A 26-year-old woman with Crohn's disease limited to the terminal ileum on azathioprine 2.5 mg/kg/day has persistently elevated CRP and ongoing symptoms. Colonoscopy shows active ulceration with deep linear fissuring. She tests negative for TPMT deficiency. What is the next best step?
- A Switch to methotrexate
- B Start oral budesonide as long-term maintenance
- C Proceed directly to ileocaecal resection
- D Add an anti-TNF agent (infliximab or adalimumab) — combined immunosuppression ✓
Explanation
Active luminal Crohn's disease inadequately controlled on thiopurine therapy warrants escalation to biologic therapy. Anti-TNF agents (infliximab, adalimumab) in combination with azathioprine achieve higher rates of deep remission than either alone (SONIC trial). The combination reduces immunogenicity of the biologic. Methotrexate is an alternative immunomodulator, not an escalation above thiopurines in this scenario. Oral budesonide is for induction in mild-moderate ileocaecal Crohn's, not maintenance of refractory disease. Surgery is reserved for stricturing/penetrating complications or medical failure.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.