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

Molina B.;Padoan R.;Urban M. L.;Novikov P.;Caminati M.;Taillé C.;Néel A.;Bouillet L.;Fraticelli P.;Schleinitz N.;Christides C.;Moi L.;Godeau B.;Knight A.;Schroeder J. W.;Marchand-Adam S.;Gil H.;Cottin V.;Durel C. A.;Gelain E.;Lerais B.;Ruivard M.;Groh M.;Samson M.;Moroni L.;Thiel J.;Kernder A.;Cohen Tervaert J. W.;Costanzo G.

Writing - Review & Editing

;Folci M.;Rizzello S.;Cohen P.;Emmi G.;Terrier B.

2023-01-01

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Abstract

Background Eosinophilic 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 methods We 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.Results Fifty-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.Conclusion These 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.