Dupilumab for Relapsing or Refractory Eosinophilic Granulomatosis with Polyangiitis: A European Retrospective Study

Berengere Molina¹, Roberto Padoan², Maria Letizia Urban³, Pavel Novikov⁴, Marco Caminati⁵, Camille Taillé⁶, Antoine Néel⁷, Laurence Bouillet⁸, Paolo Fraticelli⁹, Nicolas Schleinitz¹⁰, Christine Christides¹¹, Laura Moi¹², Bertrand Godeau¹³, Ann Knight¹⁴, Jan Walter Schroeder¹⁵, Sylvain Marchand-Adam¹⁶, Helder Gil¹⁷, Vincent Cottin¹⁸, Cécile-Audrey Durel¹⁹, Elena Gelain²⁰, Boris Lerais²¹, Marc Ruivard²², Matthieu Groh²³, Maxime Samson²⁴, Luca Moroni²⁵, Jens Thiel²⁶, Anna Kernder²⁷, Jan Willem Cohen Tervaert²⁸, Giulia Costanzo²⁹, Marco Folci³⁰, Sonia Rizzello³¹, Pascal Cohen³², Giacomo Emmi³³ and Benjamin Terrier³⁴, ¹Cochin Hospital, Paris, France, ²Department of Medicine DIMED, University of Padova, Padova, Italy, ³Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy, ⁴Sechenov First Moscow State Medical University, Moscow, Russia, ⁵University of Verona, Verona, Italy, ⁶AP-HP, Bichat Hospital, Reference Center for Rare Pulmonary Diseases and University of Paris Cité, Inserm 1152, Paris, France, ⁷CHU Nantes, Nantes, France, ⁸Internal medicine department, Grenoble University Hospital, Grenoble, France, ⁹University Hospital Ospedali Riuniti, Ancona, Italy, ¹⁰Aix Marseille university, AP-HM, Marseille, France, ¹¹Avignon Hospital, Avignon, France, ¹²Valais Hospital, Sion, Switzerland, ¹³CHU Henri Mondor, Créteil, France, ¹⁴Uppsala University, Uppsala, Sweden, ¹⁵ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy, ¹⁶CHRU Tours, service de pneumologie et d'explorations fonctionnelles respiratoires, Tours, France, ¹⁷CHU Besancon, Besançon, France, ¹⁸Coordinating Reference Center for Rare Pulmonary Diseases, Louis Pradel Hospital, University of Lyon, INRAE, Lyon, France, ¹⁹CHU Lyon, Lyon, France, ²⁰Meyer Children's Hospital, Florence, Italy, ²¹Brest University Hospital, Brest, France, ²²CHU Clermont Ferrand, Clermont Ferrand, France, ²³National Referral Center for Hypereosinophilic Syndrome (CEREO), Hôpital Foch, Suresnes, France, ²⁴Department of Internal Medicine and Clinical Immunology, Dijon University Hospital, Dijon, France, ²⁵San Raffaele Scientific Institute, Milan, Italy, ²⁶University Hospital Freiburg, Freiburg, Germany, ²⁷Heinrich-Heine-University Düsseldorf, Dusseldorf, Germany, ²⁸University of Alberta, Edmonton, AB, Canada, ²⁹University of Cagliari, Monserrato, Italy, ³⁰Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy, ³¹Careggi University Hospital, Florence, Italy, ³²CHU Cochin, Paris, France, ³³University of Florence, Florence, Italy, ³⁴Department of Internal Medicine, Hôpital Cochin, AP-HP, Paris, France

Meeting: ACR Convergence 2023

Keywords: ANCA associated vasculitis, Biologicals, cytokines, Eosinophilic Granulomatosus with Polyangiitis (Churg-Strauss), Therapy, alternative

Session Information

Date: Sunday, November 12, 2023

Title: Abstracts: Vasculitis – ANCA-Associated I

Session Type: Abstract Session

Session Time: 4:00PM-5:30PM

Background/Purpose: Eosinophilic granulomatosis with polyangiitis (EGPA) is an ANCA-associated vasculitides characterized by asthma, blood and tissue eosinophilia and systemic manifestations. Glucocorticoids (GCs)-dependent asthma and/or disabling ear, nose and throat (ENT) symptoms may persist in half of the patients. Mepolizumab represent an important strategy in these situations. Nevertheless, some patients may show poor or dissociated response between asthma and ENT involvement, requiring alternative options. Dupilumab, a monoclonal antibody directed against the IL-4/IL-13 receptor, has been approved for the treatment of eosinophilic asthma and chronic rhinosinusitis with nasal polyposis, raising the question of its efficacy and its tolerance in EGPA. We aimed to describe the safety and efficacy of the off-label use of dupilumab to treat relapsing and/or refractory EGPA.

