title: Use of a third anti-TNF after failure of two previous anti-TNFs in patients with inflammatory bowel disease: is it worth it?
abstract: BACKGROUND
  Some patients with inflammatory bowel disease (IBD) never respond or lose their response to a second anti-TNF.
  
  
  OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Gastroenterology Unit, Hospital Universitario de La Princesa and Instituto de Investigación Sanitaria Princesa (IP) , Madrid , Spain.
authors: Javier P
authors: JP
authors: Gisbert
authors: María
authors: M
authors: Chaparro
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D000068582:Certolizumab Pegol / Q000627:therapeutic use; D057915:Drug Substitution; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D000069285:Infliximab / Q000627:therapeutic use; D019233:Retreatment; D017211:Treatment Failure; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068582:Certolizumab Pegol
keywords: Crohn’s disease; anti-TNF; failure; inflammatory bowel disease; intolerance; switch; ulcerative colitis