Clinical Trials Study
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World J Gastroenterol. Nov 28, 2014; 20(44): 16726-16733
Published online Nov 28, 2014. doi: 10.3748/wjg.v20.i44.16726
Boceprevir is highly effective in treatment-experienced hepatitis C virus-positive genotype-1 menopausal women
Veronica Bernabucci, Alessia Ciancio, Salvatore Petta, Aimilia Karampatou, Laura Turco, Silvia Strona, Rosina Critelli, Paola Todesca, Caterina Cerami, Caterina Sagnelli, Mario Rizzetto, Calogero Cammà, Erica Villa
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
Alessia Ciancio, Silvia Strona, Mario Rizzetto, Division of Gastroenterology, University of Turin, 10126 Turin, Italy
Salvatore Petta, Calogero Cammà, Division of Gastroenterology, DiBiMIS, University of Palermo, 90127 Palermo, Italy
Caterina Sagnelli, Dipartimento Medico-Chirurgico di Internistica Clinica e Sperimentale “F. Magrassi-A. Lanzara”, Second University of Naples, 80131 Naples, Italy
Author contributions: Bernabucci V revised the draft and in collaboration with Ciancio A, Turco L, Strona S, Cerami C, Sagnelli C, Karampatou A enrolled patients, collected and analysed the data; Critelli R collected, analysed the data and also revised the draft; Petta S collected, analysed the data, revised statistical analysis and was also involved in revising the draft; Rizzetto M contributed to the design of the study and revised the draft; Cammà C contributed to the design of the study, performed statistical analysis and revised the draft; Villa E designed the study, analysed the data and wrote the paper.
Supported by Schering-Plough (now Merck)
Correspondence to: Erica Villa, Professor, Division of Gastroenterology, Azienda Ospedaliero-Universitaria Policlinico di Modena, Università degli Studi di Modena e Reggio Emilia, via del Pozzo 71, 41124 Modena, Italy. erica.villa@unimore.it
Telephone: +39-59-4225308 Fax: +39-59-4222624
Received: April 25, 2014
Revised: June 19, 2014
Accepted: July 29, 2014
Published online: November 28, 2014
Abstract

AIM: 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.

CONCLUSION: Boceprevir obtained high SVR response independent of previous response, RVR or baseline fibrosis or cirrhosis. RVR BOC was the only independent predictor of SVR.

Keywords: Hepatitis C virus treatment, Pegylated Interferon, Viral Hepatitis, Menopause, Genotype 1

Core tip: After menopause liver disease in hepatitis C virus-positive women becomes rapidly progressive, severe fibrosis develops, and response to antiviral therapy becomes very low. Re-treatment with standard dual therapy in previous failures of Peginterferon-α + Ribavirin (PEG-IFNα/RBV) treatments does not achieve more than 5%-10% sustained virological response (SVR). The addition of Boceprevir to PEG-IFNα/RBV in menopausal women with HCV-1 genotype infection, who had previously failed dual antiviral therapy, determined a striking improvement of SVR. More than 45% of women re-treated with triple therapy achieved SVR, with few side effects and good tolerability. Response after 4 wk of Boceprevir was the only independent factor predicting SVR.