A 30-year-old woman with Crohn's disease (terminal ileal involvement, CDAI 320, CRP 45 mg/L) has been on azathioprine 2 mg/kg for 6 months with inadequate response. Colonoscopy shows deep ulcers with skip lesions. What is the most appropriate next step per current ECCO and ACG guidelines for moderately-severe luminal Crohn's?
- A Increase azathioprine dose to 3 mg/kg
- B Switch to methotrexate monotherapy
- C Initiate anti-TNF therapy (infliximab or adalimumab), preferably in combination with an immunomodulator to reduce immunogenicity ✓
- D Start oral budesonide 9 mg daily as next step
Correct answer: C. Initiate anti-TNF therapy (infliximab or adalimumab), preferably in combination with an immunomodulator to reduce immunogenicity
Explanation
Failure of an immunomodulator (azathioprine) after 6 months in moderately-severe luminal Crohn's disease is an indication to escalate to biological therapy — anti-TNF agents (infliximab, adalimumab) are first-line biologicals. Combination therapy (anti-TNF + immunomodulator) reduces anti-drug antibody formation and improves durability of response (SONIC trial). Budesonide is appropriate for mild-moderate ileocaecal disease and not for moderate-severe Crohn's with deep ulcers.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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