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DOP042. Large variation in infliximab trough levels is associated with disease activity in paediatric inflammatory bowel disease

D. Hoekman1, H. Brandse2, T. de Meij3, T. Hummel4, M. Löwenberg2, M. Benninga1, G. D'Haens2, A. Kindermann1, 1Academic Medical Center/Emma Children's Hospital, Department of Paediatric Gastroenterology and Nutrition, Amsterdam, Netherlands, 2Academic Medical Center, Department of Gastroenterology, Amsterdam, Netherlands, 3VU University Medical Center, Pediatric Gastoenterology, Amsterdam, Netherlands, 4Medisch Spectrum Twente, Pediatric Gastoenterology, Enschede, Netherlands

Background

Low serum trough levels (TL) of infliximab (IFX) and the formation of antibodies to IFX (ATI) are associated with the loss of therapeutic response in adults with inflammatory bowel disease (IBD). Until now, paediatric data are scarce. Therefore, we aimed to investigate the association between ATI and IFX TLs, and clinical and biochemical disease activity (DA) in children receiving maintenance treatment with IFX for IBD.

Methods

All children aged <18 years receiving scheduled IFX maintenance treatment for Crohn's disease (CD) or ulcerative colitis (UC) in 3 hospitals in the Netherlands where asked to participate. Prior to two consecutive IFX infusions, IFX TL and ATI were measured. Therapeutic range of IFX was considered 3–7 µg/mL. Furthermore, biochemical DA was assessed by C-reactive protein (CRP) and faecal calprotectin (FC) (Bühlman ELISA). Clinical DA was determined by activity indices PCDAI and PUCAI, for CD and UC, respectively. Clinical remission was defined as a score of <10 for both PCDAI and PUCAI. A score of >30 or ≥65 was considered severe DA for PCDAI and PUCAI, respectively.

Results

Between December 2012 and February 2013 33 patients were included (26 CD, 7 UC), with a median age of 14 years [IQR 12–16]. All TL measurements combined (n = 66), the median IFX TL was 3 µg/mL [IQR 1–6]. Subtherapeutic, therapeutic and supratherapeutic TLs were found in 42.4%, 39.4% and 18.2% of measurements, respectively. ATI were detected in 3 patients but our assay does not allow antibody detection in the presence of drug. Median FC and CRP was 394.5 µg/g and 2.4 mg/L, respectively. At both time points, the majority of patients were either in clinical remission (56.9%) or had mild to moderate clinical DA (41.2%).

At the first measurement, no significant correlation between IFX TL and clinical or biochemical DA was found, although a trend was observed for FC (r = −0.33, p = 0.08) and CRP (r = −0.33, p = 0.06).

At the second measurement, a significant correlation was found between IFX TL and clinical DA grading (r = −0.48, p = 0.01) and FC (r = −0.49, p = 0.01). Patients with therapeutic IFX TLs (≥3 µg/mL) were more likely to be in clinical remission (p = 0.01).

At both measurements, a significant correlation between clinical DA and FC was observed (r = 0.53, p < 0.01; r = 0.50, p = 0.02), whereas no correlation was found between CRP and clinical DA (p = 0.16; p = 0.44).

No difference was found in IFX TLs between children receiving IFX monotherapy or concomitant immunosuppression.

Conclusion

IFX TLs appear to be related to both clinical and biochemical DA (the latter measured by FC), which provides a rationale for therapeutic drug monitoring in children receiving IFX for IBD. Furthermore, a large variation in IFX TLs was found.