Anemia during treatment with peginterferon Alfa-2b/ribavirin and boceprevir: Analysis from the serine protease inhibitor therapy 2 (SPRINT-2) trial.

Abstract

UNLABELLED:

Boceprevir (BOC) added to peginterferon alfa-2b (PegIFN) and ribavirin (RBV) significantly increases sustained virologic response (SVR) rates over PegIFN/RBV alone in previously untreated adults with chronic hepatitis C genotype 1. We evaluate the relationship of incident anemia with triple therapy. A total of 1,097 patients received a 4-week lead-in of PegIFN/RBV followed by: (1) placebo plus PegIFN/RBV for 44 weeks (PR48); (2) BOC plus PegIFN/RBV using response-guided therapy (BOC/RGT); and (3) BOC plus PegIFN/RBV for 44 weeks (BOC/PR48). The management of anemia (hemoglobin [Hb]<10 g/dL) included RBV dose reduction and/or erythropoietin (EPO) use. A total of 1,080 patients had ≥1 Hb measurement during treatment. The incidence of anemia was 50% in the BOC arms combined (363/726) and 31% in the PR48 arm (108/354, P<0.001). Among BOC recipients, lower baseline Hb and creatinine clearance were associated with incident anemia. In the BOC-containing arms, anemia was managed by the site investigators as follows: EPO without RBV dose reduction, 38%; RBV dose reduction without EPO, 8%; EPO with RBV dose reduction, 40%; and neither RBV dose reduction nor EPO, 14%. SVR rates were not significantly affected by management strategy (70%-74%), and overall patients with anemia had higher rates of SVR than those who did not develop anemia (58%). Serious and life-threatening adverse events (AEs) and discontinuations due to AEs among BOC-treated patients did not differ by EPO use.

CONCLUSION:

With BOC/PR therapy, SVR rates in patients with incident anemia were higher than nonanemic patients and did not vary significantly according to the investigator-selected approach for anemia management. Prospective studies are needed to confirm this observation.

• Authors: Mark S Sulkowski, Fred Poordad, Michael P Manns, Jean-Pierre Bronowicki, K Rajender Reddy, Stephen A Harrison, Nezam H Afdhal, Heather L Sings, Lisa D Pedicone, Kenneth J Koury, Vilma Sniukiene, Margaret H Burroughs, Janice K Albrecht, Clifford A Brass, Ira M Jacobson, SPRINT-2 Trial Investigators
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 57 Issue 3 Pg. 974-84 (Mar 2013) ISSN: 1527-3350 [Electronic] United States
• PMID: 23081753 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 American Association for the Study of Liver Diseases.

Chemical References

• Antiviral Agents
• Hematinics
• Hemoglobins
• Interferon alpha-2
• Interferon-alpha
• Placebos
• Recombinant Proteins
• Serine Proteinase Inhibitors
• Erythropoietin
• 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

• Adult
• Anemia (chemically induced, drug therapy)
• Antiviral Agents (administration & dosage, adverse effects)
• Drug Therapy, Combination (adverse effects)
• Erythropoietin (administration & dosage, adverse effects)
• Female
• Hematinics (administration & dosage, adverse effects)
• Hemoglobins (metabolism)
• Hepatitis C, Chronic (drug therapy)
• Humans
• Interferon alpha-2
• Interferon-alpha (administration & dosage, adverse effects)
• Male
• Placebos
• Polyethylene Glycols (administration & dosage, adverse effects)
• Proline (administration & dosage, adverse effects, analogs & derivatives)
• Recombinant Proteins (administration & dosage, adverse effects)
• Ribavirin (administration & dosage, adverse effects)
• Serine Proteinase Inhibitors (administration & dosage, adverse effects)
• Treatment Outcome