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

Berengere Molina¹, Roberto Padoan², Maria Letizia Urban³, Pavel Novikov⁴, Marco Caminati⁵, Camille Taillé⁶, Antoine Néel⁷, Laurence Bouillet^{8

9}, Paolo Fraticelli¹⁰, Nicolas Schleinitz¹¹, Christine Christides¹², Laura Moi¹³, Bertrand Godeau¹⁴, Ann Knight¹⁵, Jan Walter Schroeder¹⁶, Sylvain Marchand-Adam¹⁷, Helder Gil¹⁸, Vincent Cottin¹⁹, Cécile-Audrey Durel²⁰, Elena Gelain²¹, Boris Lerais²², Marc Ruivard²³, Matthieu Groh²⁴, Maxime Samson^{25

26}, Luca Moroni²⁷, Jens Thiel^{28

29}, Anna Kernder³⁰, Jan Willem Cohen Tervaert^{31

32}, Giulia Costanzo³³, Marco Folci³⁴, Sonia Rizzello³⁵, Pascal Cohen³⁶, Giacomo Emmi^{3

37}, Benjamin Terrier³⁸

Affiliations

¹ Department of Internal Medicine, Hospital Cochin, Paris, France.
² Division of Rheumatology, Department of Medicine DIMED, University of Padua, Padova, Italy.
³ Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
⁴ Tareev Clinic of Internal Diseases, I M Sechenov First Moscow State Medical University, Moskva, Russian Federation.
⁵ Department of Medicine, Asthma, Allergy and Clinical Immunology, University of Verona, Verona, Italy.
⁶ Department of Respiratory Diseases, Bichat Hospital, APHP Nord-Université Paris-Cité, Paris, France.
⁷ Department of Internal Medicine, Nantes University Hospital, Nantes, France.
⁸ T-reg unit, CNRS, UMR 5525, VetAgro Sup, Grenoble Alpes University Hospital, Grenoble, France.
⁹ Internal Medicine Department, Grenoble University Hospital, Grenoble, France.
¹⁰ Internal Medicine department, University Hospital Ospedali Riuniti, Ancona, Italy.
¹¹ Department of Internal Medicine, Timone Hospital AP-HM, Aix-Marseille University, Marseille, France.
¹² Department of Internal Medicine, Avignon Hospital, Avignon, France.
¹³ Immunology and Allergology, Institut Central des Hôpitaux, Valais Hospital, Sion, Switzerland.
¹⁴ Department of Internal Medicine, Henri Mondor University Hospital, Creteil, France.
¹⁵ Rheumatology, Institute of Medical Sciences, Uppsala University, Uppsala, Sweden.
¹⁶ Unit of Allergology and Immunology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
¹⁷ Department of Respiratory Medicine, Regional University Hospital Centre, Tours, France.
¹⁸ Department of Internal Medicine, Besancon University Hospital, Besancon, France.
¹⁹ Coordinating Reference Center for Rare Pulmonary Disease, Department of Respiratory Medicine, Louis Pradel Hospital, Bron, France.
²⁰ Department of Internal Medicine, University Hospital Edouard Herriot, HCL, Lyon, France.
²¹ Nephrology and Dialysis Unit, Meyer Children's Hospital, Florence, Italy.
²² Department of Internal Medicine, Brest University Hospital, Brest, France.
²³ Internal Medicine, University Hospital Centre, Clermont-Ferrand, France.
²⁴ National Referral Center for Hypereosinophilic Syndrome (CEREO), Department of Internal Medicine, Foch Hospital, Suresnes, France.
²⁵ Department of Internal Medicine and Clinical Immunology, University Hospital Centre, Dijon, France.
²⁶ INSERM, EFS BFC, UMR1098, RIGHT Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, University of Bourgogne Franche-Comté, Dijon, France.
²⁷ Unit of Immunology, Rheumatology, Allergy, and Rare Diseases (UnIRAR), San Raffaele Scientific Institute, Milan, Italy.
²⁸ Department of Rheumatology and Clinical Immunology, Medical Center, University of Freiburg, Freiburg, Germany.
²⁹ Division of Rheumatology and Clinical Immunology, Department of Internal Medicine, Medical University, Graz, Austria.
³⁰ Department Rheumatology & Hiller-Research Unit Rheumatology, Heinrich-Heine-University Düsseldorf, Medical Faculty, Dusseldorf, Germany.
³¹ Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
³² School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands.
³³ Department of Medical Sciences and Public Health, University of Cagliari, Monserrato, Italy.
³⁴ Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy.
³⁵ Severe Asthma Unit, Careggi University Hospital, Florence, Italy.
³⁶ Department of Internal Medicine, Cochin Hospital, Paris, France.
³⁷ Centre for Inflammatory Diseases, Department of Medicine, Monash Medical Centre, Monash University, Clayton, Victoria, Australia.
³⁸ Department of Internal Medicine, Hospital Cochin, Paris, France benjamin.terrier@aphp.fr.

