title: Clinical and biological consequences of immunization to infliximab in pediatric Crohn's disease.
abstract: Tumor necrosis factor (TNF)-alpha plays a critical role in the initiation and progression of Crohn's disease, a chronic inflammatory disorder of the gastrointestinal tract. Infliximab, a chimeric monoclonal antibody blocking TNF-alpha, has proven effective as an induction and maintenance therapy for refractory Crohn's disease in adult and pediatric patients. However, infliximab therapy induces the appearance of neutralizing anti-infliximab antibodies. In the pediatric cohort, we analyzed (n=28) sensitization occurred in 35.7% patients and was associated with a loss of response to maintenance infusions. In two patients presenting high titers of anti-infliximab antibodies, severe infusion reactions were observed, possibly IgE-mediated, precluding further use of the medication. Serum concentrations of TNF-alpha and infliximab were influenced by the presence of anti-infliximab antibodies. We propose that surveillance of circulating infliximab and/or TNF-alpha concentration during maintenance therapy represents an indirect but reliable method to monitor anti-infliximab immunization.
authors.affiliation: Laboratoire d'Immunologie, Université René Descartes-Paris5, INSERM U580, Hopital Necker Enfants Malades, 149 rue de Sèvres, 75015 Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Candon
authors.forename: Alexis
authors.initials: A
authors.lastname: Mosca
authors.forename: Frank
authors.initials: F
authors.lastname: Ruemmele
authors.forename: Olivier
authors.initials: O
authors.lastname: Goulet
authors.forename: Lucienne
authors.initials: L
authors.lastname: Chatenoud
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cézard
mesh_terms: D000293:Adolescent; D000888:Antibodies, Anti-Idiotypic / Q000097:blood / Q000378:metabolism; D019138:Antibodies, Blocking / Q000097:blood / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology* / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology*; D005260:Female; D006801:Humans; D007114:Immunization / Q000009:adverse effects; D007223:Infant; D000069285:Infliximab; D008297:Male; D012189:Retrospective Studies; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D000888:Antibodies, Anti-Idiotypic; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab