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P674 Blood thiopurine level, anti-TNF drug level and body composition parameters in inflammatory bowel diseases patients: a cross-sectional study in a Hungarian IBD centre

K. Szántó1, A. L. Szíjártó2, D. Kata3, I. Földesi3, Z. A. Mezei4, A. Fábián1, A. Bálint1, R. Bor1, K. Farkas1, Á. Milassin1, M. Rutka1, Z. Szepes1, F. Nagy1, T. Bubán5, S. Lovas6, K. Palatka6, T. Molnár1

1University of Szeged, First Department of Medicine, Szeged, Hungary, 2University of Szeged, Department of Medical Physics and Informatics, Szeged, Hungary, 3University of Szeged, Institute of Laboratory Medicine, Szeged, Hungary, 4University of Debrecen, Department of Laboratory Medicine, Debrecen, Hungary, 5University of Debrecen, Department of Internal Medicine, Debrecen, Hungary, 6University of Szeged, 2nd Department of Internal Medicine, Debrecen, Hungary

Background

Clinical data suggest a synergistic effect between thiopurine and anti-tumour necrosis factor (anti-TNF) therapy in IBD. However, azathioprine (AZA) metabolites and biological drug trough levels have not been investigated simultaneously. Furthermore, the effect of body composition on 6-thioguanine nucleotide (TGN) level has never been studied. The aim of the study was to evaluate potential correlation between AZA active metabolite 6-TGN levels and anti-TNF drug (infliximab [IFX] and adalimumab [ADA]) serum trough levels and body composition parameters.

Methods

This was a cross-sectional study involving 98 IBD patients. Patients on maintenance AZA (n = 30) and on IFX+AZA or ADA+AZA combinations (n = 34, 14 ADA, 20 IFX) and activity indices based on pair-matched controls on IFX or ADA monotherapy (n = 34, 14 ADA, 20 IFX) were prospectively enrolled. Thiopurine metabolite blood level was measured with high-performance liquid chromatography (HPLC) and body composition analysis was performed with bioelectrical impedance analysis.

Results

Therapeutic concentration of 6-TGN was detected in 50 patients (78%). Mean concentration was 425; the range was 248–797 pmol/8 × 108 RBC. Antibody formation proved to be significantly lower in patients receiving combined IFX+AZA therapy compared with IFX monotherapy (p = 0.0001). There was no difference in antibody formation between ADA+AZA vs. ADA monotherapy patients. ADA trough levels were significantly higher in patients with ADA+AZA combined vs. ADA monotherapy. In contrast, no difference was found between IFX trough level in patients receiving combined IFX+AZA vs. IFX monotherapy. The level of 6-TGN correlated with body weight-based AZA doses (p = 0.017), however no correlation was found with body surface area-based AZA doses (p = 0.081). Further correlation was shown regarding to body composition parameters such as total body water (r = −0.33, p = 0.011), intra-, and extracellular water (r = −0.325 and −0.334, p = 0.008 and p = 0.008, respectively), skeletal muscle mass (r = −0.326, p = 0.01). No correlation was found with body fat mass (r = −0.091, p = 0.487).

Conclusion

Most of the patients had therapeutic 6-TGN level with body-weight based administration without previous measurement. This is due to our findings that 6-TGN level correlated with body weight-based AZA doses total body water, intra-, extracellular water and skeletal muscle mass. Our data suggest the possible synergistic effect of thiopurine and anti-TNF combination therapy based on the decreased antibody formation among IFX-treated patients and increased anti-TNF drug level regardless of antibody formation in ADA-treated patients. However the small number of the patients requires further investigations.