title: Adalimumab therapy in children with Crohn disease previously treated with infliximab.
abstract: OBJECTIVE
  Adalimumab, a humanised anti-tumour necrosis factor antibody, is an effective treatment in adult patients with refractory Crohn disease (CD). The available literature on its efficacy in children remains limited. We aimed to evaluate the real-world efficacy in paediatric patients with CD and compare the efficacy between infliximab (IFX) nonresponders and patients who lost response to IFX.
  
  
  METHODS
  All Dutch patients with CD receiving adalimumab before the age of 18 years after previous IFX therapy were identified. We analysed longitudinal disease activity, assessed by the mathematically weighted Pediatric Crohn's Disease Activity Index (wPCDAI) or the physician global assessment (PGA), and adverse events (AEs).
  
  
  RESULTS
  Fifty-three patients with CD were included. Twelve patients received monotherapy and the others received combination treatment with thiopurines (n = 21), methotrexate (n = 11), steroids (n = 7), or exclusive enteral nutrition (n = 2). Median follow-up was 12 months (interquartile range 5-23). Remission was reached in 34 patients (64%, wPCDAI < 12.5 or PGA = 0) after a median of 3.3 months, and maintained by 50% for 2 years. Eleven patients (21%) reached response but not remission (decrease in wPCDAI ≥ 17.5 or decrease in PGA). Eighteen patients (34%) failed adalimumab treatment because of nonresponse (n = 4), lost response (n = 11), or AEs (n = 3). More IFX nonresponders failed adalimumab treatment than patients who lost response to IFX (2/3 vs 8/34, hazard ratio 18.8, 95% confidence interval 1.1-303.6). Only 1 patient encountered a serious AE, a severe but nonfatal infection.
  
  
  CONCLUSIONS
  In clinical practice, adalimumab induces remission in two-thirds of children with IFX refractory CD.
authors.affiliation: *Pediatric Gastroenterology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam †Pediatric Gastroenterology, Radboud University Nijmegen Medical Centre, Nijmegen ‡Pediatric Gastroenterology, Wilhelmina Children's Hospital-University Medical Center, Utrecht §Pediatric Gastroenterology, Emma Children's Hospital-Academic Medical Center, Amsterdam ||Pediatric Gastroenterology, Beatrix Children's Hospital-University Medical Center Groningen, Groningen ¶Pediatric Gastroenterology, VU University Medical Center, Amsterdam #Pediatric Gastroenterology, Willem-Alexander Kinderziekenhuis-Leiden University Medical Center, Leiden **Pediatric Gastroenterology, Isala Hospital, Zwolle ††Pediatric Gastroenterology, Catharina Hospital, Eindhoven ‡‡Pediatric Gastroenterology, Maastricht University Medical Center, Maastricht §§Pediatric Gastroenterology, Amphia Hospital, Breda ||||Pediatric Gastroenterology, Medisch Spectrum Twente, Enschede ¶¶Pediatric Gastroenterology, Gelre Hospitals, Apeldoorn, The Netherlands.
authors.forename: Martinus
authors.initials: M
authors.lastname: Cozijnsen
authors.forename: Vera
authors.initials: V
authors.lastname: Duif
authors.forename: Freddy
authors.initials: F
authors.lastname: Kokke
authors.forename: Angelika
authors.initials: A
authors.lastname: Kindermann
authors.forename: Patrick
authors.initials: P
authors.lastname: van Rheenen
authors.forename: Tim
authors.initials: T
authors.lastname: de Meij
authors.forename: Maaike
authors.initials: M
authors.lastname: Schaart
authors.forename: Gerard
authors.initials: G
authors.lastname: Damen
authors.forename: Obbe
authors.initials: O
authors.lastname: Norbruis
authors.forename: Rolf
authors.initials: R
authors.lastname: Pelleboer
authors.forename: Anita
authors.initials: A
authors.lastname: Van den Neucker
authors.forename: Herbert
authors.initials: H
authors.lastname: van Wering
authors.forename: Thalia
authors.initials: T
authors.lastname: Hummel
authors.forename: Johanna
authors.initials: J
authors.lastname: Oudshoorn
authors.forename: Johanna
authors.initials: J
authors.lastname: Escher
authors.forename: Lissy
authors.initials: L
authors.lastname: de Ridder
mesh_terms: D000068879:Adalimumab; D000293:Adolescent; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D003424:Crohn Disease / Q000188:drug therapy*; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D019233:Retreatment; D012189:Retrospective Studies; D012720:Severity of Illness Index; D017211:Treatment Failure
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069285:Infliximab; D000068879:Adalimumab