Ansari, A.; Escudier, M.; Marinaki, A.; Yim, A.; Hirst, J.; Duley, J.; Sanderson, J.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA64
Academic Journal
Background: Deficiency of thiopurine methyl transferase (TPMT) is associated with a high risk of adverse effects on azathioprine (AZA) therapy. Conventionally, AZA is avoided in patients with zero TPMT (1 in 300) and those with heterozygous TPMT deficiency. (1 in 10). Aims: We have studied the outcome of TPMT deficient patients receiving a tailored Iow dose of AZA. Methods: According to a department protocol, patients with zero TPMT were offered treatment with 5% usual dose, heterozygotes with 1 mg/kg AZA. Thioguanine nucleotide (TGN) levels were assayed in a proportion of cases. In addition, a questionnaire was sent to physicians regarding the outcome of patients referred for TPMT assay from outside the author's institution. Results: Two patients with zero TPMT (One CD, one UC) responded to 5% dosing with a prompt and full clinical remission (HBI / Truelove and Witts score). Both have remained in steroid-free remission for two years. TGN levels were very high yet both remained free of myelotoxicity. 26 heterozygotes 12 CD, 7 UC, 2 autoimmune hepatitis, and 5 with oral ulceration were treated. 20 (77%) patients responded to treatment, 1 did not respond and 5 withdrew treatment as a consequence of side effects (19%). TGN levels were variable and did not correlate with response or side effects. Of 92 questionnaires sent, 51 replies were obtained. Of these, only 15 patients started azathioprine at 1 mg/kg. 11/15 (73%) responded to treatment, 2 failed, and 2 withdrew due to side effects. In 36/51 (71%) the requesting physician decided not to use ozathioprine due to the Iow TPMT level. Conclusions: Physicians generally avoid AZA in patients with TPMT deficiency. However, the results of this study show that heterozygous patients respond well to Iow dose AZA. Furthermore, zero TPMT patients can be successfully treated with a very Iow dose of AZA.


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