Clinical and biological consequences of immunization to infliximab in pediatric Crohn's disease

Laboratoire d'Immunologie, Université René Descartes-Paris5, INSERM U580, Hopital Necker Enfants Malades, 149 rue de Sèvres, 75015 Paris, France.
Clinical Immunology (Impact Factor: 3.99). 02/2006; 118(1):11-9. DOI: 10.1016/j.clim.2005.07.010
Source: PubMed

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.

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