Before starting azathioprine in Crohn’s disease, which enzyme activity should be tested to avoid toxicity?

• A. TPMT
• B. CYP450
• C. G6PD
• D. BRCA1

Answer: (A)

Understanding how the body processes thiopurines is essential here. Azathioprine is converted to 6-mercaptopurine, and a key enzyme, thiopurine S-methyltransferase (TPMT), inactivates the active thioguanine metabolites. If TPMT activity is low or absent, these toxic metabolites accumulate, leading to severe bone marrow suppression and other toxic effects.

Testing TPMT activity or TPMT genotype before starting azathioprine lets you tailor the dose to the patient’s metabolism. If TPMT activity is normal, you can start with the standard dose. If activity is reduced, you should start at a lower dose and monitor closely. If TPMT activity is very low or absent, you generally avoid thiopurines or use a substantially reduced dose with careful monitoring.

Other enzymes listed don’t drive azathioprine toxicity in the same way. CYP450 is not the main determinant for thiopurines, G6PD deficiency relates to hemolysis with other drugs, and BRCA1 is unrelated to thiopurine metabolism.