Although corticosteroids are effective for treating Crohn's disease, approximately 20% of patients who respond become sick again when steroids are withdrawn and become steroid dependent. Furthermore, corticosteroids exhibit significant adverse effects. TNF alpha is a chemical that causes some of the inflammation of Crohn's disease. Tumor necrosis factor (TNF) alpha blocking drugs may provide an alternate treatment for patients who do not respond to corticosteroid or immunosuppressive drug treatment. This review shows that a single intravenous infusion of infliximab (5 mg/kg) may be an effective treatment for patients with active Crohn's disease who no longer respond to corticosteroids or immunosuppressive drugs. There is also some evidence that CDP571, another TNF alpha blocking drug may be effective. There is no evidence to support the use of etanercept, a drug that blocks the action of TNF alpha by binding to receptors. There were no serious side effects associated with TNF blocking drugs, although the follow-up period of the studies reported in this review may have been too short to assess the development of serious side effects.
Evidence from one randomized controlled trial suggests that a single infusion of infliximab may be effective for induction of remission in Crohn's disease. Based on this study, we can recommend a dose of 5 mg/kg. There is also some evidence that CDP571 may be effective in inducing remission in Crohn's disease. We did not find any evidence that supports the use of etanercept in Crohn's disease. The period of follow up for the patients in these studies was probably too short to allow adequate assessment of recently reported serious adverse effects such as tuberculosis and lymphoma.
Crohn's disease may be refractory to conventional treatments such as corticosteroids, enteral nutrition and immuno-suppressive agents. A number of patients with the disease may also become steroid-dependent leading to increased risk of developing steroid-related adverse effects. Recent studies suggest that TNF-a blocking agents may be effective in inducing remission in Crohn's disease.
To conduct a systematic review to evaluate the effectiveness of TNF-a blocking agents in inducing remission in patients with active Crohn's disease.
We searched MEDLINE (1966-June 2003), EMBASE (1984-June 2003), the Cochrane Central Register of Controlled Trials from the Cochrane Library (Issue 2, 2003) and the IBD Review Group Specialized Trials Register. We hand-searched the articles cited in each publication obtained.
We included only randomised controlled trials in which patients with active Crohn's disease (defined by a validated Crohn's disease activity index) were randomly allocated to receive a TNF-a blocking agent in the treatment arm , or to receive placebo or another treatment in the comparison arm.
Data extraction and assessment of the methodological quality of each trial were independently performed by two reviewers. Any disagreement among reviewers was resolved by consensus. Outcome measures reported in the primary studies included clinical remission, clinical response and changes in disease activity index.
Ten studies were identified of which 4 met the inclusion criteria. The included studies either differed in the type of TNF-a blocking agent used or in the way outcomes were assessed to such an extent that we considered it inappropriate to combine the data statistically. There is evidence from one randomised controlled trial that suggests that a single intravenous infusion of the monoclonal antibody cA2, infliximab, may be effective for induction of remission in Crohn's disease. There was no difference in response rates among infliximab doses of 5, 10 or 20 mg/kg. The results of two other trials suggested that CDP571, the genetically engineered human TNF monoclonal antibody, may also be effective in reducing disease activity index at 2 weeks after an infusion. We did not find any evidence to support the use of etanercept in Crohn's disease.