title: Antibodies to infliximab are associated with lower infliximab levels and increased likelihood of surgery in pediatric IBD.
abstract: BACKGROUND
  Adult studies suggest antibodies to infliximab (ATI) correlate with loss of response in inflammatory bowel disease but pediatric data are limited.
  
  
  METHODS
  We conducted a cross-sectional study of trough infliximab levels and ATI in 134 pediatric and young adult patients receiving infliximab. At the time serum was obtained demographics, disease phenotype, duration of infliximab therapy, use of combination therapy (methotrexate or 6-mercaptopurine with infliximab), and surgery were recorded.
  
  
  RESULTS
  Assays were performed on 134 subjects currently receiving infliximab (85 male; mean age, 17.3 ± 4.3 years; 114 Crohn's disease and 20 ulcerative colitis). Infliximab use ranged from 12 days to 12 years: median 2.0 (interquartile range [1.1-4.3]) years. Twenty-seven of 134 (20%) patients had ATI ≥5 U/mL. Of patients with ATI ≥5 U/mL, 59% had infliximab levels <5 μg/mL, compared with 14% of patients with ATI <5 U/mL (P < 0.001). Ten (7%) patients (9 Crohn's disease, 1 ulcerative colitis) underwent bowel resections after beginning infliximab infusions. Sixty percent who underwent surgery had ATI ≥12 U/mL; in contrast, only 8% of patients who did not undergo surgery had ATI ≥12 U/mL (P = 0.01). At the time of serum sampling, 50 (37%) patients were receiving combination therapy, compared with 84 (63%) on infliximab alone. Combination therapy at the time of serum sampling did not correlate with either increase infliximab levels or lower ATI compared with infliximab monotherapy. However, prior immunomodulator use was associated with lower antibody levels (P = 0.007).
  
  
  CONCLUSIONS
  ATI correlates with reduction in infliximab level and a higher risk of surgery in patients with inflammatory bowel disease.
authors.affiliation: *Pediatric Inflammatory Bowel Disease Center, Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Boston Children's Hospital, Boston, Massachusetts; †Boston Children's Hospital Clinical Research Center, Boston, Massachusetts; and ‡Prometheus Laboratories Inc., San Diego, California.
authors.forename: Naamah L
authors.initials: NL
authors.lastname: Zitomersky
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Atkinson
authors.forename: Kerri
authors.initials: K
authors.lastname: Fournier
authors.forename: Paul D
authors.initials: PD
authors.lastname: Mitchell
authors.forename: Julia Bender
authors.initials: JB
authors.lastname: Stern
authors.forename: Michael C
authors.initials: MC
authors.lastname: Butler
authors.forename: Lori
authors.initials: L
authors.lastname: Ashworth
authors.forename: Scott
authors.initials: S
authors.lastname: Hauenstein
authors.forename: Linda
authors.initials: L
authors.lastname: Heiner
authors.forename: Emil
authors.initials: E
authors.lastname: Chuang
authors.forename: Sharat
authors.initials: S
authors.lastname: Singh
authors.forename: Athos
authors.initials: A
authors.lastname: Bousvaros
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000097:blood* / Q000627:therapeutic use; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003093:Colitis, Ulcerative / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D000069285:Infliximab; D008297:Male; D011379:Prognosis; D055815:Young Adult
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D000069285:Infliximab