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N011. Therapeutic drug monitoring of thiopurine metabolites in patients with inflammatory bowel disease (IBD) in a Dutch peripheral hospital. Indications and therapeutic consequences

R. Theeuwen1, M. Alleman1, S. Abraham1, R. Ong2, M. Vu1, 1Rijnland Hospital, Gastroenterology, Leiderdorp, Netherlands, 2University of Applied Sciences, Epidemiology, Leiden, Netherlands

Background

There are no clear guidelines concerning therapeutic drug monitoring in thiopurine treated IBD patients. This results in conflicting recommendations for metabolite monitoring in routine practice. The aim of this study was to retrospectively identify indications for thiopurine drug monitoring and subsequent therapeutic consequences in IBD patients with thiopurine therapy.

Methods

A patient file study was carried out. All adult IBD patients with established thiopurine treatment between January 2008 to December 2011 were included. Data were collected on indications for drug monitoring, 6-TGN and 6-MMP levels and subsequent treatment strategies.

Results

107 IBD patients were studied. A total of 255 6-TGN and 6-MMP metabolite levels were monitored.

Therapeutic drug monitoring was performed in 27% of the cases because of lack of clinical response, 23% for control after dose adjustment and 14% due to suspicion of toxicity under thiopurine therapy. In 14% of the cases therapeutic drug monitoring was performed because of a low TPMT activity.

Low 6-TGN level in a combination with normal or low 6-MMP level were found in 57% of the measured metabolite levels. 27% of the studied metabolite levels had normal 6-TGN and 6-MMP levels. Normal 6-TGN level in combination with a high 6-MMP level were found in 10% of the measured metabolite levels.

In 65% of the cases the subsequent therapeutic consequences were explainable with the corresponding metabolite levels. Within 30% of the patients with exacerbation complaints and low 6-TGN metabolic results, no therapeutic changes were carried out.

Conclusion

Various indications for therapeutic drug monitoring of thiopurine metabolites were found in this retrospective study. In most cases, monitoring of thiopurine metabolite levels is useful to guide and optimize dosing, to minimize the risk of drug toxicity and to confirm non-compliance.