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

Abstract

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. Method(s): 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. Result(s): Therapeutic concentration of 6-TGN was detected in 50 patients (78%). Mean concentration was 425; the range was 248-797 pmol/8 x 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(s): 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.