title: The association of infliximab trough levels with disease activity in pediatric inflammatory bowel disease.
abstract: OBJECTIVE
  Low serum trough levels (TLs) of infliximab (IFX) and antibodies to IFX (ATIs) are associated with the loss of therapeutic response in adults with inflammatory bowel disease (IBD) receiving IFX. Until now, pediatric data are scarce. Therefore, we aimed to cross-sectionally investigate the association between ATIs and IFX TLs, and clinical and biochemical disease activity in children receiving IFX for IBD.
  
  
  METHODS
  Children aged <18 years receiving IFX maintenance treatment for Crohn's disease (CD) or ulcerative colitis (UC) at three Dutch hospitals were included. Prior to two consecutive IFX infusions, IFX TLs and ATI levels were measured. Clinical disease activity was determined by Pediatric Crohn's Disease Activity Index (PCDAI) and Pediatric Ulcerative Colitis Activity Index (PUCAI), for CD and UC, respectively. Biochemical disease activity was assessed by serum C-reactive protein (CRP) and fecal calprotectin (FC). Clinical remission was defined as a PUCAI or PCDAI score of <10. Therapeutic range of IFX was considered 3-7 µg/ml.
  
  
  RESULTS
  Thirty-nine patients were included (31 CD; 16 females). Median age was 15 years. Median IFX TL was 3.5 µg/ml [IQR 2-7]. Subtherapeutic and supratherapeutic TLs were found in 38% and 23% of children, respectively. ATIs were detected in four patients. A correlation was found between IFX TL and CRP [rs = -0.51; p < 0.01] and FC [rs = -0.49; p < 0.01]. However, when only clinical disease activity was considered, no difference in median TL was found between remission and active disease (resp. 3.5 µg/ml [IQR 2-5] and 2.3 µg/ml [IQR 0.3-4.6]; p = 0.2).
  
  
  CONCLUSIONS
  IFX TLs are related to biochemical markers of disease activity. This could provide a rationale for monitoring TLs in children receiving IFX for IBD.
authors: Department of Pediatric Gastroenterology and Nutrition, Academic Medical Center , Amsterdam , The Netherlands.
authors: Daniël R
authors: DR
authors: Hoekman
authors: Johannan F
authors: JF
authors: Brandse
authors: Tim G
authors: TG
authors: de Meij
authors: Thalia Z
authors: TZ
authors: Hummel
authors: Mark
authors: M
authors: Löwenberg
authors: Marc A
authors: MA
authors: Benninga
authors: Geert R
authors: GR
authors: D'Haens
authors: Angelika
authors: A
authors: Kindermann
mesh_terms: D000293:Adolescent; D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis*; D002648:Child; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D003424:Crohn Disease / Q000188:drug therapy*; D003430:Cross-Sectional Studies; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage*; D006801:Humans; D000069285:Infliximab / Q000008:administration & dosage*; D039841:Leukocyte L1 Antigen Complex / Q000032:analysis*; D008297:Male; D012074:Remission Induction
chemical_list: D015415:Biomarkers; D005765:Gastrointestinal Agents; D039841:Leukocyte L1 Antigen Complex; D002097:C-Reactive Protein; D000069285:Infliximab
keywords: Children; Crohn’s disease; inflammatory bowel disease; infliximab trough levels; ulcerative colitis