Risk of intestinal involvement in mucocutaneous-onset Behçet’s disease: data from the AIDA network registry Antonio Vitale, Valeria Caggiano, Jessica Sbalchiero, Francesco Gavioli, Giuseppe Lopalco, et al. Frontiers in Immunology, 2026 Objective Behçet’s disease (BD) may initially manifest solely with mucocutaneous involvement. This study aimed to identify demographic and clinical factors associated with subsequent intestinal involvement in patients presenting exclusively with mucocutaneous manifestations during early disease stages. Methods Data were obtained from the International AutoInflammatory Disease Alliance Network registry dedicated to BD; a Bayesian statistical approach was employed to address the limited sample size resulting from subgroup stratifications. Results In total, 328 BD patients with exclusively mucocutaneous onset were enrolled; of these, 46 (14%) developed intestinal involvement over time. The risk of ocular involvement was higher among patients with intestinal manifestations (OR: 3.02, 95% CrI: 1.24–6.08; posterior probability: 99.3%). Minor aphthous ulcers without major aphthosis were protective towards intestinal involvement (OR: 0.47, 95% CrI: 0.22–0.98; posterior probability: 97.98%). Conversely, major aphthous ulcers increased the risk (OR: 3.25, 95% CrI: 1.50–7.02; posterior probability: 99.7%), along with the combination of oral major aphthosis with: i) genital aphthosis (OR = 2.77, 95%CrI: 1.14-6.58; posterior probability: 98.45%); ii) pseudofolliculitis (OR = 3.18, 95%CrI: 1.15-8.33; posterior probability: 98.72%); iii) genital aphthosis plus pseudofolliculitis (OR = 5.22, 95%CrI: 1.71-16.35; posterior probability of 99.77%). Pseudofolliculitis plus cutaneous manifestations other than erythema nodosum were protective against intestinal involvement (OR = 0.01, 95%CrI: 0.0-0.98; posterior probability: 97.55%). Conclusion Major aphthosis was the strongest factor associated with intestinal involvement in BD patients initially presenting with mucocutaneous symptoms only. In such patients, intestinal involvement correlated with increased risk of ocular inflammation.
Application of machine learning techniques to explore the occurrence of macrophage activation syndrome in Still’s disease: results from the GIRRCS AOSD Study Group and the AIDA Network Still’s Disease Registry Piero Ruscitti, Francesco Masedu, Antonio Vitale, Valeria Caggiano, Ilenia Di Cola, et al. Frontiers in Immunology, 2026 Objectives This study aims to explore the application of machine learning techniques in assessing macrophage activation syndrome (MAS) in Still’s disease. Methods A multicenter, observational, prospective study was conducted, including patients with Still’s disease enrolled in the Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) AOSD Study Group and the AutoInflammatory Disease Alliance (AIDA) Network Still’s Disease Registry. Results A total of 737 patients (age: 35.5 ± 17.8, male sex: 44.7%) with Still’s disease were assessed; 11.4% were affected by MAS, and 3% had a poor prognosis. First, random forest imputation was applied to the original dataset. Subsequently, a machine-learning-driven assessment was developed to explore MAS occurrence. Collectively, regression models, an exploration decision tree, and a random forest were applied, suggesting the importance of ferritin, age, C-reactive protein (CRP), and systemic score. A logistic regression model accounting for data leakage concerns was then generated using these variables, and missing values were imputed using random forest imputation. This analysis supported the role of the selected variables, which were further combined across different clinical scenarios to estimate the probability of MAS. The highest risk of MAS was estimated for patients simultaneously characterized by age ≥ 45 years, ferritin ≥ 4,178.10 ng/mL, CRP ≥ 27.15 mg/L, and a systemic score ≥ 7, corresponding to a 34.7% probability of MAS, as well as for those characterized by ferritin ≥ 4,178.10 ng/mL, CRP ≥ 27.15 mg/L, and systemic score ≥ 7, corresponding to a 33.5% probability of MAS. Conclusions A machine-learning-driven prediction of MAS was explored in Still’s disease, highlighting the importance of age of onset, hyperferritinaemia, increased CRP, and multiorgan involvement. A combination of these features may suggest a clinician-friendly algorithm for stratifying the probability of MAS during Still’s disease.
