The use of non-TNF targeted biologics in Behçet’s Disease: Real-life data from the International AIDA Network Behçet’s Disease Registry

Abstract Objectives Refractory manifestations of Behçet’s disease (BD) are commonly treated with TNF-α inhibitors; however, a subset of patients do not respond or are intolerant, prompting the need for alternative therapies. This study aimed to assess the real-life use, efficacy, and safety of non-TNF targeted biologic agents in BD. Methods Data were retrieved from the International AIDA Network Registry for BD. Patients who received any biological agent other than TNF-α inhibitors at any point during follow-up were included in the study. Clinical and demographic characteristics, prior treatments, and treatment responses at 3-, 6-, and 12-month follow-ups were collected. Results In total, 65 patients (36 female/29 male) with a mean age of 45.8 ± 13.3 years were included. Anakinra was the most frequently used agent (n = 31), 34.7% of patients with mucocutaneous, 73.3% with musculoskeletal, and 77.7% with ocular involvement showing a partial or complete response. Canakinumab (n = 11) was effective in mucocutaneous, musculoskeletal, and ocular involvement, including some previously unresponsive to anakinra. Tocilizumab (n = 15) showed favorable outcomes in ocular and neurological involvement (complete response in 5 of 6 patients), while 40% experienced worsening or no response in mucocutaneous manifestations. Secukinumab and ixekizumab were effective in patients with mucocutaneous-articular phenotypes, especially those with axial spondyloarthritis. Ustekinumab (n = 3) and rituximab (n = 5) also demonstrated clinical improvement in selected refractory cases. No new major safety concerns were reported across treatment groups. Conclusion Biologics targeting IL-1, IL-6, IL-17, and IL-12/23 pathways may offer therapeutic alternatives in BD patients unresponsive to TNF-α inhibitors. The treatment efficacy varies across phenotypes, highlighting the need for individualized treatment decisions.