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

Hepatology. 2013 Mar;57(3):974-84. doi: 10.1002/hep.26096. Epub 2013 Feb 11.

Abstract

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.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • 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