Safety and efficacy of triple therapy with peginterferon, ribavirin and boceprevir within an early access programme in Spanish patients with hepatitis C genotype 1 with severe fibrosis: SVRw12 analysis.

Abstract

BACKGROUND & AIMS:

The addition of protease inhibitors (PIs) changed the hepatitis C virus (HCV) treatment standards and improved sustained viral response (SVR) rates in patients with genotype 1 HCV infection.

METHODS:

Prospective, multicentre, national registry that includes naïve and treatment-experienced patients with HCV genotype 1 infection, who had bridging fibrosis or cirrhosis and were treated with triple therapy (peginterferon alfa-2a or alfa-2b, ribavirin and boceprevir) as compassionate use, and in accordance with the Summary of Product Characteristics.

RESULTS:

Most of the patients (68.2%) were male, with a mean age of 53 years, 75% (n = 128) had HCV 1b genotype and baseline viral load of 6.2 log. According to prior treatment, 20% of patients were treatment-naïve and 80% had received prior treatment. Approximately 36.5% of patients (n = 62) reported at least one serious adverse events (SAEs) (total SAEs = 103). The most common SAEs were neutropenia (57.6%), anaemia (47.6%) and grade 3 thrombopenia (25.9%). Patients with albumin <3.5 g/dl and bilirubin >2 mg/dl had an increased relative risk (greater than one-fold) for SAEs, including infections and hepatic decompensation. In the intent-to-treat analysis (n = 170), the overall percentage of patients with SVRw12 was 46.5%. In patients with 1 log decrease at week 4 (lead-in phase), the overall SVRw12 rate was 67.0%. In the patients initiating triple therapy with boceprevir (n = 139), the global response rate was 56.4%. In a multivariate analysis, an increased probability of achieving SVR was associated with response to prior treatment (relapsers), >1 log decrease in viral load in the lead-in phase and baseline albumin >3.5 g/dl.

CONCLUSIONS:

Triple therapy in patients with severe fibrosis/cirrhosis is associated with a higher rate of SAE and a lower rate in comparison with patients with mild disease. However, for patients with intact liver function, it could be considered as a treatment option, when other alternatives would not be available.

• Authors: Jose L Calleja, Juan M Pascasio, Belén Ruiz-Antorán, Francisco Gea, Rafael Bárcena, Juan R Larrubia, Ramón Pérez-Álvarez, Jose M Sousa, Manuel Romero-Gómez, Ricard Solá, Juan de la Revilla, Javier Crespo, Jose M Navarro, Juan I Arenas, Manuel Delgado, Conrado M Fernández-Rodríguez, Ramon Planas, Maria Buti, Xavier Forns, Spanish Group for the Study of the Use of Direct-Acting Drugs Hepatitis C with Severe Fibrosis
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 35 Issue 1 Pg. 90-100 (Jan 2015) ISSN: 1478-3231 [Electronic] United States
• PMID: 25113158 (Publication Type: Clinical Trial, Journal Article, Multicenter Study)
• Copyright: © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Interferon-alpha
• Protease Inhibitors
• 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-2a

Topics

• Compassionate Use Trials
• Drug Therapy, Combination (adverse effects)
• Hepacivirus (genetics)
• Hepatitis C (complications, drug therapy, genetics)
• Humans
• Interferon-alpha (adverse effects, therapeutic use)
• Liver Cirrhosis (drug therapy, etiology)
• Male
• Middle Aged
• Polyethylene Glycols (adverse effects, therapeutic use)
• Proline (adverse effects, analogs & derivatives, therapeutic use)
• Prospective Studies
• Protease Inhibitors (adverse effects, therapeutic use)
• Recombinant Proteins (adverse effects, therapeutic use)
• Ribavirin (adverse effects, therapeutic use)
• Spain