PMID- 37734881 OWN - NLM STAT- MEDLINE DCOM- 20231113 LR - 20231119 IS - 1468-2060 (Electronic) IS - 0003-4967 (Linking) VI - 82 IP - 12 DP - 2023 Dec TI - Dupilumab for relapsing or refractory sinonasal and/or asthma manifestations in eosinophilic granulomatosis with polyangiitis: a European retrospective study. PG - 1587-1593 LID - 10.1136/ard-2023-224756 [doi] AB - 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. Eosinophilia was defined as an eosinophil count >500/mm(3). 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. CI - (c) Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Molina, Berengere AU - Molina B AUID- ORCID: 0009-0001-4941-9772 AD - Department of Internal Medicine, Hospital Cochin, Paris, France. FAU - Padoan, Roberto AU - Padoan R AD - Division of Rheumatology, Department of Medicine DIMED, University of Padua, Padova, Italy. FAU - Urban, Maria Letizia AU - Urban ML AD - Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy. FAU - Novikov, Pavel AU - Novikov P AD - Tareev Clinic of Internal Diseases, I M Sechenov First Moscow State Medical University, Moskva, Russian Federation. FAU - Caminati, Marco AU - Caminati M AD - Department of Medicine, Asthma, Allergy and Clinical Immunology, University of Verona, Verona, Italy. FAU - Taille, Camille AU - Taille C AD - Department of Respiratory Diseases, Bichat Hospital, APHP Nord-Universite Paris-Cite, Paris, France. FAU - Neel, Antoine AU - Neel A AD - Department of Internal Medicine, Nantes University Hospital, Nantes, France. FAU - Bouillet, Laurence AU - Bouillet L AD - T-reg unit, CNRS, UMR 5525, VetAgro Sup, Grenoble Alpes University Hospital, Grenoble, France. AD - Internal Medicine Department, Grenoble University Hospital, Grenoble, France. FAU - Fraticelli, Paolo AU - Fraticelli P AD - Internal Medicine department, University Hospital Ospedali Riuniti, Ancona, Italy. FAU - Schleinitz, Nicolas AU - Schleinitz N AD - Department of Internal Medicine, Timone Hospital AP-HM, Aix-Marseille University, Marseille, France. FAU - Christides, Christine AU - Christides C AD - Department of Internal Medicine, Avignon Hospital, Avignon, France. FAU - Moi, Laura AU - Moi L AD - Immunology and Allergology, Institut Central des Hopitaux, Valais Hospital, Sion, Switzerland. FAU - Godeau, Bertrand AU - Godeau B AD - Department of Internal Medicine, Henri Mondor University Hospital, Creteil, France. FAU - Knight, Ann AU - Knight A AD - Rheumatology, Institute of Medical Sciences, Uppsala University, Uppsala, Sweden. FAU - Schroeder, Jan Walter AU - Schroeder JW AD - Unit of Allergology and Immunology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy. FAU - Marchand-Adam, Sylvain AU - Marchand-Adam S AD - Department of Respiratory Medicine, Regional University Hospital Centre, Tours, France. FAU - Gil, Helder AU - Gil H AD - Department of Internal Medicine, Besancon University Hospital, Besancon, France. FAU - Cottin, Vincent AU - Cottin V AUID- ORCID: 0000-0002-5591-0955 AD - Coordinating Reference Center for Rare Pulmonary Disease, Department of Respiratory Medicine, Louis Pradel Hospital, Bron, France. FAU - Durel, Cecile-Audrey AU - Durel CA AD - Department of Internal Medicine, University Hospital Edouard Herriot, HCL, Lyon, France. FAU - Gelain, Elena AU - Gelain E AD - Nephrology and Dialysis Unit, Meyer Children's Hospital, Florence, Italy. FAU - Lerais, Boris AU - Lerais B AD - Department of Internal Medicine, Brest