Methods: We conducted a European multicenter retrospective study including patients with EGPA fulfilling 2022 ACR/EULAR classification criteria and treated with dupilumab. We collected safety and efficacy data. Response was defined as complete by BVAS=0 and prednisone dose ≤4 mg/day, and partial by BVAS=0 and prednisone dose >4 mg/d

Results: Fifty patients were included, with a median age of 52 years (IQR, 45-57), 29 were women (58%). Dupilumab was initiated for disabling ENT manifestations in 41 (82%) cases, GCs-dependency in 28 (56%) and/or poorly controlled asthma in 27 (54%). Dupilumab was associated with methotrexate in 5, azathioprine in 3, and mycophenolate in 1. Median follow-up after dupilumab initiation was 13.2 (5.4-17.8) months.

Twenty-one patients (42%) achieved a complete response and 12 (24%) a partial response. Median BVAS was 2 (1-4) at dupilumab initiation and dropped to 0 (0-1.5) at 12 months (p=0.01). Baseline prednisone dose was 8 mg/d (5-13.8) and decreased to 2.5 mg/d (0-5) at 12 months (p=0.04).

Seventeen (34%) patients reported adverse events (AE). Main AE were mild-to-moderate and included headache (n=4), injection-site reaction (n=3), myalgia (n=3), arthralgia (n=3). Two patients experienced non-fatal anaphylactic shock. Dupilumab-induced eosinophilia was reported in 33 patients (66%), with a median peak eosinophil count of 1980/mm3 (IQR 560-9800) occurring 13 weeks (IQR 5-18) after starting dupilumab. This dupilumab-induced eosinophilia remained asymptomatic in 42% cases.

Fifteen (30%) patients presented a EGPA flarewhich was associated with blood eosinophilia in 13/15 (87%) cases leading to dupilumab discontinuation in 11 cases (73%), including systemic flares in 7 cases, asthma exacerbation in 6 cases, ENT relapse in 1 and inflammatory arthralgia in 1.

In total, 21 (42%) patients discontinued dupilumab: vasculitis flare (n=11), dupilumab-induced eosinophilia (n=7), anaphylactic shock (n=2), cancer (n=1). No deaths were reported.

Conclusion: These results suggest that dupilumab may be effective in relapsing and/or refractory EGPA, particularly in ENT manifestations. However, dupilumab-induced eosinophilia is common and may remain asymptomatic or be associated with relapse, so caution is warranted.

Disclosures: B. Molina: None; R. Padoan: GlaxoSmithKlein(GSK), 6; M. Urban: None; P. Novikov: None; M. Caminati: None; C. Taillé: AstraZeneca, 6, Chiesi, 5, 6, GSK, 5, 6, Novartis, 5, 6, Sanofi, 6; A. Néel: None; L. Bouillet: None; P. Fraticelli: None; N. Schleinitz: CSL behring, 1, Eusapharma, 6, GSK, 6; C. Christides: None; L. Moi: None; B. Godeau: None; A. Knight: None; J. Schroeder: None; S. Marchand-Adam: None; H. Gil: None; V. Cottin: Boehringer Ingelheim, 2, 5, 6, 12, Support for attending meetings, Celgene/BMS, 1, 2, CSL Behring, 2, Ferrer, 2, 6, 12, Support for attending meetings, FibroGen, 1, Galapagos, 1, 2, Galecto, 1, GlaxoSmithKline, 2, Pliant, 2, Pure Tech, 2, Redx, 2, Roche, 1, 2, 6, 12, Support for attending meetings, Sanofi, 2, Shionogi, 2; C. Durel: None; E. Gelain: None; B. Lerais: None; M. Ruivard: None; M. Groh: AstraZeneca, 6, GSK, 6, Sanofi, 6; M. Samson: ARGENX, 2, Boehringer-Ingelheim, 2, CHUGAI, 2, CSL Vifor, 2, GlaxoSmithKlein(GSK), 2, NOVARTIS, 2, 5; L. Moroni: None; J. Thiel: None; A. Kernder: None; J. Tervaert: None; G. Costanzo: None; M. Folci: None; S. Rizzello: None; P. Cohen: None; G. Emmi: AstraZeneca, 2, Boehringer-Ingelheim, 2, GlaxoSmithKlein(GSK), 2, Novartis, 2, Sanofi, 2, Sobi, 2; B. Terrier: AstraZeneca, 5, CSL Vifor, 2, GlaxoSmithKlein(GSK), 2.

To cite this abstract in AMA style:

Molina B, Padoan R, Urban M, Novikov P, Caminati M, Taillé C, Néel A, Bouillet L, Fraticelli P, Schleinitz N, Christides C, Moi L, Godeau B, Knight A, Schroeder J, Marchand-Adam S, Gil H, Cottin V, Durel C, Gelain E, Lerais B, Ruivard M, Groh M, Samson M, Moroni L, Thiel J, Kernder A, Tervaert J, Costanzo G, Folci M, Rizzello S, Cohen P, Emmi G, Terrier B. Dupilumab for Relapsing or Refractory Eosinophilic Granulomatosis with Polyangiitis: A European Retrospective Study [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/dupilumab-for-relapsing-or-refractory-eosinophilic-granulomatosis-with-polyangiitis-a-european-retrospective-study/. Accessed .

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