azathioprine. A pilot study

Objective-To study the possible association of purine enzyme activities with response to azathioprine (AZA) treatment in rheumatoid arthritis (RA) and their correlation with parameters of disease activity. Patients and methods--Lymphocyte activities of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT), adenine phosphoribosyltransferase (APRT), purine nucleoside phosphorylase (PNP) and 5'-nucleotidase (5NT), and erythrocyte activities of thiopurine methyltransferase (TPMT) were measured in 14 healthy controls and 36 patients with RA. Eight patients had not previously been treated with AZA. Response to AZA therapy in 28 patients, determined in a prospective trial, was considered good in nine (group 1), insufficient in seven (group 2). In 12 patients AZA was withdrawn because of adverse reactions (group 3). Disease activity parameters were obtained simultaneously with purine enzyme measurements. Purine enzyme levels in the different groups were compared. Results-Levels of SNT activity were significantly lower in patients with RA than in healthy controls. PNP activity was higher in patients with RA not using prednisone compared with those who did and healthy controls. No clear correlation between purine enzyme levels and disease activity parameters was found. 5NT activities were significantly higher in group one than in group three (p = 0-012; a = 0.017), and almost significantly higher than in group two (p = 0 03; a = 0.017). Conclusions-The results indicate that purine enzyme activities in patients with RA differ from healthy controls, are associated with the outcome of AZA treatment and seem not to be associated with disease activity. Our findings may offer a clue to predict the response to AZA therapy in RA. (Ann Rheum Dis 1994; 53: 608-61 1) After conversion to 6-mercaptopurine (6MP) the metabolism of azathioprine (AZA) parallels the endogenous purine pathways. Deficiencies of purine enzymes may reduce efficacy or increase toxicity of AZA. To our knowledge, the relation between purine enzyme levels and response to AZA therapy in patients with RA has not been systematically studied so far. The present study was undertaken to investigate purine enzyme activities in patients with RA and their association with response to AZA therapy. Patients and methods