Use of infliximab in the treatment of Crohn's disease in children and adolescents.
BACKGROUND
Crohn's disease is often poorly responsive to conventional therapy with corticosteroids and immunomodulators. A novel chimeric antibody to tumor necrosis factor-alpha, infliximab, has shown utility in the treatment of refractory Crohn's disease in adults.


OBJECTIVE
To evaluate the efficacy of open-label administration of infliximab in children and adolescents with active intestinal Crohn's disease.


METHODS
Chart review of the experience with 19 subjects (mean age 14.4 years, range 9 to 19 years) receiving 1 to 3 infusions of infliximab (5 mg/kg/dose) over a 12-week period for corticosteroid-resistant disease (n = 7) or corticosteroid dependence (n = 12). Disease activity was monitored by physician global assessment and the Pediatric Crohn's Disease Activity Index.


RESULTS
Significant initial improvement (first 4 weeks after infusion) was noted in all subjects, with Pediatric Crohn's Disease Activity Index values decreasing significantly (mean +/- SD, 42.1 +/- 13.7 to 10.0 +/- 5.6, P <.0001). Over the subsequent 8-week period, 8 of 19 treated subjects had worsening of symptoms, although none deteriorated to severe activity. The mean Pediatric Crohn's Disease Activity Index at 12 weeks was 26.8 +/- 16. 4. The mean daily prednisone dosages at baseline, 4 weeks, and 12 weeks were 28 +/- 14 mg, 20 +/- 12 mg, and 8 +/- 12 mg, respectively (P <.01). Adverse effects were noted in 3 patients during infusion (dyspnea, rash) and were self-limited.


CONCLUSIONS
Infliximab is associated with short-term clinical improvement in children and adolescents with severe Crohn's disease. The rapid return of disease activity in some patients suggests that additional dosing strategies may be required. Long-term safety necessitates close monitoring.
Hyams
J S
JS
Departments of Pediatrics, Connecticut Children's Medical Center, Hartford, Connecticut, USA.
Markowitz
J
J
Wyllie
R
R
D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D005765:Gastrointestinal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D000069285:Infliximab; D007262:Infusions, Intravenous; D008297:Male; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab