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)?

Abstract

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.

Real-World Evidence of the Effectiveness and Safety of Ustekinumab for the Treatment of Crohn’s Disease: Systematic Review and Meta-Analysis of Observational Studies

“…Inflammatory bowel disease (IBD) comprises a series of chronic disorders of unknown cause affecting the gastrointestinal tract, and it is associated with a complex immune response. Treatment options for IBD are rapidly expanding because the currently available treatments are still ineffective in many patients [ 1 , 2 , 3 , 4 ].…”

Sphingosine 1-Phosphate Modulation in Inflammatory Bowel Diseases: Keeping Lymphocytes Out of the Intestine

“…Still, several limitations of these therapies remain to be overcome: their potential immunogenicity, the parenteral administration and the high rates of loss of response/disease relapse. Particularly, around one-third to half of IBD patients initiating a biologic agent experience a primary non-response, and a further half of the patients develop a secondary loss of response [ 10 , 11 , 12 ]. Costs associated with biologics’ production and reimbursements have been further limiting the use of these agents [ 13 ].…”

Tofacitinib: A Small Molecule for Biologic-Refractory Crohn’s Disease?

“…At week 8, mean decreases from baseline C-reactive protein (CRP) concentration were significantly greater with tofacitinib 5 and 10 mg twice daily (p < 0.001) compared with placebo. Notably, > 70% of the trial population had been previously exposed to anti-TNF biologics, a factor that negatively impacts the subsequent efficacy of subsequent biologics and other anti-inflammatory drugs [4].…”