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Biologic Loss of Response IBD — RACP Adult Medicine MCQ

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ModerateGastroenterology & HepatologyBiologic Loss of Response IBDRACP Adult Medicine

A 62-year-old man with severe Crohn's disease on vedolizumab develops secondary loss of response after 18 months of therapy. His CRP has risen and he has active endoscopic disease. Drug levels show adequate vedolizumab trough levels with no anti-drug antibodies. What is the most appropriate next step?

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Correct answer: E — Switch out of class (to anti-TNF or ustekinumab or risankizumab)

When a patient develops secondary loss of response to a biologic with adequate drug levels and no anti-drug antibodies (pharmacokinetic failure ruled out), this represents pharmacodynamic failure – the drug is present but the mechanism is no longer sufficient. Switching to a different mechanism of action (out-of-class switch) is recommended. Options include anti-TNF (infliximab/adalimumab), ustekinumab (anti-IL-12/23), or risankizumab (anti-IL-23 – recently approved for Crohn's disease). Increasing the dose or adding an immunomodulator is unlikely to overcome pharmacodynamic failure. Within-class switching (to another anti-integrin) is not clinically available.

Reference: eTG – 2025 – Gastrointestinal; ECCO – 2024 – Crohn's Disease Therapeutic Algorithms