University Hospital, Brest, France. FAU - Ruivard, Marc AU - Ruivard M AD - Internal Medicine, University Hospital Centre, Clermont-Ferrand, France. FAU - Groh, Matthieu AU - Groh M AUID- ORCID: 0000-0003-0810-136X AD - National Referral Center for Hypereosinophilic Syndrome (CEREO), Department of Internal Medicine, Foch Hospital, Suresnes, France. FAU - Samson, Maxime AU - Samson M AUID- ORCID: 0000-0002-6547-232X AD - Department of Internal Medicine and Clinical Immunology, University Hospital Centre, Dijon, France. AD - INSERM, EFS BFC, UMR1098, RIGHT Interactions Greffon-Hote-Tumeur/Ingenierie Cellulaire et Genique, University of Bourgogne Franche-Comte, Dijon, France. FAU - Moroni, Luca AU - Moroni L AD - Unit of Immunology, Rheumatology, Allergy, and Rare Diseases (UnIRAR), San Raffaele Scientific Institute, Milan, Italy. FAU - Thiel, Jens AU - Thiel J AD - Department of Rheumatology and Clinical Immunology, Medical Center, University of Freiburg, Freiburg, Germany. AD - Division of Rheumatology and Clinical Immunology, Department of Internal Medicine, Medical University, Graz, Austria. FAU - Kernder, Anna AU - Kernder A AD - Department Rheumatology & Hiller-Research Unit Rheumatology, Heinrich-Heine-University Dusseldorf, Medical Faculty, Dusseldorf, Germany. FAU - Cohen Tervaert, Jan Willem AU - Cohen Tervaert JW AD - Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. AD - School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands. FAU - Costanzo, Giulia AU - Costanzo G AD - Department of Medical Sciences and Public Health, University of Cagliari, Monserrato, Italy. FAU - Folci, Marco AU - Folci M AD - Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy. FAU - Rizzello, Sonia AU - Rizzello S AD - Severe Asthma Unit, Careggi University Hospital, Florence, Italy. FAU - Cohen, Pascal AU - Cohen P AD - Department of Internal Medicine, Cochin Hospital, Paris, France. FAU - Emmi, Giacomo AU - Emmi G AUID- ORCID: 0000-0001-9575-8321 AD - Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy. AD - Centre for Inflammatory Diseases, Department of Medicine, Monash Medical Centre, Monash University, Clayton, Victoria, Australia. FAU - Terrier, Benjamin AU - Terrier B AUID- ORCID: 0000-0001-6612-7336 AD - Department of Internal Medicine, Hospital Cochin, Paris, France benjamin.terrier@aphp.fr. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20230921 PL - England TA - Ann Rheum Dis JT - Annals of the rheumatic diseases JID - 0372355 RN - 420K487FSG (dupilumab) RN - VB0R961HZT (Prednisone) SB - IM MH - Humans MH - *Granulomatosis with Polyangiitis/complications/drug therapy/diagnosis MH - *Churg-Strauss Syndrome/complications/drug therapy MH - Retrospective Studies MH - Prednisone/therapeutic use MH - Treatment Outcome MH - *Asthma/drug therapy/complications MH - *Eosinophilia/drug therapy/complications MH - Recurrence OTO - NOTNLM OT - Autoimmune Diseases OT - Biological Therapy OT - Immune System Diseases OT - Systemic vasculitis OT - Therapeutics COIS- Competing interests: None declared. EDAT- 2023/09/22 00:42 MHDA- 2023/11/13 06:43 CRDT- 2023/09/21 21:23 PHST- 2023/07/24 00:00 [received] PHST- 2023/08/31 00:00 [accepted] PHST- 2023/11/13 06:43 [medline] PHST- 2023/09/22 00:42 [pubmed] PHST- 2023/09/21 21:23 [entrez] AID - ard-2023-224756 [pii] AID - 10.1136/ard-2023-224756 [doi] PST - ppublish SO - Ann Rheum Dis. 2023 Dec;82(12):1587-1593. doi: 10.1136/ard-2023-224756. Epub 2023 Sep 21.