P104 a Nationwide Audit of Adalimumab Use and Safety in Children With Crohn's Disease

Abstract

Poster Communications 23 of markers for effector (interferon gamma, IFNg, and IL-5) and regulatory (FOXP3 and GC-induced tumour necrosis factor receptor, GITR) T-cells. Patient's serum was added to the culture of peripheral blood mononuclear cells isolated from healthy donors (called target cells). The effect of patient's serum on target cells was analysed prior to GC and two weeks later in 19 children with inflammatory bowel disease. Results: A decrease in the GITR (p = 0.050 and 0.005 for unstimulated and PHA-stimulated cells, respectively) and FOXP3 (p = 0.033 for unstimulated cells) expression, and secretion of IFNg (p = 0.017 for unstimulated; p = 0.006 for PHA-stimulated cells) in the target cells was induced by patient's serum during GC therapy. The decrease in the secrection of IFNg paralleled the decrease in erythrocyte sedimentation rate (r = 0.496, p = 0.043). There was a negative correlation at two weeks with target cell secretion of IFNg and disease activity (r = 0.706, p = 0.002). There were no statistically significant changes in the mRNA levels of studied cytokines or transcription factors in PBMC derived from the IBD patients before and at two weeks of GC. Conclusion: Our findings suggest that GC response could be monitored at individual levels by studying the effect of patient's serum on signalling pathways of target immune cells. Background: Infliximab has widely demonstrated its efficacy in the treatment of pediatric inflammatory bowel disease (IBD). Nevertheless, several risks are associated with this therapy. Objectives: To assess long-term clinical serious adverse events (SAE) of infliximab in a pediatric population. Methods: We retrospectively analysed the clinical SAE occurring in pediatric patients treated with infliximab for an IBD, over a period of 7 years (Dec. 1999 to May 2007), in a tertiary care center. Results: 73 patients (mean age: 14.1 years) received a total of 887 infliximab infusions (median: 10/patient), with a median follow-up of 23 months. SAE occurred in 33% of patients, and in 5% of all infusions. Acute and delayed infusion reactions occured in 5 of the 73 patients (6.8%) respectively in each group. Some SAE had never been described in children (drug-induced systemic lupus; seizures). A severe toxic drug-induced eruption was noted in one patient. 16/73 patients (22%) developed 27 severe infections. Among these were noted 8 gastrointestinal infections, 14 skin infections (including 2 zona), 2 respiratory tract infections, 1 neck abcess, 1 catheter-related sepsis and 1 hepatitis B. All of these SAE lead to treatment interruption in 10 patients (13.7%). None was lethal. Conclusion: This study, original through the length of follow-up and the important number of infusions per patient, shows a good overall long-term tolerance of infliximab. SAE, notably infections, are more frequent than in adults. This suggests that infliximab therapy should be reserved to severe pediatric IBD. Background: Adalimumab (ADA) has proven efficacy in RCT in adults but not children with refracto...