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Dupilumab for relapsing or refractory sinonasal and/or asthma manifestations in eosinophilic granulomatosis with polyangiitis: a European retrospective study
  1. Berengere Molina1,
  2. Roberto Padoan2,
  3. Maria Letizia Urban3,
  4. Pavel Novikov4,
  5. Marco Caminati5,
  6. Camille Taillé6,
  7. Antoine Néel7,
  8. Laurence Bouillet8,9,
  9. Paolo Fraticelli10,
  10. Nicolas Schleinitz11,
  11. Christine Christides12,
  12. Laura Moi13,
  13. Bertrand Godeau14,
  14. Ann Knight15,
  15. Jan Walter Schroeder16,
  16. Sylvain Marchand-Adam17,
  17. Helder Gil18,
  18. Vincent Cottin19,
  19. Cécile-Audrey Durel20,
  20. Elena Gelain21,
  21. Boris Lerais22,
  22. Marc Ruivard23,
  23. Matthieu Groh24,
  24. Maxime Samson25,26,
  25. Luca Moroni27,
  26. Jens Thiel28,29,
  27. Anna Kernder30,
  28. Jan Willem Cohen Tervaert31,32,
  29. Giulia Costanzo33,
  30. Marco Folci34,
  31. Sonia Rizzello35,
  32. Pascal Cohen36,
  33. Giacomo Emmi3,37,
  34. Benjamin Terrier1
  1. 1 Department of Internal Medicine, Hospital Cochin, Paris, France
  2. 2 Division of Rheumatology, Department of Medicine DIMED, University of Padua, Padova, Italy
  3. 3 Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
  4. 4 Tareev Clinic of Internal Diseases, I M Sechenov First Moscow State Medical University, Moskva, Russian Federation
  5. 5 Department of Medicine, Asthma, Allergy and Clinical Immunology, University of Verona, Verona, Italy
  6. 6 Department of Respiratory Diseases, Bichat Hospital, APHP Nord-Université Paris-Cité, Paris, France
  7. 7 Department of Internal Medicine, Nantes University Hospital, Nantes, France
  8. 8 T-reg unit, CNRS, UMR 5525, VetAgro Sup, Grenoble Alpes University Hospital, Grenoble, France
  9. 9 Internal Medicine Department, Grenoble University Hospital, Grenoble, France
  10. 10 Internal Medicine department, University Hospital Ospedali Riuniti, Ancona, Italy
  11. 11 Department of Internal Medicine, Timone Hospital AP-HM, Aix-Marseille University, Marseille, France
  12. 12 Department of Internal Medicine, Avignon Hospital, Avignon, France
  13. 13 Immunology and Allergology, Institut Central des Hôpitaux, Valais Hospital, Sion, Switzerland
  14. 14 Department of Internal Medicine, Henri Mondor University Hospital, Creteil, France
  15. 15 Rheumatology, Institute of Medical Sciences, Uppsala University, Uppsala, Sweden
  16. 16 Unit of Allergology and Immunology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
  17. 17 Department of Respiratory Medicine, Regional University Hospital Centre, Tours, France
  18. 18 Department of Internal Medicine, Besancon University Hospital, Besancon, France
  19. 19 Coordinating Reference Center for Rare Pulmonary Disease, Department of Respiratory Medicine, Louis Pradel Hospital, Bron, France
  20. 20 Department of Internal Medicine, University Hospital Edouard Herriot, HCL, Lyon, France
  21. 21 Nephrology and Dialysis Unit, Meyer Children's Hospital, Florence, Italy
  22. 22 Department of Internal Medicine, Brest University Hospital, Brest, France
  23. 23 Internal Medicine, University Hospital Centre, Clermont-Ferrand, France
  24. 24 National Referral Center for Hypereosinophilic Syndrome (CEREO), Department of Internal Medicine, Foch Hospital, Suresnes, France
  25. 25 Department of Internal Medicine and Clinical Immunology, University Hospital Centre, Dijon, France
  26. 26 INSERM, EFS BFC, UMR1098, RIGHT Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, University of Bourgogne Franche-Comté, Dijon, France
  27. 27 Unit of Immunology, Rheumatology, Allergy, and Rare Diseases (UnIRAR), San Raffaele Scientific Institute, Milan, Italy
  28. 28 Department of Rheumatology and Clinical Immunology, Medical Center, University of Freiburg, Freiburg, Germany
  29. 29 Division of Rheumatology and Clinical Immunology, Department of Internal Medicine, Medical University, Graz, Austria
  30. 30 Department Rheumatology & Hiller-Research Unit Rheumatology, Heinrich-Heine-University Düsseldorf, Medical Faculty, Dusseldorf, Germany
  31. 31 Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
  32. 32 School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands
  33. 33 Department of Medical Sciences and Public Health, University of Cagliari, Monserrato, Italy
  34. 34 Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy
  35. 35 Severe Asthma Unit, Careggi University Hospital, Florence, Italy
  36. 36 Department of Internal Medicine, Cochin Hospital, Paris, France
  37. 37 Centre for Inflammatory Diseases, Department of Medicine, Monash Medical Centre, Monash University, Clayton, Victoria, Australia
  1. Correspondence to Dr Benjamin Terrier, Department of Internal Medicine, Hospital Cochin, Paris 75014, Île-de-France, France; benjamin.terrier{at}


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.

  • Systemic vasculitis
  • Immune System Diseases
  • Biological Therapy
  • Autoimmune Diseases
  • Therapeutics

Data availability statement

Data are available on reasonable request.

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  • Handling editor Josef S Smolen

  • Twitter @#OrphaLung, @Maxime_Samson21

  • Contributors Data collection and analysis was performed by BM and BT. The first draft of the manuscript was written by BM and BT. All authors commented on previous versions of the manuscript and approved the final manuscript. BT is responsible for the overall content as guarantor.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.