Thiopurine methyltransferase screening before azathioprine prescription: a physician survey

In patients treated with azathioprine, deficient thiopurine methyltransferase (TPMT) activity has been associated with haematologic toxicity.

To determine how many Saskatchewan rheumatologists routinely pre-screen TPMT activity before prescribing azathioprine. Further, to retrospectively review TPMT activity levels from pre-screening in one patient cohort.

All rheumatologists practicing in the province of Saskatchewan were surveyed by questionnaire. The questionnaire scrutinized prevalence of routine TPMT screening pre-azathioprine initiation, response to abnormal test results, monitoring frequencies, starting dosages, and attitudes towards potential consensus guidelines or practice standards. For the second objective of this study, health region laboratory database retrieval identified 42 patients who had undergone TPMT phenotype testing within a single rheumatology practice. Chart review of all 42 patients was performed to verify test results.

In a survey of all eleven Saskatchewan rheumatologists, 55% reported routinely pre-screening, compared to 45% who never screen pre-azathioprine. Half of those who pre-screen, report avoidance of azathioprine in both patients with deficiency and those with intermediate activity levels. The majority of respondents indicated they would adjust their practice to conform to future national rheumatology clinical guidelines. A retrospective review in one practice revealed TPMT activity values consistent with deficiency, carrier status, and normal ranges in 2.4%, 21.4%, and 76.2% of patients pre-screened, respectively.

Provincial rheumatologists were divided on the practice of pre-screening TPMT status prior to initiation of azathioprine. Azathioprine may be underutilized by half of those who pre-screen. A need for practice guidelines was recognized by the participants. In this patient group, diminished TPMT activity was observed in 23.8% of those who were tested.