Build a precision-prescribing plan for a child starting azathioprine — OSCE

Candidate brief

You have eight minutes to build a precision-prescribing plan for a ten-year-old starting azathioprine for Crohn disease. Use a structured approach: name the tests to order, defend the action a TPMT poor-metaboliser result demands, plan the monitoring, and communicate the result and the plan to the family in plain language. [1]

Key teaching and decision objectives

Name the tests and why together. Order thiopurine methyltransferase, TPMT, and NUDT15 genotype together, because either gene can cause thiopurine toxicity and their effects are additive — a 2024 multiethnic study confirmed that combined TPMT and NUDT15 deficiency produces the most severe thiopurine toxicity. Pair the genotypes with a baseline full blood count and liver enzymes so the monitoring curve starts from a known point. The genotype is a once-in-a-lifetime result, so it must be recorded in a place the next prescriber finds and flagged on the chart. [1] [11]

Defend the poor-metaboliser action. A TPMT poor metaboliser carries two loss-of-function copies and clears the active thioguanine nucleotides slowly, so they accumulate and suppress the marrow. The 2018 CPIC update recommends avoiding a standard starting dose. The safe options are to start at a greatly reduced dose — about 10 per cent of standard — under intensive full-blood-count monitoring, or to choose an alternative immunosuppressant such as mycophenolate or a biologic with the gastroenterology team. The child still has Crohn disease, so the question is how to treat safely, not whether to treat. [1]

Plan the monitoring. Check a full blood count within the first one to two weeks, then on a structured schedule, watching for falling neutrophils and rising transaminases. Wait for the NUDT15 result before committing to a final dose, because an additive poor-metaboliser result at both genes raises the risk further. Document the genotype, the chosen dose, and the reason permanently on the chart and in the family medicines record. [1]

Communication to the family

To the family (plain language): "Your daughter has Crohn disease, which is an inflammation of the bowel, and we treat it with a medicine called azathioprine that calms the immune system down. Before she starts, we checked two of her genes, because some people carry a version that makes this medicine build up in the body and cause a low blood count. Your daughter's result shows she carries that version, so the standard dose would be too much for her. The good news is we can still treat her safely — we will use a much smaller dose and check her blood count very closely, or we can choose a different medicine that does not carry this risk. This result is permanent, so we will write it in her record and give you a copy, because it will be useful for any future prescriptions." [1]

Marking domains

• Clinical reasoning (30 per cent): names TPMT and NUDT15 together; defends the poor-metaboliser action; recognises the additive risk while the NUDT15 result is pending.
• Decision-making (25 per cent): avoids the standard starting dose; chooses a greatly reduced dose or alternative; plans structured full-blood-count monitoring.
• Communication to the family (25 per cent): explains the result and the change of plan in plain language; offers the written record; avoids jargon.
• Safety and follow-through (20 per cent): documents the genotype and reason permanently; flags the chart; arranges the review date; recognises the result-filed-but-not-acted-on failure. [1] [11]