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.

Body fat has regulatory functions through producing cytokines and adipokines whose role in the pathogenesis of Systemic Sclerosis (SSc) is currently emerging. Changes in body mass, either overweight or underweight status, entail a dysregulation of the cytokines/adipokines network that may impact on SSc disease activity. We evaluated serum levels of adipokines and cytokines in SSc patients and correlated them to clinical features and body mass index (BMI) categories. The study included 89 SSc patients and 26 healthy donors (HD). Serum levels of adiponectin, leptin, resistin, visfatin, TNFα, IFNγ, IL-2, IL-10, and IL-17A were measured by Multiplex Immunoassay, and correlated to BMI, waist to hip ratio, and disease specific features. Mann-Whitney U-test or t-Student for unpaired data, Kruskal-Wallis test or ANOVA, were used for comparisons between groups. Spearman’s or Pearson’s test were used for correlation analysis. Serum levels of TNFα, IL-2, leptin, and resistin, were significantly higher in SSc than in HD. The highest levels of IL-17A, IL-2, IL-10, leptin and visfatin were detected in obese SSc patients (p <0.01). Conversely, underweight SSc patients showed the highest TNFα levels (p<0.05), which were negatively correlated with BMI (p=0.05). No correlation between adipokines/cytokines and clinical characteristics was found. Adipokines, IL-2, IL-10 and IL-17A were found to be increased in obese SSc patients, but whether they play a role in the pathogenesis of the disease remains to be investigated. Intriguingly, underweight patients had higher TNFα levels, suggesting a potential role of TNFα in inducing the cachexia observed in long-lasting disease.