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


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Crohn's & Colitis Centre and Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
P S A
PS
de Silva
D D
DD
Nguyen
J
J
Sauk
J
J
Korzenik
V
V
Yajnik
A N
AN
Ananthakrishnan
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha