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: 3.67). 02/2006; 118(1):11-9. DOI: 10.1016/j.clim.2005.07.010
Source: PubMed


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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    • "Several mild side effects have been observed during IFX infusion, such as fever, chill, rash, pruritus, and dyspnea. No severe adverse events were seen in our study, which is different from earlier reports of infections, malignancy, and deaths [37] [39] [40]. The reactions are attributed to systemic immune response, susceptibility genetic background, or environment factors. "
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    ABSTRACT: This study was undertaken to evaluate the efficacy of infliximab (IFX) in treatment of Crohn's disease (CD) patients. 106 CD patients were undergoing treatment with IFX from five hospitals in Shanghai, China. Clinical remission to IFX induction therapy was defined as Crohn's disease activity index (CDAI) < 150. Clinical response was assessed by a decrease in CDAI ≥ 70, and the failure as a CDAI was not significantly changed or increased. Ten weeks after therapy, 61 (57.5%) patients achieved clinical remission, 17 (16.0%) had clinical response, and the remaining 28 (26.4%) were failed. In remission group, significant changes were observed in CDAI, the Simple Endoscopic Score for Crohn's Disease (SES-CD), and serum indexes. Patients with short disease duration (22.2 ± 23.2 months) and luminal lesions showed better effects compared to those with long disease duration (71.0 ± 58.2 months) or stricturing and penetrating lesions. IFX markedly downregulated Th1/Th17-mediated immune response but promoted IL-25 production in intestinal mucosa from remission group. No serious adverse events occurred to terminate treatment. Taken together, our studies demonstrated that IFX is efficacious and safe in inducing clinical remission, promoting mucosal healing, and downregulating Th1/Th17-mediated immune response in short course CD patients with luminal lesions.
    Mediators of Inflammation 04/2015; 2015:793764. DOI:10.1155/2015/793764 · 3.24 Impact Factor
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    • "A number of reactions have been described in patients receiving infliximab. The majority of reactions are not IgE-mediated, but due to direct activation of mast cells,54 they can be pretreated with steroids, antihistamines, and antipyretics. Also, it has been observed that loading in three separate doses given at week 0, 2, and 6 is less immunogenic than administering a single high-loading dose. "
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    ABSTRACT: Anaphylaxis is an increasingly prevalent problem in westernized countries. Therefore, it is of utmost importance that the increasing numbers of patients at risk for anaphylaxis receive proper education on the etiology and risk factors as well as appropriate treatment of anaphylaxis with epinephrine. The physician's role is crucial in order to educate the patients and care takers on effective measures to prevent anaphylaxis and empower them to take charge of early recognition and proper management of an anaphylactic reaction to prevent poor outcomes. This review summarizes the clinical presentation, triggers, avoidance, and management of anaphylaxis.
    Journal of Asthma and Allergy 07/2014; 7(7):95-104. DOI:10.2147/JAA.S48611
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    • "There appears to be some correlation between the rates of secondary loss of response and the acquisition of antibodies to infliximab, in both adults and children [35, 46, 47]. The rate of secondary loss of response may be reduced with scheduled maintenance therapy and the use of concurrent immunomodulators such as methotrexate or thiopurines; however, these should be used with caution in children, due to concerns about the possible risks for malignancy (see the section “Adverse Effects,” below) [46, 48, 49]. "
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    ABSTRACT: Crohn's disease affects increasing numbers of children worldwide. Generally, childhood-onset disease runs a more severe course than in adults and has a greater impact on quality of life. Therapy in children must take account of a different set of risks for toxicity compared to adults, but also to their longevity. Biologic drugs present remarkable advantages in terms of disease control for children, especially in those whose disease cannot be controlled with conventional therapies, but their long-term risks are still being assessed. Data regarding biologic use in children is limited and mostly amounts to case series, but results have been promising, both in terms of controlling disease activity and improving growth parameters. Adverse reactions are infrequent in the short term, but loss of response is a long-term problem, particularly in children. More information is needed about very long term risks. Infliximab and adalimumab are the most studied agents in children, while there is relatively limited data on certolizumab and natalizumab. Further collection of data on these agents is still needed, but this should not restrict access to these agents for children in whom no other agent is effective.
    Gastroenterology Research and Practice 11/2011; 2011:287574. DOI:10.1155/2011/287574 · 1.75 Impact Factor
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