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P510 Infliximab in the very young: it is all about the dosing – a multi-centre study

M. Jongsma*1, D. Winter1, H. Huynh2, L. Norsa3, S. Hussey4, K-l. Kolho5, J. Bronsky6, A. Assa7, S. Cohen8, R. Lev-Tzion9, S. van Biervliet10, T. de Meij11, D. Shouval12, E. Wine2, V. Wolters13, A. Christiaens14, C. Martinez-Vinson15, L. de Ridder1

1ErasmusMC-Sophia Children's Hospital, Pediatric Gastroenterology, Rotterdam, The Netherlands, 2Edmonton Pediatric IBD Clinic, Pediatric Gastroenterology and Nutrition, Edmonton, Canada, 3Hopital Necker-enfants-malades, Pediatric Gastroenterology, Paris, France, 4Our Lady's Children's Hospital and RSCI, Pediatric Gastroenterology, Dublin, Ireland, 5Children's Hospital Helsinki, Pediatric Gastroenterology, Helsinki, Finland, 6University Hosptital Motol, Pediatric Gastroenterology, Praque, Czech Republic, 7Schneider Chidren's Hospital, Pedriatric Gastroentrolgy, Tel Aviv, Israel, 8Dana-Dwek Children's Hospital, Pediatric Gastroenterology, Israel, Israel, 9Shaare Zedek Medical Center, Pediatric Gastroenterology, Jerusalem, Israel, 10Universitair Ziekenhuis Gent, Pediatric Gastroenterology, Gent, Belgium, 11VU Medical Center, Pediatric Gastroenterology, Amsterdam, The Netherlands, 12Sheba Medical Center, Pediatric Gastroenterology, Tel Aviv, Israel, 13Utrecht Medical Center, Wilhelmina Children's Hospital, Pediatric Gastroenterology, Utrecht, The Netherlands, 14Universitair Kinderziekenhuis Brussel, Pediatric Gastroenterology, Brussel, Belgium, 15Hopital Robert Debré, Pediatric Gastroenterology, Paris, France

Background

Infliximab (IFX) is administered intravenously using weight-based dose (5 mg/kg) in paediatric and adult inflammatory bowel disease (IBD) patients. However, previous IFX pharmacokinetic (PK) data suggest this results in lower mean serum IFX concentrations in paediatric compared with adult CD patients, especially in young patients. We hypothesise that young children need a more intensive treatment regimen than the current weight-based dose administration.

Aim:

To assess IFX PK, based on existing therapeutic drug monitoring (TDM) data in a population of paediatric IBD patients below age of 10 and to compare these to paediatric IBD patients above age of 10.

Methods

TDM data were collected retrospectively in 15 European and Canadian centres. Children treated with IFX between 2004–2016 were included, if IFX was started as IBD treatment below 10 year and PK data were available. These data were compared with a control group of paediatric IBD patients above age of 10 with PK data of IFX treated paediatric IBD patients in the Erasmus MC-Sophia Children’s Hospital.

Results

One-hundred and sixty paediatric IBD patients were eligible for the study (110 < 10 year; 50 >10 year). Median age IFX treatment was started was 8.3 years [IQR 6.9–8.9] in the young patients (YP), in the older patient (OP) group this was 14.3 [IQR 12.6–15.6]. In 49% of the YP trough levels were below therapeutic range (<3 μg/ml) at 14 weeks. The median interval between IFX infusions was significantly shorter (median interval days 49[39–56] vs. 56[55–56]; p < .001), while the dose (median dose 8 [5–10] mg/kg vs. 5 [5–8.5] mg/kg; p = 0.013) was significantly higher in the YP than OP at 1 year of scheduled IFX maintenance treatment. Moreover, significantly more YP developed antibodies to infliximab (ATI) during follow-up (44% in YP vs. 8.7 in OP, p = 0.004) compared with the OP group, while overall duration of response to IFX was not significantly different between both age groups (after 2 years 53%(n = 29) in YP vs. 63%(n = 26) in OP; p = 0.24).

Conclusion

To achieve therapeutic IFX trough levels in young paediatric IBD patients (<10 years) a more intensive treatment schedule is required. Sub therapeutic IFX levels may be the explanation for development of more ATI’s in young patients compared with the older ones. Despite more ATI formation, duration of IFX therapy was comparable for both age groups. IFX dosing in YP is frequently suboptimal. We recommend to start with a higher dose IFX and an induction schedule with shorter intervals between infusions, beside use of early TDM to further personalise IFX treatment in young IBD patients.