Dupilumab for relapsing or refractory sinonasal and/or asthma manifestations in eosinophilic granulomatosis with polyangiitis: a European retrospective study

• Published in: Annals of the rheumatic diseases Vol. 82; no. 12; pp. 1587 - 1593
• Main Authors: Molina, Berengere, Padoan, Roberto, Urban, Maria Letizia, Novikov, Pavel, Caminati, Marco, Taillé, Camille, Néel, Antoine, Bouillet, Laurence, Fraticelli, Paolo, Schleinitz, Nicolas, Christides, Christine, Moi, Laura, Godeau, Bertrand, Knight, Ann, Schroeder, Jan Walter, Marchand-Adam, Sylvain, Gil, Helder, Cottin, Vincent, Durel, Cécile-Audrey, Gelain, Elena, Lerais, Boris, Ruivard, Marc, Groh, Matthieu, Samson, Maxime, Moroni, Luca, Thiel, Jens, Kernder, Anna, Cohen Tervaert, Jan Willem, Costanzo, Giulia, Folci, Marco, Rizzello, Sonia, Cohen, Pascal, Emmi, Giacomo, Terrier, Benjamin
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and European League Against Rheumatism 01.12.2023; BMJ Publishing Group LTD
• Subjects: Asthma; Autoimmune Diseases; Biological Therapy; Cytokines; Cytoplasm; Eosinophilia; Granulomatosis; Immune System Diseases; Immunosuppressive agents; Inflammatory diseases; Interleukin 5 receptors; Leukocytes (eosinophilic); Monoclonal antibodies; Nose; Patients; Prednisone; Systemic vasculitis; Therapeutics; Vasculitis; Vein & artery diseases; France
• ISSN: 0003-4967; 1468-2060; 1468-2060
• DOI: 10.1136/ard-2023-224756

BackgroundEosinophilic granulomatosis with polyangiitis (EGPA) is often associated with glucocorticoid-dependent asthma and/or ear, nose and throat (ENT) manifestations. When immunosuppressants and/or mepolizumab are ineffective, dupilumab could be an option. We describe the safety and efficacy of off-label use of dupilumab in relapsing and/or refractory EGPA.Patients and methodsWe conducted an observational multicentre study of EGPA patients treated with dupilumab. Complete response was defined by Birmingham Vasculitis Activity Score (BVAS)=0 and prednisone dose ≤4 mg/day, and partial response by BVAS=0 and prednisone dose >4 mg/day. Eosinophilia was defined as an eosinophil count >500/mm3.ResultsFifty-one patients were included. The primary indication for dupilumab was disabling ENT symptoms in 92%. After a median follow-up of 13.1 months, 18 patients (35%) reported adverse events (AEs), including two serious AEs. Eosinophilia was reported in 34 patients (67%), with a peak of 2195/mm3 (IQR 1268–4501) occurring at 13 weeks (IQR 4–36) and was associated with relapse in 41%. Twenty-one patients (41%) achieved a complete response and 12 (24%) a partial response. Sixteen (31%) patients experienced an EGPA relapse while on dupilumab, which was associated with blood eosinophilia in 14/16 (88%) patients. The median eosinophil count at the start of dupilumab was significantly lower in relapsers than in non-relapsers, as was the median time between stopping anti-IL-5/IL-5R and switching to dupilumab.ConclusionThese results suggest that dupilumab may be effective in treating patients with EGPA-related ENT manifestations. However, EGPA flares occurred in one-third of patients and were preceded by eosinophilia in 88%, suggesting that caution is required.