TNF-alpha gene expression in colorectal mucosa as a predictor of remission after induction therapy with infliximab in ulcerative colitis

Cytokine. 2009 May;46(2):222-7. doi: 10.1016/j.cyto.2009.02.001. Epub 2009 Mar 14.

Abstract

Background: It has been documented that treatment with infliximab (IFX) induces remission in 1/3 of patients with moderate to severe ulcerative colitis (UC). Predictors of response could improve selection of patients with a higher probability of favorable outcome.

Aim: To determine predictor factors for the clinical outcome of IFX induction therapy in UC.

Methods: UC patients with moderate to severe disease who received 5mg/kg IFX at weeks 0, 2 and 6weeks were included. Ulcerative colitis disease activity index (UCDAI) score including endoscopic sub-scores were assessed before and after treatment. Several predictors, including TNF-alpha mRNA expression, were tested in a regression model.

Results: Fifty-nine patients completed the study. Age, gender, steroid therapy, immunosuppressive, pancolitis, endoscopic sub-score, disease duration, C-reactive protein, interleukin-(IL)-4, IL-10 or interferon-gamma (IFN-gamma) did not predict mucosal or clinical remission. There was an inverse and independent association between pre-treatment TNF-alpha expression levels and clinical and endoscopic remission of IFX treatment (logistic regression, p=0.01 and p=0.003, odds ratio 2.5 and 4.8, respectively).

Conclusion: The clinical outcome of an induction therapy with IFX in UC is inversely associated with the pre-treatment gene expression levels of TNF-alpha in colorectal mucosa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-Inflammatory Agents / therapeutic use*
  • Antibodies, Monoclonal / therapeutic use*
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / genetics*
  • Colitis, Ulcerative / pathology
  • Colitis, Ulcerative / physiopathology
  • Colon / anatomy & histology
  • Female
  • Gene Expression Regulation*
  • Humans
  • Infliximab
  • Intestinal Mucosa / physiology*
  • Male
  • Middle Aged
  • Prospective Studies
  • Rectum / anatomy & histology
  • Remission Induction
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha* / genetics
  • Tumor Necrosis Factor-alpha* / metabolism
  • Young Adult

Substances

  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal
  • Tumor Necrosis Factor-alpha
  • Infliximab