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A Low Neutrophil CD64 Index Is Associated with Sustained Remission During Infliximab Maintenance Therapy
Phillip Minar1, Kimberly Jackson, Yi-Ting Tsai
1*Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; †Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio; and ‡Division of Cellular and Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Insights
Elevated neutrophil CD64 index in asymptomatic children with Crohn's disease (CD) predicts infliximab treatment failure. This biomarker can help identify patients at risk for worsening disease during maintenance therapy.
Area of Science:
- Gastroenterology
- Immunology
- Pediatric Medicine
Background:
- Previous research indicated elevated CD64 on neutrophils in newly diagnosed pediatric Crohn's disease (CD).
- CD64 expression on neutrophils may serve as an indicator of disease activity or treatment response.
Purpose of the Study:
- To determine if elevated neutrophil CD64 expression in asymptomatic pediatric CD patients predicts infliximab maintenance treatment failure.
- To assess the utility of CD64 as a predictive biomarker for treatment outcomes in pediatric CD.
Main Methods:
- 36 pediatric CD patients in remission on maintenance infliximab were enrolled.
- Neutrophil CD64 index and infliximab trough concentrations were measured.
- Treatment failure was defined by clinical, endoscopic, or surgical criteria over one year.
Main Results:
- 15 out of 36 subjects experienced treatment failure within one year.
- Asymptomatic patients with a neutrophil CD64 index >1 had a significantly higher probability of treatment failure (log-rank = 0.002).
- Neutrophil CD64 index >1 and nonwhite race were identified as risk factors for treatment failure; infliximab trough levels did not differ between groups.
Conclusions:
- Elevated neutrophil CD64 index (>1) is a significant risk factor for infliximab treatment failure in pediatric Crohn's disease patients.
- CD64 serves as a valuable predictive biomarker for identifying children with CD at risk of losing response to infliximab maintenance therapy.
Background:
We have previously shown that CD64 surface expression on circulating neutrophils is significantly elevated in children with newly diagnosed Crohn's disease (CD). Our primary aim was to investigate whether elevations in neutrophil CD64 in asymptomatic patients could be used to predict treatment failure during maintenance infliximab.
Methods:
Pediatric CD subjects receiving maintenance infliximab in clinical remission (short pediatric CD activity index [shPCDAI] <15) were enrolled. We measured neutrophil CD64 expression (CD64 index, Trillium Diagnostics, LLC) and infliximab trough concentrations. Infliximab failure was defined as an shPCDAI >15 on 2 consecutive infusions, discontinuation of infliximab, hospitalization, endoscopic ulcerations, or surgery during the following year of maintenance infliximab.
Results:
We enrolled 36 subjects, 22/36 were male and 29/36 were white. Mean (SD) age at study entry was 15 (4) years with a median of 14 (5-20) infusions before study entry. 4/36 were receiving a concurrent immunomodulator. Over 1 year, 15/36 subjects were classified as infliximab failures. Asymptomatic subjects with a neutrophil CD64 index >1 at study entry had a higher probability of treatment failure compared with asymptomatic subjects with a CD64 index <1 (log-rank = 0.002). We found only neutrophil CD64 index >1 and nonwhite race were risk factors for treatment failure by univariate regression analysis. We found no difference in the mean infliximab trough concentration at study entry between treatment failures (2.8 μg/mL, SD, 1.2) and subjects remaining in remission on infliximab (4.2 μg/mL, SD, 3.4; P = 0.17).
Conclusions:
Neutrophil CD64 index >1 is a significant risk factor for treatment failure during infliximab maintenance therapy.
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