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

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

Abstract

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.

Aim: 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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal / therapeutic use*
  • Female
  • Humans
  • Inflammatory Bowel Diseases / drug therapy*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Tumor Necrosis Factor-alpha