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Aliment Pharmacol Ther. 2012 Sep;36(5):459-66. doi: 10.1111/j.1365-2036.2012.05214.x. Epub 2012 Jul 11.

Long-term outcome of a third anti-TNF monoclonal antibody after the failure of two prior anti-TNFs in inflammatory bowel disease.

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  • 1Crohn's & Colitis Centre and Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA 02114, USA.



A significant proportion of patients with IBD lose response to anti-TNF therapies. There is limited knowledge of the long-term outcomes of those who have failed two anti-TNF agents and commenced a third.


To examine the safety and efficacy of third anti-TNF treatment after failure of two prior anti-TNF agents in patients with inflammatory bowel disease.


This was a retrospective study of all IBD patients [Crohn's disease (CD), ulcerative colitis (UC)] treated with a third anti-TNF agent after loss of response or intolerance to two prior anti-TNF agents at a single tertiary North American centre. Disease activity, drug therapy and Montreal phenotypes were noted at disease onset and commencement of the third anti-TNF agent. Kaplan-Meier estimates were used to calculate the probability of remaining on the third anti-TNF agent and to identify predictors of long-term clinical response.


A total of 63 patients (64% women, 57 CD and 6 UC) were included in the analysis. The mean disease duration at initiation of third anti-TNF was 12 years. Thirty-five (55.6%) patients discontinued the third anti-TNF after a mean of 13.2 months. Probability of remaining on the third anti-TNF was 0.69, 0.55, 0.37 and 0.25 at 6, 12, 24 and 36 months respectively. Prior primary nonresponders to the first anti-TNF agent [hazard ratio (HR) 6.4, 95% CI 2.5-16.1] and persistent disease activity at 3 months after commencement of a third anti-TNF (HR 3.2, 95% CI 1.3-7.8) predicted poorer response.


Over half of patients with inflammatory bowel disease, initiated on a third anti-TNF agent after failure of two prior anti-TNF drugs, are able to remain on the third anti-TNF at 1 year.

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