A 32-year-old woman with Crohn's disease (ileal involvement, CDAI 320) fails to respond to azathioprine plus infliximab (primary non-response). Anti-infliximab antibodies are detected at high titer. The MOST appropriate next step is:
- A Double the infliximab dose to 10 mg/kg
- B Switch to a different anti-TNF agent (adalimumab) given immunogenic non-response to infliximab
- C Add methotrexate as co-immunosuppressant to reduce antibody formation to infliximab
- D Switch to vedolizumab (anti-α4β7 integrin) or ustekinumab (anti-IL-12/23) as non-anti-TNF biologics ✓
Explanation
When primary or secondary loss of response to anti-TNF therapy is driven by immunogenic anti-drug antibodies (ADAs), switching to another anti-TNF agent (adalimumab) can work if ADAs are infliximab-specific with some cross-reactivity. However, with high ADA titres and true primary non-response, switching to a mechanistically distinct biologic (vedolizumab or ustekinumab) is preferable. Vedolizumab (anti-α4β7 integrin) and ustekinumab (anti-IL-12/IL-23 p40) are both approved for moderately-to-severely active Crohn's disease after anti-TNF failure. Dose escalation does not overcome immunogenic non-response. Adding methotrexate could reduce ADA formation if started earlier but cannot reverse established high ADA titres.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.