title: Early infliximab trough levels are associated with persistent remission in pediatric patients with inflammatory bowel disease.
abstract: BACKGROUND
  Low infliximab (IFX) trough levels and high anti-infliximab antibodies (ATI) levels are associated with loss of response to IFX. Optimizing IFX levels to maintain target concentrations before loss of response may improve long-term efficacy. We hypothesized that trough levels at week 14 are predictive of IFX durability.
  
  
  METHODS
  A prospective observational cohort of pediatric patients with inflammatory bowel disease initiating IFX had IFX and ATI levels drawn at weeks 14 and 54. Primary outcome was week 54 persistent remission (PR), defined as clinical remission without IFX dose intensification. Univariate analyses tested associations of week 14 IFX (IFX14) and ATI (ATI14) levels, clinical and laboratory data with week 54 outcomes. Receiver operating curve analysis and positive and negative predictive values for IFX14 cut-off points were examined.
  
  
  RESULTS
  Of 58 patients enrolled, 8 (13%) stopped IFX before week 14 and 4 discontinued IFX between weeks 14 and 54. IFX14 level (P = 0.03), baseline C-reactive protein (CRP) level (P = 0.01), and week 14 CRP (CRP14) level (P = 0.0001) were associated with PR. A model with IFX14 levels predicting PR had an area under the receiver operating curve of 0.68 and a model with both IFX14 level and CRP14 >1.0 mg/dL had an area under the receiver operating curve of 0.74. IFX14 cut points of >3, >4, and >7 µg/mL had positive predictive values of 64%, 76% and 100%, respectively, for predicting PR.
  
  
  CONCLUSIONS
  Both IFX levels and CRP at week 14 were significantly associated with week 54 efficacy. A model combining both CRP and IFX at week 14 may help predict remission at week 54.
authors.affiliation: Departments of *Pediatrics and †Medicine, Cedars-Sinai Medical Center, Los Angeles, California; ‡F. Widjaja Foundation Inflammatory Bowel and Immunobiology Institute, Cedars-Sinai Medical Center, Los Angeles, California; and §Department of Biostatistics, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Namita
authors.initials: N
authors.lastname: Singh
authors.forename: Casey J
authors.initials: CJ
authors.lastname: Rosenthal
authors.forename: Gil Y
authors.initials: GY
authors.lastname: Melmed
authors.forename: James
authors.initials: J
authors.lastname: Mirocha
authors.forename: Sharmayne
authors.initials: S
authors.lastname: Farrior
authors.forename: Silvia
authors.initials: S
authors.lastname: Callejas
authors.forename: Bhavna
authors.initials: B
authors.lastname: Tripuraneni
authors.forename: Shervin
authors.initials: S
authors.lastname: Rabizadeh
authors.forename: Marla C
authors.initials: MC
authors.lastname: Dubinsky
mesh_terms: D000293:Adolescent; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D000911:Antibodies, Monoclonal / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D003093:Colitis, Ulcerative / Q000097:blood / Q000188:drug therapy*; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D005765:Gastrointestinal Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D000069285:Infliximab; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction; D014018:Tissue Distribution
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D002097:C-Reactive Protein; D000069285:Infliximab