Workshop 3

Thiopurine methyltransferase assessment and azathioprine treatment

Dr Loretta Ford & Dr Jonathan Berg

Azathioprine is widely used as an immunosuppressant and is metabolised in part by the enzyme thiopurine S-methyltransferase (TPMT). TPMT is subject to genetic variation with 0.3% patients having deficient enzyme activity and a further 11% having low TPMT activity.

Patients with deficient TPMT activity are at most risk of developing severe myelosuppression when given azathioprine at standard doses, and there have been recorded deaths. Patients with low levels of TPMT activity are at risk of thiopurine induced toxicity. Alteration of the dose of azathioprine given based on TPMT activity status is not straightforward.

The issues that will be discussed will include:

• Is there an evidence base for assessing TPMT status prior to treatment?
• Is there a cost benefit based on identifying patients with deficient TPMT activity alone?
• Assessing TPMT status -phenotyping or genotyping?
• TPMT service – what should the laboratory standards be?
• Are there clinical guidelines for dose alteration based on TPMT status?

The workshop takes place on a narrowboat gliding around the city centre canals.

Assessment of TPMT status is often quoted as the best example of applied pharmacogenomics, yet the issues are still controversial, as delegates will find out.