Background: Following the results of the MANDARA trial, this real-life study aimed at comparing the effectiveness and safety profile of mepolizumab versus benralizumab in a European EGPA cohort. Methods: We conducted a retrospective observational comparative study including EGPA patients, who received mepolizumab or benralizumab at the asthma dose. Patients were matched 1:1 by sex, age, BVAS and oral corticosteroid (OCS) dosage at the treatment initiation (T0). Complete response (CR) and partial response (PR), disease activity, OCS, pulmonary parameters, eosinophil count, relapses, and safety outcomes were also compared at 3, 6 and 12 months. Results: Patients treated with mepolizumab or benralizumab (n=88 each) were matched: 57% were females, median age was 54 years (IQR 45-60), median OCS dose 10 (7.5-12.5) and 10 (7-13) mg/day, median BVAS 4 (2-7) and 3 (2-8), respectively. 45.4% of patients in the mepolizumab group and 51.1% in the benralizumab group achieved CR or PR at T3, with CR steadily increasing during follow-up for both treatments. At T12, a higher CR rate was found in the benralizumab group (48.1% vs 32.4%, p=0.005). No differences in BVAS, OCS, and respiratory parameters were observed between groups at the different timepoints. Throughout the follow-up, both treatments reduced eosinophil count, although a deeper reduction was found in the benralizumab group at all timepoints (p<0.0001). Safety profile was comparable between patient groups. Conclusion: Mepolizumab and benralizumab showed comparable overall effectiveness and safety in EGPA. However, benralizumab achieved a higher CR rate at T12, and a deeper peripheral eosinophil reduction.

Objective: Behçet’s syndrome (BS) is a systemic vasculitis with several clinical manifestations. Neutrophils hyperactivation mediates vascular BS involvement, via a massive production of reactive oxygen species (ROS) and the release of neutrophil extracellular traps (NETs). We investigated neutrophil-mediated mechanisms of damage in non-vascular BS manifestations and explored in vitro the effects of colchicine in counteracting these mechanisms. Methods: NETs and intracellular ROS production was assessed in blood samples from 80 BS patients (46 with active non-vascular BS, 34 with inactive disease) and 80 healthy controls. Moreover, isolated neutrophils were incubated for 1 hour with an oxidating agent (2,2′-azobis (2-amidinopropane) dihydrochloride; 250nM), and the ability of pure colchicine pre-treatment (100ng/ml) to counteract oxidation-induced damage was assessed. Results: Patients with active non-vascular BS had remarkably increased NET levels [21.2 (IQR 18.3-25.9) mU/ml] compared to patients with inactive disease [16.8 (13.3-20.2) mU/ml] and to controls [7.1 (5.1-8.7) mU/ml], p<0.001]. Also, intracellular ROS tended to be increased in active BS, although not significantly. In active non-vascular BS, NETs correlated with neutrophils ROS production (p<0.001) and were particularly increased in patients with active mucosal (p<0.001), articular (p=0.004), and gastrointestinal symptoms (p=0.006). On isolated neutrophils, colchicine significantly reduced oxidation-induced NET production and cell apoptosis, though not via an antioxidant activity. Conclusion: Neutrophil-mediated mechanisms might be directly involved in non-vascular BS, and NETs, more than ROS, might drive the pathogenesis of mucosal, articular and intestinal manifestations. Colchicine might be effective to counteract neutrophils-mediated damage in BS, although further studies are needed.