Management of major organ involvement in Behçet syndrome: a systematic literature review informing the 2025 update of the EULAR recommendations

Objectives: The objective of this study was to evaluate and update the evidence on pharmacologic and interventional treatments for major organ involvement in Behçet syndrome (BS), in order to inform the 2025 update of the European Alliance of Associations for Rheumatology recommendations. Methods: A systematic literature review was conducted using 2 distinct search strategies for pharmacologic and surgical/interventional therapies, covering major databases from October 2015 to November 2024. Controlled studies comparing active interventions with placebo or another active treatment were included. If no controlled trials were available for a specific research question, uncontrolled studies or case series with at least 10 patients with BS were included. Results: Of 7128 citations, 69 studies on major organ involvement and tapering/withdrawal of immunosuppressives were included. Only 5 were randomised controlled trials (RCTs), 4 of them included patients with eye involvement, and 1 included patients with vascular or nervous system involvement. RCTs and comparative observational studies for eye involvement supported the use of monoclonal tumour necrosis factor alfa inhibitors and interferon alfa. The RCT that included patients with vascular or nervous system involvement favoured infliximab over cyclophosphamide based on complete response rates and safety. Observational data additionally supported the use of interferon alfa for venous thrombosis, whereas the role of adjunctive anticoagulation remains unclear. Noncomparative observational studies showed benefit with monoclonal tumour necrosis factor alfa inhibitors in patients with gastrointestinal involvement. Conclusions: This systematic literature review provided evidence on the management of major organ involvement to inform the task force for developing the 2025 update of the European Alliance of Associations for Rheumatology recommendations for the management of BS.