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 language | English (US) |
|---|---|
| Pages (from-to) | 960-969 |
| Number of pages | 10 |
| Journal | Clinical Infectious Diseases |
| Volume | 58 |
| Issue number | 7 |
| DOIs | |
| State | Published - 2014 |
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Keywords
- Hepatitis C virus
- Infections
- Interferon
- Lymphopenia
- Neutropenia
ASJC Scopus subject areas
- Medicine(all)
- 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; 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.
In: Clinical Infectious Diseases, Vol. 58, No. 7, 2014, p. 960-969.Research output: Contribution to journal › Article
}
TY - JOUR
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
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
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
UR - http://www.scopus.com/inward/record.url?scp=84918788756&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84918788756&partnerID=8YFLogxK
U2 - 10.1093/cid/ciu009
DO - 10.1093/cid/ciu009
M3 - Article
C2 - 24399086
AN - SCOPUS:84918788756
VL - 58
SP - 960
EP - 969
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
SN - 1058-4838
IS - 7
ER -