4 (P = 0.488), and in 11/19 (57.9%) of patients with cirrhosis. At univariate analysis for baseline predictors of SVR, only previous response to antiviral therapy (OR = 2.662, 95%CI: 0.957-6.881, P = 0.043), was related with SVR. When considering "on treatment" factors, 1 log10 HCV RNA decline at week 4 (3.733, 95%CI: 1.676-12.658, P = 0.034) and achievement of RVR BOC (7.347, 95%CI: 2.156-25.035, P = 0.001) were significantly related with the SVR, although RVR BOC only (6.794, 95%CI: 1.596-21.644, P = 0.010) maintained significance at multivariate logistic regression analysis. Anemia and neutropenia were managed with Erythropoietin and Filgrastim supplementation, respectively. Only six patients discontinued therapy.
  
  
  CONCLUSIONS
  Boceprevir obtained high SVR response independent of previous response, RVR or baseline fibrosis or cirrhosis. RVR BOC was the only independent predictor of SVR.
authors.affiliation: Veronica Bernabucci, Aimilia Karampatou, Laura Turco, Rosina Critelli, Paola Todesca, Caterina Cerami, Erica Villa, Division of Gastroenterology, Azienda Ospedaliero-Universitaria Policlinico di Modena, Italy Università degli Studi di Modena e Reggio Emilia, 41124 Modena, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Bernabucci
authors.affiliation: Veronica Bernabucci, Aimilia Karampatou, Laura Turco, Rosina Critelli, Paola Todesca, Caterina Cerami, Erica Villa, Division of Gastroenterology, Azienda Ospedaliero-Universitaria Policlinico di Modena, Italy Università degli Studi di Modena e Reggio Emilia, 41124 Modena, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Ciancio
authors.affiliation: Veronica Bernabucci, Aimilia Karampatou, Laura Turco, Rosina Critelli, Paola Todesca, Caterina Cerami, Erica Villa, Division of Gastroenterology, Azienda Ospedaliero-Universitaria Policlinico di Modena, Italy Università degli Studi di Modena e Reggio Emilia, 41124 Modena, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Petta
authors.affiliation: Veronica Bernabucci, Aimilia Karampatou, Laura Turco, Rosina Critelli, Paola Todesca, Caterina Cerami, Erica Villa, Division of Gastroenterology, Azienda Ospedaliero-Universitaria Policlinico di Modena, Italy Università degli Studi di Modena e Reggio Emilia, 41124 Modena, Italy.
authors.forename: Aimilia
authors.initials: A
authors.lastname: Karampatou
authors.affiliation: Veronica Bernabucci, Aimilia Karampatou, Laura Turco, Rosina Critelli, Paola Todesca, Caterina Cerami, Erica Villa, Division of Gastroenterology, Azienda Ospedaliero-Universitaria Policlinico di Modena, Italy Università degli Studi di Modena e Reggio Emilia, 41124 Modena, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Turco
authors.affiliation: Veronica Bernabucci, Aimilia Karampatou, Laura Turco, Rosina Critelli, Paola Todesca, Caterina Cerami, Erica Villa, Division of Gastroenterology, Azienda Ospedaliero-Universitaria Policlinico di Modena, Italy Università degli Studi di Modena e Reggio Emilia, 41124 Modena, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Strona
authors.affiliation: Veronica Bernabucci, Aimilia Karampatou, Laura Turco, Rosina Critelli, Paola Todesca, Caterina Cerami, Erica Villa, Division of Gastroenterology, Azienda Ospedaliero-Universitaria Policlinico di Modena, Italy Università degli Studi di Modena e Reggio Emilia, 41124 Modena, Italy.
authors.forename: Rosina
authors.initials: R
authors.lastname: Critelli
authors.affiliation: Veronica Bernabucci, Aimilia Karampatou, Laura Turco, Rosina Critelli, Paola Todesca, Caterina Cerami, Erica Villa, Division of Gastroenterology, Azienda Ospedaliero-Universitaria Policlinico di Modena, Italy Università degli Studi di Modena e Reggio Emilia, 41124 Modena, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Todesca
authors.affiliation: Veronica Bernabucci, Aimilia Karampatou, Laura Turco, Rosina Critelli, Paola Todesca, Caterina Cerami, Erica Villa, Division of Gastroenterology, Azienda Ospedaliero-Universitaria Policlinico di Modena, Italy Università degli Studi di Modena e Reggio Emilia, 41124 Modena, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Cerami
authors.affiliation: Veronica Bernabucci, Aimilia Karampatou, Laura Turco, Rosina Critelli, Paola Todesca, Caterina Cerami, Erica Villa, Division of Gastroenterology, Azienda Ospedaliero-Universitaria Policlinico di Modena, Italy Università degli Studi di Modena e Reggio Emilia, 41124 Modena, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Sagnelli
authors.affiliation: Veronica Bernabucci, Aimilia Karampatou, Laura Turco, Rosina Critelli, Paola Todesca, Caterina Cerami, Erica Villa, Division of Gastroenterology, Azienda Ospedaliero-Universitaria Policlinico di Modena, Italy Università degli Studi di Modena e Reggio Emilia, 41124 Modena, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Rizzetto
authors.affiliation: Veronica Bernabucci, Aimilia Karampatou, Laura Turco, Rosina Critelli, Paola Todesca, Caterina Cerami, Erica Villa, Division of Gastroenterology, Azienda Ospedaliero-Universitaria Policlinico di Modena, Italy Università degli Studi di Modena e Reggio Emilia, 41124 Modena, Italy.
authors.forename: Calogero
authors.initials: C
authors.lastname: Cammà
authors.affiliation: Veronica Bernabucci, Aimilia Karampatou, Laura Turco, Rosina Critelli, Paola Todesca, Caterina Cerami, Erica Villa, Division of Gastroenterology, Azienda Ospedaliero-Universitaria Policlinico di Modena, Italy Università degli Studi di Modena e Reggio Emilia, 41124 Modena, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Villa
mesh_terms: D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007558:Italy; D016015:Logistic Models; D008593:Menopause; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011392:Proline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; 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; C417083:peginterferon alfa-2b
keywords: Genotype 1; Hepatitis C virus treatment; Menopause; Pegylated Interferon; Viral Hepatitis