BENRALIZUMAB FOR EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS (EGPA): RESULTS FROM A EUROPEAN MULTICENTER STUDY ON 121 PATIENTS

A. Bettiol, I. Mattioli, M. L. Urban, F. Bello, R. Padoan, M. Groh, G. Lopalco, A. Egan, V. Cottin, P. Fraticelli, C. Crimi, S. Del Giacco, J. Schroeder, L. Moi, D. Jayne, A. Vaglio, G. EmmiUniversity of Florence, Department of Experimental and Clinical Medicine, Florence, Italy University of Padova, Department of Medicine DIMED, Padova, Italy Hôpital Foch, Department of Internal Medicine, Suresnes, France University of Bari, Department of Precision and Rigenerative Medicine and Ionian Area, Bari, Italy Addenbrookes Hospital, Department of Medicine, Cambridge, United Kingdom Hospices Civils de Lyon, University of Lyon, National Reference Centre for Rare Pulmonary Diseases, Lyon, France Marche University Hospital, Clinica Medica, Ancona, Italy University of Catania, Department of Clinical and Experimental Medicine, Catania, Italy University of Cagliari, Department of Medical Sciences and Public Health, Cagliari, Italy Niguarda Hospital, Unit of Allergy and Clinical Immunology, Milano, Italy Centre Hospitalier Universitaire Vaudois, Department of Medicine, Lausanne, Switzerland University of Cambridge, Department of Medicine, Cambridge, United Kingdom University of Florence and Meyer Children’s Hospital, Department of Biomedical, Experimental and Clinical Sciences “Mario Serio”, Florence, Italy  Background Eosinophilic granulomatosis with polyangiitis (EGPA) is an ANCA-associated vasculitis characterized by asthma, ear-nose-throat (ENT) manifestations, peripheral hypereosinophilia and systemic vasculitic involvement [1]. Increased serum levels of interleukin 5 (IL-5) have been observed in eosinophilic disorders, including EGPA, and a genome-wide association study identified the IL-5 region as a major EGPA-associated loci [2]. On these bases, an increasing interest is focusing on benralizumab (an IL-5 receptor antagonist approved for severe eosinophilic asthma at the dosage of 30mg every 4 weeks for 3 administrations, then every 8 weeks) as a new potential therapy for EGPA. Following the promising results of a pilot study on 10 patients [3], a randomized double-blind trial is ongoing to assess the efficacy and safety of benralizumab at a higher dosage (30mg/4 weeks), as compared to mepolizumab (another IL-5 inhibitor approved for EGPA) in patients with EGPA (NCT04157348). In the meanwhile, isolated cases of patients with refractory EGPA, successfully treated with benralizumab, have been described in the literature [4,5]. Objectives This study aimed to assess the efficacy and safety of benralizumab in a multicenter European cohort of patients with EGPA. Methods The study included patients with EGPA treated with benralizumab at 28 centers belonging to the European EGPA Study Group. Efficacy and safety outcomes were assessed after 3, 6 and 12 months of treatment. Complete response (CR) was defined as no disease activity (Birmingham Vasculitis Activity Score [BVAS] = 0) and a daily prednisone equivalent dose ≤4 mg. Respiratory outcomes included asthma, ENT manifestations and lung function. Results A cohort of 121 patients with EGPA was included. All were treated with benralizumab at the dosage approved for eosinophilic asthma (30mg every 4 weeks for 3 administrations, then every 8 weeks). The proportion of patients meeting the criteria for CR was 16% at 3 months, 26% at 6 months and 46% at 12 months of follow-up (Table 1). During follow-up, a drop in BVAS was recorded, from a median score of 3 (IQR 2-8) at baseline to 0 (0-2) at month 3 and 6 and to 0 (0-1) at month 12 (p<0.001 at all timepoints). Regarding respiratory outcomes, the proportion of patients reporting active asthmatic decreased from 94% at baseline to 39% at 3 months (p<0.001), and that of patients with active ENT manifestations decreased from 70% at baseline to 49% at 3 months (p<0.001), with concomitant improvements in lung function. 19 patients experienced adverse events, three requiring hospitalization. Conclusion The results from this large European real-world study suggest that benralizumab, at the dosage approved for severe eosinophilic asthma, could be effective and safe to control respiratory EGPA manifestations and overall disease activity. References Trivioli, Rheumatol 2020 Lyon, Nat Commun 2019 Guntur, JACI Pract 2021 Bormioli, JIACI 2021 Menzella, Multidisciplinary Respir Med 2021 Table 1. Efficacy outcomes Benralizumab beginning (t0) 3 months p-value (t3 vs t0) 6 months p-value (t6 vs t0) 12 months p-value (t12 vs t0) N patients 121 121 101 85 Complete response - 15/96 (15.6%) 23/87 (26.4%) 32/69 (46.4%) BVAS, median (IQR) 3 (2-8) 0 (0-2)[n=96] <0.001* 0 (0-2)[n=87] <0.001* 0 (0-1)[n=69] <0.001* Respiratory involvement Pulmonary 114 (94.2) 43/111 (38.7) <0.001* 36 (35.6) <0.001* 33 (38.8) <0.001* ENT 85 (70.3) 54/111 (48.6) <0.001* 46 (45.5) <0.001* 40 (47.1) <0.001* BVAS= Birmingham Vasculitis Activity Score; ENT= ear-nose-throat; IQR= interquartile range. Acknowledgements We acknowledge drs./profs. Francesco Cinetto, Marco Caminati, Pavel Novikov, Alvise Berti, Paolo Cameli, Pascal Cathébras, Angelo Coppola, Cécile-Audrey Durel, Marco Folci, Alberto Lo Gullo, Carlo Lombardi, Sara Monti, Paola Parronchi, Carlos Martinez Rivera, Roser Solans, Angelo Vacca, Maria Cinta Cid, and Domenico Prisco, who contributed to this study. Disclosure of Interests Alessandra Bettiol: None declared, Irene Mattioli: None declared, Maria Letizia Urban: None declared, Federica Bello: None declared, Roberto Padoan Consultant of: GSK, Matthieu Groh: None declared, Giuseppe Lopalco: None declared, Allyson Egan: None declared, Vincent Cottin Consultant of: Astra Zeneca and GSK., Paolo Fraticelli: None declared, Claudia Crimi Speakers bureau: Honoraria for lectures from GSK, Sanofi, Astra Zeneca, Novartis, Resmed, Fisher & Paykel., Stefano Del Giacco: None declared, Jan Schroeder: None declared, Laura Moi: None declared, David Jayne Consultant of: Astra-Zeneca, Aurinia, BMS, Boehringer-Ingelheim, Chemocentryx, Chugai, CSL, GSK, Infla-RX, Janssen, Novartis, Roche/Genentech, Takeda and Vifor, Augusto Vaglio Consultant of: GSK, Giacomo Emmi Consultant of: GSK. Keywords: Real-world evidence, bDMARD, Vasculitis DOI: 10.1136/annrheumdis-2023-eular.1510Citation: , volume 82, supplement 1, year 2023, page 196Session: ANCA-associated vasculitis (Oral Presentations)