A 28-year-old woman with established Crohn's disease (ileocolonic, moderate activity) is on azathioprine 2.5 mg/kg/day. She continues to have 4–5 loose stools/day, CRP 28 mg/L, and fecal calprotectin 620 µg/g. She is thiopurine methyltransferase (TPMT) normal. The best escalation is:

• A Increase azathioprine dose to 3.5 mg/kg
• B Switch to exclusive enteral nutrition
• C Add methotrexate instead
• D Add anti-TNF (infliximab or adalimumab) — combination therapy ✓

Explanation

In Crohn's disease inadequately controlled on thiopurine monotherapy, combination therapy with an anti-TNF agent (infliximab or adalimumab) plus the thiopurine achieves higher remission rates than either agent alone (SONIC trial: combination vs infliximab vs azathioprine; combination showed highest corticosteroid-free remission). This is the standard of care for moderate-to-severe active Crohn's on failing thiopurine. Methotrexate is an alternative to azathioprine but not superior; simply increasing azathioprine dose without adding biologic is unlikely to achieve mucosal healing.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.