title: Serum Infliximab, Antidrug Antibodies, and Tumor Necrosis Factor Predict Sustained Response in Pediatric Crohn's Disease.
abstract: Serum infliximab (s-IFX) levels, antibodies to IFX (ATI), and inflammatory markers are important in predicting clinical outcomes in adults, but their roles in pediatric Crohn's disease (CD) require further study. The primary aim of this study was to determine the association between serologic parameters during induction and ongoing IFX therapy at 12 months in pediatric CD.
  
  
  
  S-IFX, ATI, serum tumor necrosis factor alpha (s-TNF-α), and C-reactive protein were measured at IFX initiation, 10 weeks, 6 months, and 12 months in a prospective cohort study of children with CD at a single tertiary care center.
  
  
  
  At 12 months, 60 of 77 participants (78%) remained on IFX. Participants who completed 12 months of IFX had higher 10-week median s-IFX levels (20.40 μg/mL; interquartile range [IQR], 11.20-35.00] versus 8.70 μg/mL; IQR 0.90-16.90; P = 0.01), a greater proportion with undetectable 10-week ATI (P = 0.008), and a greater median change in s-TNF-α between baseline and week 10 (-5.96 pg/mL; IQR, -8.73 to -4.17 versus -1.76 pg/mL; IQR, -5.60 to 0.30; P = 0.006). Receiver operating characteristic analysis to predict ongoing IFX at 12 months showed area under the curve (95% confidence interval) for 10-week s-IFX and change in s-TNF-α from baseline to 10 weeks to be 0.71 (0.54-0.88) and 0.74 (0.58-0.91), respectively. C-reactive protein was not associated with ongoing therapy.
  
  
  
  ATI, s-IFX, and s-TNF-α during IFX induction are associated with 12-month clinical outcomes in pediatric CD. Future studies are needed to further define the clinical role of s-TNF-α measurement and to compare the clinical utility of 10 and 14-week ATI and s-IFX levels.
authors.affiliation: *Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; †Department of Gastroenterology, Seattle Children's Hospital, Seattle, Washington; ‡Departments of Pediatrics and Medicine, Division of Nephrology, Stanford University School of Medicine, Stanford, California; §Janssen Pharmaceuticals, Horsham, Pennsylvania; ‖Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; ¶Nestlé Health Science, Vevey, Switzerland; #Department of Pediatrics, Division of Nephrology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; and **Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Ronen
authors.initials: R
authors.lastname: Stein
authors.forename: Dale
authors.initials: D
authors.lastname: Lee
authors.forename: Mary B
authors.initials: MB
authors.lastname: Leonard
authors.forename: Meena
authors.initials: M
authors.lastname: Thayu
authors.forename: Lee A
authors.initials: LA
authors.lastname: Denson
authors.forename: Emil
authors.initials: E
authors.lastname: Chuang
authors.forename: Rita
authors.initials: R
authors.lastname: Herskovitz
authors.forename: Theresa
authors.initials: T
authors.lastname: Kerbowski
authors.forename: Robert N
authors.initials: RN
authors.lastname: Baldassano
mesh_terms: D000293:Adolescent; D000906:Antibodies / Q000097:blood*; D019540:Area Under Curve; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000097:blood* / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005765:Gastrointestinal Agents / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000069285:Infliximab / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D060046:Maintenance Chemotherapy; D008297:Male; D011446:Prospective Studies; D012372:ROC Curve; D012074:Remission Induction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000097:blood*; D055815:Young Adult
chemical_list: D000906:Antibodies; D005765:Gastrointestinal Agents; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D000069285:Infliximab