title: A Low Neutrophil CD64 Index Is Associated with Sustained Remission During Infliximab Maintenance Therapy.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  Neutrophil CD64 index >1 is a significant risk factor for treatment failure during infliximab maintenance therapy.
authors.affiliation: *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.
authors.forename: Phillip
authors.initials: P
authors.lastname: Minar
authors.forename: Kimberly
authors.initials: K
authors.lastname: Jackson
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Tsai
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rosen
authors.forename: Michael
authors.initials: M
authors.lastname: Northcutt
authors.forename: Marat
authors.initials: M
authors.lastname: Khodoun
authors.forename: Fred D
authors.initials: FD
authors.lastname: Finkelman
authors.forename: Lee A
authors.initials: LA
authors.lastname: Denson
mesh_terms: D000293:Adolescent; D002648:Child; D003424:Crohn Disease / Q000097:blood* / Q000188:drug therapy; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D000069285:Infliximab / Q000627:therapeutic use*; D007958:Leukocyte Count; D060046:Maintenance Chemotherapy; D008297:Male; D009504:Neutrophils; D017452:Receptors, IgG / Q000097:blood*; D012044:Regression Analysis; D012307:Risk Factors; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D005765:Gastrointestinal Agents; D017452:Receptors, IgG; D000069285:Infliximab