OBJECTIVE: Off-label use of anti-tumor necrosis factor (TNF) agents for Behçet's disease (BD) is increasing. We evaluated published data on their efficacy and safety for patients with unmet medical needs due to severe disease manifestations, including ocular, gastrointestinal, and central nervous system involvement. METHODS: Peer-reviewed articles on anti-TNF agents for BD appearing in Medline/PubMed through March 2010 were identified using the appropriate indexing terms. RESULTS: We found 88, 12, and 13 primary articles from 20 countries on infliximab, etanercept, and adalimumab, reporting on 325, 37, and 28 patients, respectively. All patients were inadequately controlled with, or intolerant to, other immunosuppressive regimens, including interferon; 20 patients received more than 1 anti-TNF agent. In the only randomized placebo-controlled trial, 4-week administration of etanercept was effective in suppressing most of the mucocutaneous manifestations. In 16 open prospective studies evaluating the effect of repetitive infliximab injections (174 patients in total, men:women = 3:1, median follow-up = 16.2 months), sustained organ-specific, clinical responses were evident in 90%, 89%, 100%, and 91% of patients with resistant mucocutaneous, ocular, gastrointestinal, and central nervous system involvement, respectively. Combination of infliximab with azathioprine and/or cyclosporine-A appeared superior to monotherapy for sustained ocular remission. However, due to the fact that necessary data were lacking, formal estimation of anti-TNF treatment effect on the disease activity indexes for different organ involvement was not possible. CONCLUSIONS: Although more controlled data are needed, there is enough published experience to suggest that TNF blockade represents an important therapeutic advancement for patients with severe and resistant, or intolerant, to standard immunosuppressive regimens BD.
OBJECTIVE: Off-label use of anti-tumor necrosis factor (TNF) agents for Behçet's disease (BD) is increasing. We evaluated published data on their efficacy and safety for patients with unmet medical needs due to severe disease manifestations, including ocular, gastrointestinal, and central nervous system involvement. METHODS: Peer-reviewed articles on anti-TNF agents for BD appearing in Medline/PubMed through March 2010 were identified using the appropriate indexing terms. RESULTS: We found 88, 12, and 13 primary articles from 20 countries on infliximab, etanercept, and adalimumab, reporting on 325, 37, and 28 patients, respectively. All patients were inadequately controlled with, or intolerant to, other immunosuppressive regimens, including interferon; 20 patients received more than 1 anti-TNF agent. In the only randomized placebo-controlled trial, 4-week administration of etanercept was effective in suppressing most of the mucocutaneous manifestations. In 16 open prospective studies evaluating the effect of repetitive infliximab injections (174 patients in total, men:women = 3:1, median follow-up = 16.2 months), sustained organ-specific, clinical responses were evident in 90%, 89%, 100%, and 91% of patients with resistant mucocutaneous, ocular, gastrointestinal, and central nervous system involvement, respectively. Combination of infliximab with azathioprine and/or cyclosporine-A appeared superior to monotherapy for sustained ocular remission. However, due to the fact that necessary data were lacking, formal estimation of anti-TNF treatment effect on the disease activity indexes for different organ involvement was not possible. CONCLUSIONS: Although more controlled data are needed, there is enough published experience to suggest that TNF blockade represents an important therapeutic advancement for patients with severe and resistant, or intolerant, to standard immunosuppressive regimens BD.