Background The first EULAR recommendation for the management of Behçet's syndrome (BS) was published in 2008 and since then new data including biologic agents have appeared.
Objectives To review the evidence for efficacy and safety of management strategies in BS patients with eye, vascular, gastrointestinal (GI) and neurologic involvement.
Methods We used the GRADE methodology as framework for guidelines development. For the systematic literature review, we searched The Cochrane Library, Database of Abstracts of Reviews of Effects, Health Technology Assessments, MEDLINE, EMBASE and International Pharmaceutical Abstracts Database. Randomized controlled trials (RCT), controlled clinical trials, or open label trials comparing an active drug in patients with BS with other agents or placebo were included. If controlled trials were not available for answering a specific research question, uncontrolled evidence from prospective or retrospective studies or case series about a minimum of 5 patients were also included.
Results We reviewed the titles and abstracts of 3927 references, followed by the full texts of 397. A total of 166 studies related with major organ involvement met our inclusion criteria. Three RCTs with cyclosporine-A (CycA) and 1 with azathioprine (AZA) showed beneficial results in BS patients with eye involvement. There were several observational studies with interferon-α and TNF-α antagonists in patients with eye involvement, including those among patients refractory to conventional treatment modalities. Decreases in the frequency of ocular attacks, remission and improvement in visual acuity were observed in the majority of patients treated with these agents. As for vascular involvement, retrospective studies showed that immunosuppressives (IS) significantly decreased the frequency of recurrences in BS patients with deep vein thrombosis (RR 95%CI: 5.8, 2.8–11.8). A similar effect was not observed with anticoagulants+IS compared with IS alone (RR 95%CI: 1.5, 0.8–2.6). Observational studies showed that cyclophosphamide and high dose glucocorticoids (GC) decreased mortality in patients with arterial aneurysms. Treatment with IS and GC decreased postoperative complications in patients who had surgery for arterial aneurysms. Observational studies showed beneficial results with 5-ASA derivatives and AZA in the initial management of BS patients with GI involvement. Remission could be obtained with thalidomide and/or TNF- α antagonists in the majority of patients with refractory GI involvement. Retrospective studies also showed IS decreased postoperative recurrences in patients operated for intestinal perforations or major bleeding (RR 95%CI: 0.56, 0.33–0.95). Observational studies in BS patients with neurologic involvement showed IS and GC improved the outcome. CycA should be avoided in such patients since retrospective studies showed that CycA had increased the risk of development of neurologic involvement (RR 95%CI: 12.6, 4.7–33.7).
Conclusions It is sobering to note that the majority of the studies forming the basis for the recommendations related to major organ involvement in the updated EULAR recommendations for the management of BS come from observational studies.
Disclosure of Interest None declared