title: Infections during peginterferon/ribavirin therapy are associated with the magnitude of decline in absolute lymphocyte count: results of the IDEAL study.
abstract: BACKGROUND
  Myelosuppression due to pegylated interferon (peg-IFN) is common during treatment for hepatitis C virus. The relationship between infection risk and decreases in leukocyte lines, however, is not well established. The objective of this analysis was to determine the incidence of and risk factors for infections during peg-IFN/ribavirin (RBV) therapy.
  
  
  METHODS
  A total of 3070 treatment-naive, chronic hepatitis C genotype 1-infected patients were treated for up to 48 weeks with peg-IFN alfa-2b 1.5 µg/kg/week or 1 µg/kg/week, or peg-IFN alfa-2a 180 µg/week plus RBV. On-treatment leukocyte counts were obtained every 2-6 weeks. Dose reduction was required for a neutrophil count <0.75 × 10(9) cells/L, and treatment discontinuation was required for a neutrophil count <0.5 × 10(9) cells/L. Granulocyte colony-stimulating factor was prohibited. Data on infections were captured at each study visit and categorized according to MedDRA version 13.0.
  
  
  RESULTS
  A total of 581 (19%) patients experienced moderate, severe, or life-threatening infections as assessed by the investigator; 648 (21%) patients had at least 1 neutrophil count <0.75 × 10(9) cells/L, but only 242 (8%) sustained an infection and had a neutrophil count <0.75 × 10(9) cells/L at any time while on treatment. Twelve patients had severe or life-threatening infection and grade 3/4 neutropenia, but only 4 had temporally related infections. In a multivariate logistic regression model, nadir lymphocyte count, history of depression, and female sex, but not nadir neutrophil count, were associated with moderate, severe, or life-threatening infection.
  
  
  CONCLUSIONS
  Nadir lymphocyte count, not nadir neutrophil count, was independently associated with moderate, severe, or life-threatening infections in the IDEAL study. Clinicians should be aware of their patients' absolute lymphocyte counts during peg-IFN/RBV therapy; peg-IFN dose reductions may be a consideration in patients with significant lymphocytopenia (<0.5 × 10(9) cells/L).
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Melia
authors.forename: Norbert
authors.initials: N
authors.lastname: Bräu
authors.forename: Fred
authors.initials: F
authors.lastname: Poordad
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Lawitz
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Shiffman
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Muir
authors.forename: Greg W
authors.initials: GW
authors.lastname: Galler
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Nyberg
authors.forename: William M
authors.initials: WM
authors.lastname: Lee
authors.forename: Eugene
authors.initials: E
authors.lastname: Schiff
authors.forename: Jianmin
authors.initials: J
authors.lastname: Long
authors.forename: Stephanie
authors.initials: S
authors.lastname: Noviello
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Brass
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Pedicone
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sulkowski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D007239:Infections / Q000150:complications / Q000453:epidemiology*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects* / Q000627:therapeutic use; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009504:Neutrophils / Q000187:drug effects; D011092:Polyethylene Glycols / Q000009:adverse effects* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012254:Ribavirin / Q000009:adverse effects* / Q000627:therapeutic use; D018570:Risk Assessment; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b
keywords: hepatitis C virus; infections; interferon; lymphopenia; neutropenia