Management of mucocutaneous and joint involvement of Behçet’s syndrome: a systematic literature review informing the 2025 update of the EULAR recommendations

Objectives: We aimed to update the evidence for the management of mucocutaneous and joint involvement of Behçet's syndrome (BS) to inform the 2025 update of European Alliance of Associations for Rheumatology (EULAR) recommendations. Methods: A systematic literature review was conducted to evaluate the benefits and harms of therapeutic interventions in patients with BS. All comparative studies were included, and in the absence of controlled studies for a specific intervention, noncomparative studies were also considered. We presented here the summary of the outcomes for mucocutaneous and joint involvement, overall disease activity and health-related quality of life (HRQoL). Results: Among the 7128 articles, 16 studies (7 randomised controlled trials [RCTs]) reported on mucocutaneous involvement, joint involvement, overall disease activity, or HRQoL. Apremilast was superior to placebo for oral ulcers in an RCT with low risk of bias (RoB). Few patients experienced genital ulcers, skin lesions, or arthritis during the 12 weeks. In the first head-to-head RCT with low RoB comparing adalimumab with infliximab, both drugs provided similar response rates for mucocutaneous manifestations, with a more rapid response observed with adalimumab. In other head-to-head RCTs, all with low RoB except for 1 with some concerns, the efficacy of immunosuppressive agents was confounded by concomitant glucocorticoid use for major organ involvement and by the small number of patients with active mucocutaneous manifestations. Conclusions: This systematic review supported the use of apremilast and tumour necrosis factor alpha inhibitors in patients with refractory mucocutaneous involvement and provided evidence for updating the 2025 EULAR Recommendations for the management of mucocutaneous and joint involvement of BS.