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P561. Anti-TNFalpha drug level measurements in IBD patients

M. Rekvig1, M. Gedde Dahl1, J. Bratlie1, N. Bolstad2, B. Moum3, J. Jahnsen4, K.E.A. Lundin1, 1Oslo University Hospital Rikshospitalet, Gastroenterology, Oslo, Norway, 2Oslo University Hospital Radiumhospitalet, Biochemistry, Oslo, Norway, 3Oslo University Hospital Ullevål, Gastroenterology, Oslo, Norway, 4Akershus University Hospital, Gastroenterology, Oslo, Norway

Background

For IBD patients treated with anti-TNFalpha drugs, several studies report a relationship between drug serum levels and efficacy. Optimal therapeutic levels for TNF-inhibition is often considered 5–12 ug/mL for adalimumab and trough level 2–7 ug/mL for infliximab, but these are not well evidence based. Increasingly, drug level measurements are requested by clinicians and we have done this as part of a study.

Methods

All patients receiving therapy with adalimumab or infliximab in IBD outpatient clinics in Norway 2011–2013 were invited to participate. After informed consent a serum sample were collected together with a brief clinical report. Drug concentrations were measured at out-patient follow-up irrespective of time of administration for patients treated with adalimumab and just before the next infusion for patients treated with infliximab (trough level). Analysis were preformed using a proprietary ELISA adapted from Ternant et al (Ther Drug Mon 2006). Reproducibility tests were preformed. We analysed 610 samples from 420 patients for adalimumab and 2336 samples from 751 patients for infliximab. Hence, for most patients several analyses were preformed along the treatment course. The clinicians were free to make individual dose adjustments or not based on the results of the analysis.

Results

For adalimumumab, 41% of the measurements were below 5 ug/mL (Figure 1A - measurements left to dotted line). For infliximab, 28% of the measurements were below 2 ug/mL and 18% above 8 ug/mL (Figure 1B - samples outside the dotted square).

For most patients, we analysed drug concentrations consecutively along the treatment course. For infliximab, the proportion of patients within the range 2–7 ug/mL increased from 47% to 59% from the first measurement to the sixth measurement (Figure 2).

Figure 1. All measurements. Adalimumab N = 610, Infliximab N = 2336.

Figure 2. Infliximab drug serum concentration at 1st and 6th measurement. The proportion of samples in range 1–5 ug/mL increases, while proportion of samples below 0.3 ug/mL and above 8 ug/mL (dotted circles) declines after repeated sampling.

Conclusion

In a large cohort of unselected IBD patients, a substantial proportion of the patients have drug serum levels we believe is too low for the drug to be effective or above what is necessary. Repeated measurements is associated with a higher proportion within what we believe is the therapeutic level. Routinely serum drug measurement may therefore be a profitable clinical tool when optimizing anti-TNF treatment.