Infections during peginterferon/ribavirin therapy are associated with the magnitude of decline in absolute lymphocyte count: Results of the IDEAL study

Michael T. Melia, Norbert Bräu, Fred Poordad, Eric J. Lawitz, Mitchell L. Shiffman, John G. McHutchison, Andrew J. Muir, Greg W. Galler, Lisa M. Nyberg, William M. Lee, Eugene Schiff, Jianmin Long, Stephanie Noviello, Clifford A. Brass, Lisa D. Pedicone, Mark S. Sulkowski

Research output: Contribution to journalArticle

8 Citations (Scopus)

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. Ontreatment leukocyte counts were obtained every 2-6 weeks. Dose reduction was required for a neutrophil count <0.75 × 109 cells/L, and treatment discontinuation was required for a neutrophil count <0.5 × 109 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 × 109 cells/L, but only 242 (8%) sustained an infection and had a neutrophil count <0.75 × 109 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 × 109 cells/L).

Original languageEnglish (US)
Pages (from-to)960-969
Number of pages10
JournalClinical Infectious Diseases
Volume58
Issue number7
DOIs
StatePublished - 2014

Fingerprint

Ribavirin
Lymphocyte Count
Neutrophils
Infection
Interferons
Therapeutics
Logistic Models
Lymphopenia
Granulocyte Colony-Stimulating Factor
Chronic Hepatitis C
Neutropenia
Leukocyte Count
Hepacivirus
Leukocytes
Genotype
Research Personnel
Incidence

Keywords

  • Hepatitis C virus
  • Infections
  • Interferon
  • Lymphopenia
  • Neutropenia

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Infections during peginterferon/ribavirin therapy are associated with the magnitude of decline in absolute lymphocyte count : Results of the IDEAL study. / Melia, Michael T.; Bräu, Norbert; Poordad, Fred; Lawitz, Eric J.; Shiffman, Mitchell L.; McHutchison, John G.; Muir, Andrew J.; Galler, Greg W.; Nyberg, Lisa M.; Lee, William M.; Schiff, Eugene; Long, Jianmin; Noviello, Stephanie; Brass, Clifford A.; Pedicone, Lisa D.; Sulkowski, Mark S.

In: Clinical Infectious Diseases, Vol. 58, No. 7, 2014, p. 960-969.

Research output: Contribution to journalArticle

Melia, MT, Bräu, N, Poordad, F, Lawitz, EJ, Shiffman, ML, McHutchison, JG, Muir, AJ, Galler, GW, Nyberg, LM, Lee, WM, Schiff, E, Long, J, Noviello, S, Brass, CA, Pedicone, LD & Sulkowski, MS 2014, 'Infections during peginterferon/ribavirin therapy are associated with the magnitude of decline in absolute lymphocyte count: Results of the IDEAL study', Clinical Infectious Diseases, vol. 58, no. 7, pp. 960-969. https://doi.org/10.1093/cid/ciu009
Melia, Michael T. ; Bräu, Norbert ; Poordad, Fred ; Lawitz, Eric J. ; Shiffman, Mitchell L. ; McHutchison, John G. ; Muir, Andrew J. ; Galler, Greg W. ; Nyberg, Lisa M. ; Lee, William M. ; Schiff, Eugene ; Long, Jianmin ; Noviello, Stephanie ; Brass, Clifford A. ; Pedicone, Lisa D. ; Sulkowski, Mark S. / Infections during peginterferon/ribavirin therapy are associated with the magnitude of decline in absolute lymphocyte count : Results of the IDEAL study. In: Clinical Infectious Diseases. 2014 ; Vol. 58, No. 7. pp. 960-969.
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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. Ontreatment leukocyte counts were obtained every 2-6 weeks. Dose reduction was required for a neutrophil count <0.75 × 109 cells/L, and treatment discontinuation was required for a neutrophil count <0.5 × 109 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 × 109 cells/L, but only 242 (8{\%}) sustained an infection and had a neutrophil count <0.75 × 109 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 × 109 cells/L).",
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T1 - Infections during peginterferon/ribavirin therapy are associated with the magnitude of decline in absolute lymphocyte count

T2 - Results of the IDEAL study

AU - Melia, Michael T.

AU - Bräu, Norbert

AU - Poordad, Fred

AU - Lawitz, Eric J.

AU - Shiffman, Mitchell L.

AU - McHutchison, John G.

AU - Muir, Andrew J.

AU - Galler, Greg W.

AU - Nyberg, Lisa M.

AU - Lee, William M.

AU - Schiff, Eugene

AU - Long, Jianmin

AU - Noviello, Stephanie

AU - Brass, Clifford A.

AU - Pedicone, Lisa D.

AU - Sulkowski, Mark S.

PY - 2014

Y1 - 2014

N2 - 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. Ontreatment leukocyte counts were obtained every 2-6 weeks. Dose reduction was required for a neutrophil count <0.75 × 109 cells/L, and treatment discontinuation was required for a neutrophil count <0.5 × 109 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 × 109 cells/L, but only 242 (8%) sustained an infection and had a neutrophil count <0.75 × 109 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 × 109 cells/L).

AB - 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. Ontreatment leukocyte counts were obtained every 2-6 weeks. Dose reduction was required for a neutrophil count <0.75 × 109 cells/L, and treatment discontinuation was required for a neutrophil count <0.5 × 109 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 × 109 cells/L, but only 242 (8%) sustained an infection and had a neutrophil count <0.75 × 109 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 × 109 cells/L).

KW - Hepatitis C virus

KW - Infections

KW - Interferon

KW - Lymphopenia

KW - Neutropenia

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DO - 10.1093/cid/ciu009

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