Behcet's disease
Anti-TNF Agents for Behçet's Disease: Analysis of Published Data on 369 Patients

https://doi.org/10.1016/j.semarthrit.2010.09.002Get rights and content

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.

Section snippets

Methods

We conducted an extensive Medline/PubMed search for primary articles published in any language through March 2010 reporting on the therapeutic use of anti-TNF agents in BD using the guidelines of the PRISMA Statement for presentation of systematic reviews (Fig. 1). Search terms included “anti-TNF agents,” “infliximab,” “etanercept,” “adalimumab,” “certolizumab pegol,” and “golimumab,” each in combination with “Behcet's disease,” as well as with distinct BD manifestations, such as “uveitis,”

Results

We found 88 articles on the use of infliximab, 12 articles on etanercept, and 13 articles on adalimumab, reporting on 325, 37, and 28 patients, respectively. Nineteen of a total of 369 patients were treated with 2 different anti-TNF agents, whereas 1 additional patient received all 3. No articles on the use of certolizumab pegol or golimumab had been published up to March 2010. As shown in Table 1, the majority of these articles consisted of case reports (a reference list of case reports is

Discussion

To date, the published experience on the off-label use of anti-TNF agents in patients with BD is coming from 20 different countries. We analyzed the current evidence deriving from 369 patients who were refractory to conventional therapies. There was significantly more information on the therapeutic effect of infliximab compared with etanercept and adalimumab, since 83% of patients received infliximab. We found that therapeutic TNF blockade was efficacious in more than 85% of patients with

Acknowledgment

This work was supported by Athens University Medical School (ELKE Grant 967).

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