title: Infliximab Optimization Based on Therapeutic Drug Monitoring in Pediatric Inflammatory Bowel Disease.
abstract: Infliximab (IFX) is an effective treatment for the management of moderate to severe inflammatory bowel disease (IBD). Low-serum IFX levels are associated with the development of antibodies to IFX (ATI), which subsequently associated with clinical relapse and increased morbidity. The primary purpose of this study is to examine the relation between dose and interval to IFX level. Secondary goal is to evaluate the relation between IFX level and ATI in a pediatric IBD population.
  
  
  
  We performed a retrospective chart review of all children diagnosed with IBD and treated with IFX at a tertiary care pediatric IBD center. We performed our analysis based on prescribed dosing intervals and rounded dose up to 5 or 10 mg/kg as indicated in clinical practice.
  
  
  
  Our study included 278 samples from 129 children on IFX. ATI were detected in 37 samples (13.3%). Low IFX levels (<3 μg/mL) were detected in 37.2% of children receiving IFX. Samples with ATI present had significantly lower levels of IFX than samples in which ATI were not present. For the dose 5 mg/kg, Q6 dosing had significantly higher IFX levels than Q8 dosing (P = 0.009). Higher IFX levels were seen with interval shortening rather than dose escalation.
  
  
  
  We demonstrate that low IFX levels are associated with development of immunogenicity to IFX as measured by ATI. We demonstrate that interval shortening rather than dose escalation results in higher IFX levels. We suggest that given the high number of IFX levels below 3 μg/mL in patients, early IFX level evaluation or primary initiation of Q6 week dosing be considered.
authors.affiliation: *Department of Pediatrics, Emory University School of Medicine †Children's Healthcare of Atlanta ‡Georgia Regents University, August.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Hofmekler
authors.forename: Madeline
authors.initials: M
authors.lastname: Bertha
authors.forename: Courtney
authors.initials: C
authors.lastname: McCracken
authors.forename: Benadette
authors.initials: B
authors.lastname: Martineau
authors.forename: Elizabeth
authors.initials: E
authors.lastname: McKinnon
authors.forename: Bess T
authors.initials: BT
authors.lastname: Schoen
authors.forename: Barbara O
authors.initials: BO
authors.lastname: McElhanon
authors.forename: Gayathri
authors.initials: G
authors.lastname: Tenjarla
authors.forename: Subra
authors.initials: S
authors.lastname: Kugathasan
authors.forename: Cary G
authors.initials: CG
authors.lastname: Sauer
mesh_terms: D000293:Adolescent; D000906:Antibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; 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; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D004361:Drug Tolerance / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D005765:Gastrointestinal Agents / Q000097:blood / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D000069285:Infliximab / Q000097:blood / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D015415:Biomarkers; D005765:Gastrointestinal Agents; D000069285:Infliximab