Efficacy and safety of tumor necrosis factor antagonists in Crohn's disease: meta-analysis of placebo-controlled trials.

BACKGROUND & AIMS: We performed a meta-analysis of placebo-controlled trials to evaluate safety and efficacy of tumor necrosis factor (TNF) antagonists for Crohn's disease.

METHODS

We searched MEDLINE, Cochrane Library, and EMBASE. The primary end points were clinical remission for luminal Crohn's disease and fistula closure at > or =2 consecutive visits. Deaths, serious infections, and malignancies were also analyzed by the methods of Peto and Der Simonian and Laird.

RESULTS

Fourteen luminal Crohn's disease trials enrolled 3995 patients. In overall analysis, anti-TNF therapy was effective for induction of remission at week 4 (mean difference, 11%; 95% confidence interval [CI], 6%-16%; P < .001) and maintenance of remission at weeks 20-30 in patients who responded to induction therapy and in patients randomized before induction (mean difference, 23%; 95% CI, 18%-28% and mean difference, 8%; 95% CI, 3%-12%, respectively; P < .001 for all comparisons). Ten studies evaluated anti-TNF for treatment of fistulizing Crohn's disease, involving 776 patients. In overall analysis, anti-TNF therapy was effective for fistula closure only in maintenance trials after open-label induction (mean difference, 16%; 95% CI, 8%-25%; P < .001). In 21 studies enrolling 5356 individuals, anti-TNF therapy did not increase the risk of death, malignancy, or serious infection.

CONCLUSIONS

Infliximab, adalimumab, and certolizumab are effective in luminal Crohn's disease. Efficacy of anti-TNF agents other than infliximab in treating fistulizing Crohn's disease requires additional investigations. A longer duration of follow-up and a larger number of patients are required to better assess the safety profile of TNF antagonists in Crohn's disease.