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


OBJECTIVE
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).


CONCLUSIONS
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.
Olsen
Trine
T
Laboratory of Gastroenterology, Institute of Clinical Medicine, University of Tromsø, Breivika, N-9037 Tromsø, Norway.
Goll
Rasmus
R
Cui
Guanglin
G
Christiansen
Ingrid
I
Florholmen
Jon
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D003106:Colon / Q000033:anatomy & histology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D000069285:Infliximab; D007413:Intestinal Mucosa / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012007:Rectum / Q000033:anatomy & histology; D012074:Remission Induction; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab