Anti-TNF therapy in the management of Behcet's disease--review and basis for recommendations.

Summary and conclusions The published evidence on the use of anti-TNF agents in BDconsists mainly of reports of the open use of infliximab,principally evaluated as an add-on therapy. The majority ofpatients suffered from relapsing, posterior segment ocularinflammation, inadequately controlled with available immuno-suppressive therapy. With infliximab, a fast-onset therapeuticeffect was repeatedly observed in patients with sight-threateninginflammation, including patients with retinal vasculitis. Thepaucity of effective and fast-acting therapies particularly forpatients with eye disease underscores the importance of thesefindings. As suggested by three independent, open-label, prospec-tive, self-controlled studies, repetitive infliximab infusions werealso effective in preventing ocular relapses, maintaining visualacuity and tapering immunosuppressive therapy in the majority ofpatients who had an inadequate response or were intolerant toconventional therapy. Infliximab was effective for extra-ocularmanifestations in these patients, as well as in other patients withrecalcitrant orogenital ulcers, arthritis, intestinal or centralnervous system involvement and in a single patient withpulmonary artery aneurysm. With short-term use, there were noserious side effects reported. The only randomized controlled trialwas a 4-week study of etanercept in patients with mucocutaneousmanifestations. Etanercept was beneficial for most of thesemanifestations, but no data are at hand from this study on eyeinvolvement.Anti-TNF agents have a number of disadvantages, includinginduction of potentially serious adverse events and high cost.However, based on the available evidence, physicians may decideto provide anti-TNF therapy to patients with definite BD.However, until results from adequately powered, randomizedcontrolled clinical trials are available, TNF blocking agentsshould be used with caution only for selected patients withsevere disease. Patients with two or more relapses of posterioruveitis per year, low visual acuity due to chronic cystoid macularoedema, or active CNS disease and/or selected patients withintestinal inflammation, or arthritic and mucocutaneous manifes-tations that reduce significantly the quality of life, would fit thiscategory. According to the experience accumulated so far,infliximab seems to be more efficacious than etanercept in diseasemanifestations other than mucocutaneous or joint involvement,while data on adalimumab are very limited. Infliximab oretanercept is recommended as an add-on therapy for selectedpatients with BD, who are refractory or intolerant to traditionalimmunosuppressive regimens. Moreover, a single infusion ofinfliximab (5mg/kg), can be used as a first-line agent for sight-threatening, bilateral posterior eye segment inflammation, whenthe fast-onset of response is considered to be critical to preventfixed retinal lesions and thus permanent visual loss. In those caseswhose ocular relapses are not controlled by azathioprine and/orciclosporin, a maintenance therapy with infliximab at the dose of5mg/kg every 6–8 weeks could be used for up to 2 years, providedno relapses occur between intervals. These recommendations donot constitute treatment guidelines but are intended to improvepractice uniformity and to help physicians in the management ofBD patients, until higher grades of evidence are available.