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Background: About a third of patients with inflammatory bowel disease do not respond to anti-tumour necrosis factor (anti-TNF) therapy, which is challenging. Aim: To review the current data on the two main strategies when facing primary non-response to an anti-TNF agent in inflammatory bowel disease: changing to a second anti-TNF (switching) or to a drug with another mechanisms of action (swapping). Methods: We performed a bibliographic search to identify studies reporting on efficacy of any biologic treatment after primary anti-TNF non-response. Results: The efficacy of a second anti-TNF is lower when the reason to withdraw the first one is primary failure. Nevertheless, switching to another anti-TNF even after primary failure may still be effective in some patients. Both vedolizumab and ustekinumab have generally been shown to be less effective in anti-TNF exposed patients. However, despite primary anti-TNF failure, patients may respond to vedolizumab or ustekinumab in a limited but considerable number of cases. The cause for swapping (primary vs. secondary anti-TNF failure) seems to have limited effect on vedolizumab efficacy. Primary anti-TNF non-response seems to be a clearer predictor of treatment failure for ustekinumab. Unfortunately, the two main strategies to treat specifically a patient with primary non-response to an anti-TNF agent—switching to a second anti-TNF or swapping for vedolizumab/ustekinumab—have not been properly compared. Conclusion: The data reviewed in the present study clearly emphasise the imperative need to carry out head-to-head randomised trials in patients exposed to anti-TNF agents in general, and specifically in those with primary non-response to these agents.

Primary Failure to an Anti-TNF Agent in Inflammatory Bowel Disease: Switch (to a Second Anti-TNF Agent) or Swap (for Another Mechanism of Action)?