title: Infliximab maintains durable response and facilitates catch-up growth in luminal pediatric Crohn's disease.
abstract: BACKGROUND
  Infliximab induces and maintains clinical remission in children with Crohn's disease (CD), but specifically pediatric long-term data remain sparse.
  
  
  METHODS
  Patients (N = 195) who received infliximab ± immunomodulator for luminal CD were retrospectively reviewed. Outcomes included clinical response, linear growth, and mucosal healing. Durability of response was assessed using Cox proportional hazards models. Levels of infliximab and antibodies (antibodies to infliximab) were measured when response was lost.
  
  
  RESULTS
  Among 195 patients (median age, 13.9 yr; median CD duration, 1.6 yr), 81% experienced complete response (judged by physician global assessment and pediatric Crohn's disease activity index ≤10). Longer duration of diagnosed CD and female gender were associated with lower response. During first year of follow-up, 35% of subjects had regimen individualized through dose escalation/interval shortening. Despite regimen optimization, 16/157 complete responders experienced loss of response at a rate of 2% to 6% per year over 5 years, associated with development of antibodies to infliximab. Concurrent immunomodulation for ≥30 weeks significantly decreased loss of response (hazard ratio = 0.25, 95% confidence interval, 0.08-0.76; P = 0.014). Follow-up endoscopic examination was performed in 40 responders, of whom 22 (73%) demonstrated complete resolution of mucosal ulceration. Patients with growth potential (Tanner 1/2 at induction) demonstrated significant improvements in mean height z-score from induction to years 1 and 2 of follow-up (P < 0.001). With infliximab initiation within the first 18 months after diagnosis, mean height z-score normalized to 0 after 3 years.
  
  
  CONCLUSIONS
  These data demonstrate sustained effectiveness of infliximab in children and adolescents with luminal CD. Durability of response is increased by concomitant immunomodulation. Clinical response is associated with enhanced linear growth, particularly when therapy is initiated early.
authors.affiliation: *Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, University of Toronto, Toronto, ON, Canada; †SickKids Inflammatory Bowel Disease Center, The Hospital for Sick Children, Toronto, ON, Canada; and ‡Cell Biology Program, Research Institute and the Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Church
authors.forename: Jack
authors.initials: J
authors.lastname: Guan
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Walters
authors.forename: Karen
authors.initials: K
authors.lastname: Frost
authors.forename: Amit
authors.initials: A
authors.lastname: Assa
authors.forename: Aleixo M
authors.initials: AM
authors.lastname: Muise
authors.forename: Anne M
authors.initials: AM
authors.lastname: Griffiths
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D015331:Cohort Studies; D003424:Crohn Disease / Q000175:diagnosis* / Q000188:drug therapy*; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006128:Growth / Q000187:drug effects; D006801:Humans; D000069285:Infliximab; D007413:Intestinal Mucosa / Q000187:drug effects; D008297:Male; D012074:Remission Induction; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D012737:Sex Factors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000069285:Infliximab