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Scand J Gastroenterol. 2015 Apr;50(4):379-86. doi: 10.3109/00365521.2014.928901. Epub 2015 Jan 30.

Use of a third anti-TNF after failure of two previous anti-TNFs in patients with inflammatory bowel disease: is it worth it?

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Gastroenterology Unit, Hospital Universitario de La Princesa and Instituto de Investigación Sanitaria Princesa (IP) , Madrid , Spain.



Some patients with inflammatory bowel disease (IBD) never respond or lose their response to a second anti-TNF.


To review the efficacy and safety of a third anti-TNF after failure of two previous anti-TNFs. Methods. Bibliographical searches in PubMed for studies evaluating infliximab, adalimumab, or certolizumab as the third anti-TNF in IBD patients whose two previous anti-TNF treatments had failed.


Two retrospective studies with a small sample size and limited follow up evaluated the effectiveness of a third anti-TNF patients whose two previous anti-TNFs had failed. The arguments for this switching strategy are as follows: a)favorable--albeit limited--efficacy (in the study by Allez et al., clinical response was observed in 51% of patients at week 20; and in the study by de Silva et al., over 50% of patients remained on the third anti-TNF at 1 year); b)the eventual response to the third anti-TNF is relatively quick; c) no other medical options have been approved for IBD treatment; d)the only alternative options are surgery, compassionate use with non-anti-TNFs, and clinical trials. However, there are also arguments against the prescription of a third anti-TNF: a)lack of experience, since the few available studies are limited by their small sample size; b)the relatively low response in the long term (mainly due to loss of response); c) and finally, and most importantly, the risk of severe adverse events.


The delicate balance between pros and cons means the use of a third anti-TNF after failure of two previous agents should be considered only in patients with no other therapeutic options. Decisions should be taken on an individual basis.


Crohn’s disease; anti-TNF; failure; inflammatory bowel disease; intolerance; switch; ulcerative colitis

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