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P520 Therapeutic drug monitoring in 45 children with inflammatory bowel disease on maintenance infliximab treatment

H. Rolandsdotter1, 2, P. Marits2, 3, U. Sundin3, A.-C. Wikström2, 3, U. Fagerberg2, 4, Y. Finkel1, 2, M. Eberhardson*2, 5

1Sachs’ Children and Youth Hospital, Department of Gastroenterology, Stockholm, Sweden, 2Karolinska Institute, Stockholm, Sweden, 3Karolinska University Hospital, Department of Clinical immunology and Transfusion Medicine, Stockholm, Sweden, 4Vastmanland Hospital Vasteras, Centre for Clinical Research, Vasteras, Sweden, 5Karolinska University Hospital, Centre for Digestive Diseases, Stockholm, Sweden

Background

The anti-TNF antibody infliximab (IFX) is frequently used as maintenance therapy in paediatric inflammatory bowel disease (IBD). However, the role of monitoring trough s-IFX and antibodies towards IFX (ATI) during maintenance treatment remains unclear in children. The aim of the present study was to investigate the trough levels of IFX and the presence of ATI to identify any correlation with inflammatory activity and clinical response in a paediatric IBD cohort.

Methods

We conducted a cross-sectional study of s-IFX in all IFX-treated children with IBD (n = 45, Crohn’s disease [CD] = 32 and ulcerative colitis [UC] = 13) in 2 Swedish counties, Stockholm and Vasteras. The children were on maintenance IFX treatment and had received 4–48 infusions. IFX trough levels and ATI were analysed 1–4 times in each patient using an in-house ELISA assay. ATI could only be analysed when IFX was undetectable. In total, 93 IFX trough level tests were collected. Demographics, concomitant immunosuppression, CRP, ESR, albumin, and the validated clinical activity indices Paediatric UC Activity Index (PUCAI) and Paediatric CD Activity Index (PCDAI) were recorded.

Results

The children received a mean IFX dose of 6.4 ± 1.7 mg/kg with a mean interval of 44.8 ± 11.2 days. The mean s-IFX trough level was 5.2 μg/mL (median 4.5 μg/mL). The trough s-IFX was significantly higher in the samples taken during remission (mean 8.0 μg/mL, median 6.5 μg/mL) as compared with s-IFX in active disease (mean 4.0 μg/mL, median 2.7 μg/mL, p < 0.05). The trough IFX levels displayed a significant correlation with ESR, CRP, and albumin. S-IFX was undetectable in 8 of the patients, none of whom was in remission at the time of the sampling. ATI was positive in all these samples. S-IFX trough levels in patients with monotherapy were lower compared with patients on concomitant azathioprine, however, without reaching statistical significance. Surprisingly, clinical remission (assessed as a composite of clinical activity index, ESR, and CRP) was found only at 30 of the 93 test occasions in these 45 children on maintenance treatment. When comparing the 45 children with an adult population of 79 IBD patients treated with IFX and analysed with the same ELISA assay,1 the mean s-IFX trough levels were significantly higher in the paediatric remission group (8.0 vs 4.1 μg/mL; p < 0.05)., as well as in the active disease group (4.0 vs 1.8 μg/mL, p < 0.05).

Conclusion

S-IFX trough concentration correlated to the clinical response to infliximab in 45 children with IBD and IFX maintenance treatment. In comparison with an adult IBD population on maintenance IFX (previously reported), the paediatric cohort showed higher levels of trough s-IFX.

References

Marits et al. JCC 2014 Aug;8(8):881.