Gizem Sevik, G. Lopalco, F. Iannone, M. Frassi, Matteo Piga, Giacomo Emmi, Piero Ruscitti, Francesco Ciccia, Ombretta Viapiana, Abdurrahman Tufan, Roberto Giacomelli, Antonella Insalaco, Ibrahim Almaghlouth, Francesco Carubbi, Andrés González-García, Alessandro Conforti, Rosaria Talarico, Gaafar Ragab, Stefano Gentileschi, Valeria Caggiano, J. Sota, C. Fabiani, Antonio Vitale, Luca Cantarini, Haner Direskeneli, Fatma Alıbaz-Öner
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 AutoInflammatory Disease Alliance (AIDA) Network Registry for BD. Patients who received any biologic 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 the 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 in the sample population for this study. Anakinra was the most frequently used agent (n = 31), with 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 in some patients previously unresponsive to anakinra. Tocilizumab (n = 15) showed favourable outcomes in ocular and neurological involvement (a 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 SpA. Ustekinumab (n = 3) and rituximab (n = 5) also demonstrated clinical improvement in selected refractory cases. No new major safety concerns were reported across the treatment groups. CONCLUSION: Biologics targeting IL-1, IL-6, IL-17 and the IL-12/23 pathways may offer therapeutic alternatives in BD patients unresponsive to TNF-α inhibitors. The treatment efficacy varied across phenotypes, highlighting the need for individualized treatment decisions.