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.

Introduction |Shellfish allergy is an important cause of food allergies worldwide. Both in vivo and in vitro diagnostics failure nowadays is caused by the poor quality of the extracts associated with the scarce availability of allergenic molecules in the market. It is known that not all patients with shellfish allergies experience adverse reactions to mollusks. It is still unclear how to detect and diagnose correctly these patients. Aim |To investigate the features of shrimp-allergic patients either reactive or tolerant to mollusks, with the currently available diagnostic methods. Methods| Nineteen centers, scattered throughout Italy, participated in the study, enrolling patients allergic to shrimp with or without associated reactions to mollusks. Patients underwent skin tests using commercial extracts or fresh raw and cooked foods, and IgE reactivity to currently available allergenic extracts and molecules was measured in vitro. Results| Two hundred and forty-seven individuals with a history of adverse reaction to crustaceans participated in the study. Only 47.8% of them reacted after cephalopod or bivalve ingestion. None of the tests used, either in vivo or in vitro, was able to detect all selected patients. Accordingly, a great heterogeneity of results was observed with an agreement between in vivo and in vitro tests ranging between 52% and 62% of cases. Skin tests were able to identify the cephalopod and bivalve reactors (p <0.001), also using fresh cooked or raw food (p <0.001). The reactivity profile of mollusk reactors was dominated by Pen m 1, over Pen m 2 and Pen m 4 compared to the tolerant subjects, but 33% of patients allergic to shellfish were not detected by any of the available molecules. A higher frequency of shrimp hypersensitivity was recorded in northern Italy, while mollusk reactivity was more frequent in the center-south. Conclusion |The current diagnostic methods are inadequate to predict the cross-reactivity between crustaceans and mollusks. The detection of mollusks hypersensitivity must still rely on skin tests with fresh material. There is no need to exclude mollusks from shrimp allergic patients’ diet unless clinical history, the available diagnostic instruments, and/or tolerance tests support such a decision. Primary sensitization to mollusks seems possible.