Conference paper

Editor list: Cutolo, M

Publication year: 2006

Pages: 477-491

Journal: Annals of the New York Academy of Sciences

Volume number: 1069

ISSN: 0077-8923

ISBN: 1-57331-593-1

DOI Link: https://doi.org/10.1196/annals.1351.048

Conference: 3rd International Conference on Neuroendocrine Immune Basis of the Rheumatic Diseases

Publisher: Wiley

Title of series: Annals of the New York Academy of Sciences

Abstract: 
As azathioprine is one of the standard immunosuppressive drugs used for treatment of patients with different chronic inflammatory diseases, the effect of the azathioprine metabolizing enzyme thiopurine methyltransferase (TPMT) activity on incidence of adverse events (AE) was examined. In addition, potential correlations between the concentration of the azathioprine metabolite 6-thioguanine nucleotide (6-TGN) in erythrocytes (RBC) and inflammatory disease activity as well as hematological AE were investigated. TPMT activities were investigated prospectively in 139 patients (35 mate, 104 female) with chronic inflammatory diseases [systemic lupus erythematosus (SLE, 38), progressive systemic sclerosis (PSS, 13), Wegener's granulomatosis (4), rheumatoid arthritis (RA, 5), and other chronic inflammatory diseases (79)]. In addition, 6-TGN concentrations were investigated in a second cohort of 58 patients (17 patients with SLE, 5 with PSS, 5 with vasculitides, 4 with undifferentiated connective tissue diseases, 1 with dermatomyositis, 1 with Sjogren's syndrome, 1 with RA, 20 with Crohn's disease, and 4 with ulcerative colitis) prior to and during therapy with azathioprine. The distribution of activities of TPMT in 139 patients showed a normal Gaussian distribution in the Caucasian population. Within the group of 96 patients taking azathioprine, known azathioprine-related AE could be observed: minor AE (sickness, rash, and increase in cholestasis parameters) in 11 patients (11.4%), and severe AE (bone marrow toxicity) in 7 patients (7.3%). Below a "cutoff" value of 11.9 nmol/mL REC x h of TPMT activity, AE were significantly more frequent. In the second cohort of patients, no significant correlations could be observed between 6-TGN concentrations and parameters of disease activity. Reduced activity of TPMT in patients with chronic inflammatory diseases requiring immunosuppressive therapy with azathioprine, especially below a distinct cutoff, appears to inherit a substantial risk for development of AE.

Harvard Citation style: Schedel, J., Goedde, A., Schuetz, E., Bongartz, T., Lang, B., Schoelmerich, J., et al. (2006) Impact of thiopurine methyltransferase activity and 6-thioguanine nucleotide concentrations in patients with chronic inflammatory diseases, Annals of the New York Academy of Sciences, 1069, pp. 477-491. https://doi.org/10.1196/annals.1351.048

APA Citation style: Schedel, J., Goedde, A., Schuetz, E., Bongartz, T., Lang, B., Schoelmerich, J., & Mueller-Ladner, U. (2006). Impact of thiopurine methyltransferase activity and 6-thioguanine nucleotide concentrations in patients with chronic inflammatory diseases. Annals of the New York Academy of Sciences. 1069, 477-491. https://doi.org/10.1196/annals.1351.048