Novel therapies for Crohn's disease: focus on immunomodulators and antibiotics.

OBJECTIVE

To review the literature on novel immunomodulators such as tumor necrosis factor alpha (TNF-alpha)- and interleukin (IL)-related agents, 6-thioguanine (6-TG), tacrolimus, and leflunomide, and antibiotics such as ornidazole, rifaximin, and ciprofloxacin for the treatment of Crohn's disease.

DATA SOURCES: Literature was accessed through MEDLINE (1966-January 2006) using the terms Crohn's disease, novel therapies, immunomodulators, and antibiotics. Article references were hand-searched for additional relevant articles and abstracts.

STUDY SELECTION AND DATA EXTRACTION: All articles in English identified from the data sources were evaluated. Studies including greater than 5 patients with primarily adult populations were included in the review.

DATA SYNTHESIS: There are a number of new TNF-alpha and IL-related agents that may be useful for management of Crohn's disease. They include CDP 571, CDP 870, etanercept, onercept, thalidomide, IL-10, and IL-11. Several studies have shown that CDP 571 decreases the Crohn's Disease Activity Index score and is promising, especially in patients with refractory disease. 6-TG, tacrolimus, and leflunomide are among other immunomodulators that appear to have a role in refractory/severe disease. Finally, ornidazole, rifaximin, and ciprofloxacin are antimicrobials that may be used in patients who have failed other therapies or as adjunctive therapies.

CONCLUSIONS

A number of new treatment modalities are being investigated for Crohn's disease. Many of them are promising, and some of these agents may be considered in treatment-refractory patients in the future. However, some of the agents reviewed here are not available in the US. Future studies need to be double-blinded and placebo- or other treatment-controlled in a more homogeneous patient population.