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OP11. Individualised infliximab treatment using therapeutic drug monitoring: A prospective controlled Trough level Adapted infliXImab Treatment (TAXIT) trial

N. Vande Casteele1, G. Compernolle1, V. Ballet2, G. Van Assche2, A. Gils1, S. Vermeire2, P. Rutgeerts2

1Katholieke Universiteit Leuven, Laboratory for Pharmaceutical Biology, Belgium; 2University Hospitals Leuven, Department of Gastroenterology, Leuven, Belgium

Background: Loss of response to infliximab (IFX) is seen in up to 50% of IBD patients. This is often a result of antibody formation and subsequent low infliximab concentrations (trough levels). Loss of response is managed clinically by decreasing the interval between infusions or increasing the dose. We hypothesised that sustained good anti‑TNF trough levels are associated with a better long term outcome. Aim: To investigate the value of individualised treatment with IFX based on therapeutic drug monitoring in a randomised controlled trial.

Methods: 270 consecutive IBD patients on IFX maintenance therapy were randomised to dosing based on IFX trough levels (TLI) (group1: TLI kept in a window between 3 and 7 µg/ml) or dosing and optimisation based on clinical symptoms (group 2). Before randomisation, trough levels were first optimised to have a baseline TLI between 3 and 7 µg/ml. The primary endpoint is defined as clinical and biological (CRP <5 mg/l) remission rates at one year after randomisation. TLI (expressed in µg/ml) and antibodies to infliximab (ATI; expressed in µg/ml equivalents) were measured with an in-house developed ELISA. We here report on the results of the optimisation phase.

Results: In the total cohort of patients (n = 270) in clinical remission, 117 patients (43%) had a TLI between 3 and 7 µg/ml and needed no dose adjustment, 71 patients (26%) had a TLI higher than 7 µg/ml and in these patients the dose of IFX was reduced. 59 patients (22%) had a detectable TLI lower than 3 µg/ml and 23 patients (9%) even had undetectable TLI of which 17 patients (77%) were ATI positive: (median; IQR) (5.92; 2.76–7.68 µg/ml eq.). In these patients the dose of IFX was increased to reach the target level. In 6 patients IFX therapy was discontinued due to absent TLI and ATI >8 µg/ml eq. and they were excluded from the randomised study. Patients with TLI <3 µg/ml had a significantly higher CRP (2.75; 1.03–7.53 mg/l) compared to patients with a TLI between 3 and 7 µg/ml (1.45; 0.60–3.28 mg/l) (P-value = 0.001) and patients with a TLI >7 µg/ml (1.20; 0.60–4.80 mg/l) (P-value = 0.01).

Conclusions: The results of this optimisation phase of the TAXIT trial show that in this large cohort of patients in remission under treatment with maintenance infliximab only 43% have optimal TLI. In the others dose adjustment was carried out. 9% of the patients have undetectable TLI despite staying in remission. The current controlled study will show whether long term adjustment of treatment based on IFX levels is a superior strategy.