Human antichimeric antibody in children and young adults with inflammatory bowel disease receiving infliximab

J Pediatr Gastroenterol Nutr. 2004 May;38(5):502-8. doi: 10.1097/00005176-200405000-00008.

Abstract

Introduction: Pediatric studies on immunogenicity of infliximab have not been published. The aim of the study was to evaluate the prevalence of human antichimeric antibody (HACA), relationship to infusion reactions (IR), and the role of concomitant immunomodulatory therapies.

Methods: An inflammatory bowel disease (IBD) database was queried, and a retrospective review of patients who had HACA performed was undertaken.

Results: HACA was conclusively determined in 34 patients with IBD (14 male, Crohn disease/ulcerative colitis: 30/4), median age 14.8 years (range, 6.4-22.5 years). Twenty-nine (85.3%) patients were receiving immunomodulatory therapy. A total of 234 infliximab infusions were administered (mean, 6.9; range, 1-26). HACA was detected in 12 (35.3%) patients. IR occurred in 8 (23.5%) patients. HACA-positive patients had a higher proportion of infusions associated with IR than did HACA-negative patients (P < 0.01). HACA levels > or =8.0 microg/mL were more likely to be associated with IR (P = 0.03). Levels of > or = 8.0 microg/mL were more common in patients who had an average interval between infliximab infusions of 8 weeks or less (P = 0.04). Concomitant immunomodulatory therapy was associated with a lower risk of developing HACA (P = 0.02) and lower titer of HACA (P = 0.04). Patients did not have HACA at a greater rate when there was an extended interval (more than 12 weeks) between infliximab infusions (P = 0.89).

Conclusions: In children and adolescents with IBD, HACA formation is related to IR and to the duration of response to treatment. Immunomodulatory agents seem to have a protective role against development of HACA or high titers of antibodies. The interval between infusions does not influence the development of HACA.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / adverse effects
  • Adjuvants, Immunologic / therapeutic use*
  • Adolescent
  • Adult
  • Antibodies / blood*
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Child
  • Databases, Factual
  • Drug Hypersensitivity / blood
  • Drug Hypersensitivity / epidemiology
  • Drug Hypersensitivity / etiology
  • Female
  • Humans
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / immunology*
  • Infliximab
  • Infusions, Intravenous
  • Male
  • Medical Records
  • Philadelphia / epidemiology
  • Prevalence
  • Retrospective Studies

Substances

  • Adjuvants, Immunologic
  • Antibodies
  • Antibodies, Monoclonal
  • Infliximab