PMID: 37734881
DOI: 10.1136/ard-2023-224756

Observational Study

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

Berengere Molina et al. Ann Rheum Dis. 2023 Dec.

. 2023 Dec;82(12):1587-1593.

doi: 10.1136/ard-2023-224756. Epub 2023 Sep 21.

Authors

Affiliations

¹ Department of Internal Medicine, Hospital Cochin, Paris, France.
² Division of Rheumatology, Department of Medicine DIMED, University of Padua, Padova, Italy.
³ Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
⁴ Tareev Clinic of Internal Diseases, I M Sechenov First Moscow State Medical University, Moskva, Russian Federation.
⁵ Department of Medicine, Asthma, Allergy and Clinical Immunology, University of Verona, Verona, Italy.
⁶ Department of Respiratory Diseases, Bichat Hospital, APHP Nord-Université Paris-Cité, Paris, France.
⁷ Department of Internal Medicine, Nantes University Hospital, Nantes, France.
⁸ T-reg unit, CNRS, UMR 5525, VetAgro Sup, Grenoble Alpes University Hospital, Grenoble, France.
⁹ Internal Medicine Department, Grenoble University Hospital, Grenoble, France.
¹⁰ Internal Medicine department, University Hospital Ospedali Riuniti, Ancona, Italy.
¹¹ Department of Internal Medicine, Timone Hospital AP-HM, Aix-Marseille University, Marseille, France.
¹² Department of Internal Medicine, Avignon Hospital, Avignon, France.
¹³ Immunology and Allergology, Institut Central des Hôpitaux, Valais Hospital, Sion, Switzerland.
¹⁴ Department of Internal Medicine, Henri Mondor University Hospital, Creteil, France.
¹⁵ Rheumatology, Institute of Medical Sciences, Uppsala University, Uppsala, Sweden.
¹⁶ Unit of Allergology and Immunology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
¹⁷ Department of Respiratory Medicine, Regional University Hospital Centre, Tours, France.
¹⁸ Department of Internal Medicine, Besancon University Hospital, Besancon, France.
¹⁹ Coordinating Reference Center for Rare Pulmonary Disease, Department of Respiratory Medicine, Louis Pradel Hospital, Bron, France.
²⁰ Department of Internal Medicine, University Hospital Edouard Herriot, HCL, Lyon, France.
²¹ Nephrology and Dialysis Unit, Meyer Children's Hospital, Florence, Italy.
²² Department of Internal Medicine, Brest University Hospital, Brest, France.
²³ Internal Medicine, University Hospital Centre, Clermont-Ferrand, France.
²⁴ National Referral Center for Hypereosinophilic Syndrome (CEREO), Department of Internal Medicine, Foch Hospital, Suresnes, France.
²⁵ Department of Internal Medicine and Clinical Immunology, University Hospital Centre, Dijon, France.
²⁶ INSERM, EFS BFC, UMR1098, RIGHT Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, University of Bourgogne Franche-Comté, Dijon, France.
²⁷ Unit of Immunology, Rheumatology, Allergy, and Rare Diseases (UnIRAR), San Raffaele Scientific Institute, Milan, Italy.
²⁸ Department of Rheumatology and Clinical Immunology, Medical Center, University of Freiburg, Freiburg, Germany.
²⁹ Division of Rheumatology and Clinical Immunology, Department of Internal Medicine, Medical University, Graz, Austria.
³⁰ Department Rheumatology & Hiller-Research Unit Rheumatology, Heinrich-Heine-University Düsseldorf, Medical Faculty, Dusseldorf, Germany.
³¹ Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
³² School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands.
³³ Department of Medical Sciences and Public Health, University of Cagliari, Monserrato, Italy.
³⁴ Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy.
³⁵ Severe Asthma Unit, Careggi University Hospital, Florence, Italy.
³⁶ Department of Internal Medicine, Cochin Hospital, Paris, France.
³⁷ Centre for Inflammatory Diseases, Department of Medicine, Monash Medical Centre, Monash University, Clayton, Victoria, Australia.
³⁸ Department of Internal Medicine, Hospital Cochin, Paris, France benjamin.terrier@aphp.fr.

PMID: 37734881
DOI: 10.1136/ard-2023-224756

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.

Keywords: Autoimmune Diseases; Biological Therapy; Immune System Diseases; Systemic vasculitis; Therapeutics.

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Conflict of interest statement

Competing interests: None declared.

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Research Materials

Miscellaneous