P410 Has body composition any effect on thiopurine level in IBD?

• Published in: Journal of Crohn's and colitis Vol. 12; no. supplement_1; p. S312
• Main Authors: Milassin, Á, Szántó, K, Fábián, A, Bor, R, Farkas, K, Bálint, A, Rutka, M, Földesi, I, Szijártó, A L, Mezei, Z A, Bubán, T, Nagy, F, Szepes, Z, Molnár, T, Palatka, K
• Format: Journal Article
• Language: English
• Published: UK Oxford University Press 16-01-2018
• ISSN: 1873-9946; 1876-4479
• DOI: 10.1093/ecco-jcc/jjx180.537

Abstract
Background
Thiopurines are the most commonly used immunosuppressive therapies in mild-to-moderate IBD. Azathioprine (AZA) is a prodrug, metabolised in 6-thioguanine (6-TG), which has therapeutic effect and 6-methylmercaptopurine (6-MMP), which causes toxic side-effects. Dosage of thiopurines should start gradually, later based on current recommendations dosage, has to be 2–2.5 mg/kg. The effect of body composition on 6-TG level was never been studied. Therapeutic concentration of 6-TG is between 235 and 450 pmol/8 × 108 red blood cell count (RBC). Our aim was to evaluate thiopurine blood level’s connection with weight, body-surface area and different body composition parameters measured by bioelectrical impedance analysis.
Methods
This is a cross-sectional study involving 26 IBD patients (7 Ulcerative Colitis, 19 Crohn’s Disease). Thiopurine metabolite blood level was measured with high-performance liquid chromatography (HPLC) and body composition analysis was performed with bioelectrical impedance analysis.
Results
Patients involved in this study received immunosuppressive therapy in a mean 5.3 years and they have been diagnosed with IBD in a mean 10.3 years. In one case the therapy was 6-MP (75 mg) and in the other cases AZA (50–200 mg). Concommitant therapy was given in 20 cases (77%): 5-ASA 1 (3.8%), cyclosporine 1 (3.8%), biological therapy 12 (46%), steroid plus 5-ASA 2 (7.7%), steroid plus anti TNF agents four cases (15.4%). Considering patients’ weight seven patients (27%) were overweight, 2 (7.7%) patients were underweight. Therapeutic concentration of 6-TG was found in 23 patients (88.5%), they received AZA for a mean 4.3 years. Three patients (11.5%) has lower blood 6-TG level, they received AZA for an average of 14.3 years. The level of AZA metabolite 6-TG correlated with both body weight-based and body-surface area-based AZA doses (p = 0.005 and p = 0.011,, respectively). However, no correlation was found with any of the investigated body composition parameters (total body water, intra-, extracellular water, sceletal muscle mass, body fat mass).
Conclusions
Our study revealed that body composition parameters have no effect on the active AZA metabolite blood level. Therefore, there is no need to modify the current, well-tried dosing scheme of AZA.