Berengere Molina1, Maria Letizia Urban2, Roberto Padoan3, Pavel Novikov4, Camille Taillé5, Marco Caminati6, Christine Christides7, nicolas schleinitz8, Laura Moi9, Vincent Cottin10, bertrand godeau11, Laurence Bouillet12, Paolo Fraticelli13, Ann Knight14, Jan Walter Schroeder15, Sylvain Marchand-Adam16, Helder Gil17, Elena Gelain18, Giacomo Emmi2 and Benjamin Terrier19, 1Department of Internal Medicine, Cochin Hospital, Paris, France, 2Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy, 3University of Padova, Padova, Italy, 4Tareev’s Clinic, Sechenov First Moscow State Medical University, Moscow, Russia, 5Pulmonology department, Bichat Hospital, Paris, Ile-de-France, France, 6Verona University Hospital, University of Verona, Verona, Italy, 7Avignon hospital, Avignon, France, 8Aix Marseille university, AP-HM, Marseille, France, 9Centre hospitalier universitaire vaudois, Lausanne, Lausanne, Switzerland, 10Coordinating Reference Center for Rare Pulmonary Diseases, Louis Pradel Hospital, University of Lyon, INRAE, Lyon, France, 11Department of Internal Medicine, National Referral Center for Adult's Immune Cytopenias, Mondor Hospital, Créteil, France, 12Grenoble University Hospital, Grenoble, France, 13Department of Internal Medicine, Ospedali Riuniti di Ancona, Ancona, Italy, 14Akademiska sjukhuset, Uppsala, Sweden, 15ASST GOM Niguarda, Milano, Italy, 16Tours University Hospital, Tours, France, 17Besancon University Hospital, Besançon, France, 18Meyer Children’s University Hospital of Firenze, Florence, Italy, 19National Referral Center for Rare Systemic Autoimmune Diseases, Cochin Hospital, Paris, France
Background/Purpose: Eosinophilic granulomatosis with polyangiitis (EGPA) is an ANCA-associated vasculitides characterized by asthma, blood and tissue eosinophilia and systemic manifestations. Glucocorticosteroids (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: 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: Thirty-four patients were included, median age of 52.5 years (IQR, 45.3-57.0) and 23 were women (68%). Dupilumab was initiated for disabling ENT manifestations in 28 (82%) cases, poorly controlled asthma in 21 (62%) and/or GCs-dependency in 23 (68%). Dupilumab was associated with azathioprine in 2, methotrexate in 1 and mycophenolate in 1.
Median follow-up after dupilumab initiation was 7.7 (4.4-13.1) months. Nineteen (56%) patients reported adverse events (AE). Main AE were mild-to-moderate and included headache (n=2), injection-site reaction (n=2) and myalgia (n=2). Three AE were severe and led to dupilumab discontinuation: anaphylactic shock (n=2) and headache (n=1). Three additional patients discontinued dupilumab due to symptomatic hypereosinophilia (n=2) and exacerbation of psoriasis (n=1). Dupilumab-induced eosinophilia was reported in 17 patients (50%), with a peak eosinophil count of 1500/mm3 (1200-2900) after 13 weeks (4-13) of dupilumab. This transient hypereosinophilia remained asymptomatic in most cases. No death was reported.
Sixteen patients (47%) achieved a complete response and 16 (47%) a partial response. Median BVAS was 3 (0.5-4) at dupilumab initiation and dropped to 0 (0-0) at 6 months. Baseline prednisone dose was 10 mg/d (5-15) and decreased to 5 (0.6-5) at 6 months. Efficacy could not be assessed in two cases due to early discontinuation of dupilumab.
Finally, 6 (18%) patients presented a EGPA flare leading to dupilumab discontinuation in 4 cases, including asthma exacerbation in 3 cases, systemic vasculitis manifestations in 2 and inflammatory arthritis in one.
Conclusion: Dupilumab was associated with frequent mild-to-moderate AE, and induced-eosinophilia in half of patients, most frequently transient and asymptomatic. A clinical benefit was noted in most patients. Dupilumab could therefore constitute an alternative therapeutic option in selected patients refractory to anti-IL-5 drugs.
Disclosures: B. Molina, None; M. Urban, None; R. Padoan, GlaxoSmithKlein(GSK); P. Novikov, None; C. Taillé, None; M. Caminati, None; C. Christides, None; n. schleinitz, None; L. Moi, None; V. Cottin, Boehringer Ingelheim, Roche, Shionogi, RedX, PureTech, Celgene/BMS, AstraZeneca, XSL Behring, Sanofi, United Therapeutics, Pliant, Boehringer Ingelheim, Roche, Galapagos, Celgene/BMS, CSL Behring, Galecto, Fibrogen; b. godeau, None; L. Bouillet, None; P. Fraticelli, None; A. Knight, None; J. Schroeder, None; S. Marchand-Adam, None; H. Gil, None; E. Gelain, None; G. Emmi, GlaxoSmithKlein(GSK), Sobi, Novartis; B. Terrier, AstraZeneca, GlaxoSmithKline, Bristol-Myers Squibb(BMS), Eli Lilly, LFB, Boehinger Ingelheim, Vifor Pharma, Pfizer, Roche.
