The European Alliance of Associations for Rheumatology has updated its recommendations for the management of Behçet’s syndrome, with revised guidance across five overarching principles and 12 recommendations organized by organ involvement. The update places greater emphasis on earlier biologic use in patients with eye, vascular, and nervous system involvement, while maintaining a step-up approach for mucocutaneous and joint disease.

The recommendations update the 2018 version and were developed by a 29-member task force from 11 countries. The group reviewed 81 studies, including nine randomized controlled trials, 34 comparative observational studies, and 38 noncomparative observational studies. The final document includes one new recommendation, seven modified recommendations, and four recommendations with wording changes only.

“However, due to the importance of rapid and effective suppression of inflammation to prevent organ damage and based on studies showing their superiority to csDMARDs, earlier use of bDMARDs is recommended in patients with eye, vascular, and nervous system involvement,” wrote lead researcher Gulen Hatemi of Istanbul University-Cerrahpasa Medical School in Türkiye, and colleagues.

The overarching principles stress the relapsing and remitting nature of Behçet’s syndrome, the need to prevent irreversible organ damage and maximize health-related quality of life, ongoing assessment for organ involvement, individualized treatment, and multidisciplinary care with patient education and shared decision-making.

For mucocutaneous involvement, colchicine remains the first-line treatment for recurrent lesions. In patients whose disease is refractory to or who cannot tolerate colchicine, apremilast or tumor necrosis factor alpha inhibitors should be considered. The recommendations also state that topical glucocorticoids can be used for oral and genital ulcers, while chronic use of systemic glucocorticoids should be avoided.

The paper cites randomized trial data supporting colchicine as first-line therapy and notes newer evidence for escalation options. In a small randomized trial, mucocutaneous remission at 6 months was 100% with adalimumab and 86% with infliximab, with a shorter median time to response with adalimumab. A retrospective study suggested similar response rates between apremilast and tumor necrosis factor alpha inhibitors for oral and genital ulcers.

For joint involvement, the task force did not make major changes. Colchicine remains the first-line treatment for acute arthritis, and immunosuppressives should be considered in recurrent or chronic disease.

For Behçet’s uveitis, the recommendations state that immunosuppressive treatment should be given in all patients, with the goal of inducing and maintaining clinical and angiographic remission. In patients with sight-threatening posterior-segment inflammation, monoclonal anti–tumor necrosis factor alpha antibodies should be used, preferably infliximab in combination with other immunosuppressives. Glucocorticoids should not be used as monotherapy.

The update cites randomized data showing that adalimumab was superior to cyclosporine-A for controlling uveitis, with a lower annual relapse rate, while annual relapse rates were similar between adalimumab and interferon-alpha. Another small randomized study found similar visual acuity outcomes with infliximab and interferon-alpha.

In arterial involvement, the task force now recommends high-dose glucocorticoids plus infliximab for pulmonary and peripheral artery aneurysms, with cyclophosphamide as an alternative. It also recommends maintenance immunosuppression, preferably with monoclonal anti–tumor necrosis factor alpha antibodies. The paper says this change reflects growing evidence and experience supporting infliximab over cyclophosphamide in this setting.

That shift was supported in part by a randomized trial comparing infliximab with cyclophosphamide in patients with severe Behçet’s syndrome involving vascular and nervous system disease. Although the study was small and included mixed forms of vascular involvement, infliximab was associated with higher remission rates at 24 weeks and fewer mild to moderate adverse events.

For venous thrombosis, the recommendations emphasize prompt treatment with glucocorticoids and immunosuppressives, with consideration of monoclonal anti–tumor necrosis factor alpha antibodies; anticoagulants may be added in selected cases with caution for bleeding risk.

For gastrointestinal involvement, the recommendations state that diagnosis, severity assessment, and management should be based on endoscopy. In patients with mild to moderate disease, 5-aminosalicylic acid or azathioprine may be used with or without glucocorticoids, while monoclonal anti–tumor necrosis factor alpha antibodies should be considered in severe or refractory disease.

For active parenchymal nervous system involvement, the task force recommends high-dose glucocorticoids and immunosuppressives, preferably infliximab, followed by slow glucocorticoid tapering and maintenance immunosuppression. The paper says the earlier practice of starting with azathioprine and reserving tumor necrosis factor alpha inhibitors for refractory disease has shifted toward first-line biologic use because of the risk for disability.

Agreement scores were high overall across the recommendations. In the summary table, mean levels of agreement ranged from 8.7 to 9.8, and most recommendations were scored 8 or higher by most task force members. Two quality indicators were identified from the recommendations with the highest implementation and quality-of-care impact scores: one for joint involvement and one for arterial involvement.

The researchers noted several limitations, including the small size of randomized trials, heterogeneity in trial populations and outcome measures, and reliance on observational data in several treatment domains. They also highlighted evidence gaps in treatment sequencing, tapering and discontinuation strategies, monitoring approaches, and management of refractory disease.

The paper includes disclosures for several researchers, including reported research support, speaker fees, and consulting fees from multiple pharmaceutical companies.

Source: Annals of the Rheumatic Diseases