Depemokimab and the twice-yearly regimen: pharmacological implications and therapeutic positioning in severe eosinophilic respiratory diseases A. M. Marra, E. Bizzi, A. Gidaro, F. Bini, S. Rotunno, et al. Frontiers in Immunology, 2026 Type 2 inflammatory diseases (T2D), notably severe eosinophilic asthma (SEA) and chronic rhinosinusitis with nasal polyps (CRSwNP), represent a significant global health burden due to their high morbidity, frequent exacerbations and reliance on systemic glucocorticoids (SGCs). Targeting Interleukin-5 (IL-5), a key driver of eosinophil production and survival, has emerged as a validated therapeutic strategy. Depemokimab is a novel, first-in-class anti-IL-5 monoclonal antibody (mAb) engineered with an extended half-life via the YTE amino acid modification of its Fc region, enabling an unprecedented twice-yearly dosing interval. This review synthesizes clinical data from the Phase III SWIFT (SEA) and ANCHOR (CRSwNP) programs, demonstrating depemokimab’s sustained eosinophil depletion and significant reduction in asthma exacerbation rates (annualized asthma exacerbation rate reduction of approximately 54% versus placebo). While efficacy on secondary endpoints such as lung function (FEV1) and quality of life (QoL) was mixed, the efficacy in reducing nasal polyp size (Nasal Polyp Score and Nasal Congestion) in CRSwNP was clear. The core value proposition of depemokimab is the combination of established IL-5 inhibition efficacy with patient convenience due to its dosing. We discuss its pharmacodynamic profile, safety and pivotal role in shifting the treatment paradigm towards simplified chronic disease management, positioning depemokimab as a novel, patient-centric option in the competitive landscape of T2 biologic therapies.
Risk of major organ involvement in Behçet's patients with mucocutaneous onset: Data from the AIDA Network Registry Antonio Vitale, Francesco Gavioli, Valeria Caggiano, Jessica Sbalchiero, Giuseppe Lopalco, et al. Rheumatology, 2026 Objectives The progression of Behçet’s disease (BD) from a mucocutaneous-limited form to major organ involvement (MOI) represents a significant challenge. This study aims to identify patients without MOI at BD onset who are at increased risk of developing MOI in later stages. Methods Patients’ data were drawn from the International AutoInflammatory Disease Alliance (AIDA) Network registry dedicated to BD. Results A total of 328 patients with exclusively mucocutaneous manifestations at BD onset were enrolled. Of these, 82 patients (25%) developed MOI over the entire follow-up period. Patients with minor oral aphthosis and no major oral aphthosis exhibited a reduced risk of developing MOI, with an odds ratio (OR) of 0.41 [95% confidence interval (95%CI): 0.22–0.79, P = 0.008]. Conversely, patients with both major and minor oral aphthosis had a significantly higher risk of developing MOI, with an OR of 12.76 (95%CI: 1.44–113, P = 0.02). Moreover, the development of MOI was associated with major oral aphthosis plus genital aphthosis (OR: 2.49, 95%CI: 1.1–5.6, P = 0.03), major oral aphthosis plus pseudofolliculitis (OR: 2.9, 95%CI: 1.15–7.4, P = 0.02) and major oral aphthosis plus both genital aphthosis and pseudofolliculitis (OR: 3.73, 95%CI: 1.22–11.4, P = 0.02). A positive family history for BD was associated with MOI (OR: 2.85, 95%CI: 1.08–7.58, P = 0.03). Conclusion A positive family history and the presence of major oral aphthosis combined with minor oral aphthosis, genital aphthosis or pseudofolliculitis are associated with MOI development in patients with mucocutaneous BD at onset.
