Boceprevir is highly effective in treatment-experienced hepatitis C virus-positive genotype-1 menopausal women.

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.

• Authors: 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
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 20 Issue 44 Pg. 16726-33 (Nov 28 2014) ISSN: 2219-2840 [Electronic] United States
• PMID: 25469044 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Biomarkers
• Interferon alpha-2
• Interferon-alpha
• RNA, Viral
• Recombinant Proteins
• Polyethylene Glycols
• Ribavirin
• 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
• Proline
• peginterferon alfa-2b

Topics

• Antiviral Agents (adverse effects, therapeutic use)
• Biomarkers (blood)
• Drug Therapy, Combination
• Female
• Genotype
• Hepacivirus (drug effects, genetics, pathogenicity)
• Hepatitis C, Chronic (blood, diagnosis, drug therapy, virology)
• Humans
• Interferon alpha-2
• Interferon-alpha (therapeutic use)
• Italy
• Logistic Models
• Menopause
• Middle Aged
• Multivariate Analysis
• Odds Ratio
• Polyethylene Glycols (therapeutic use)
• Proline (adverse effects, analogs & derivatives, therapeutic use)
• RNA, Viral (blood)
• Recombinant Proteins (therapeutic use)
• Ribavirin (therapeutic use)
• Time Factors
• Treatment Outcome
• Viral Load