Combined Anti-IL-5/IL-5R and Dupilumab Therapy in Eosinophilic Granulomatosis with Polyangiitis: A European Retrospective Study

Miriam Guerini¹, Pavel Novikov², Roberto Padoan³, Georgina Espigol-Frigole⁴, Jan Willem Cohen Tervaert⁵, Vincent Grobost⁶, Laurent Guilleminault⁷, Jan Walter Schroeder⁸, Bernhard Hellmich⁹, Joana Martins-Martinho¹⁰, Camillo Ribi¹¹, Mathieu Groh¹² and Benjamin Terrier¹³, ¹IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy, ²Sechenov University, Moscow, Russia, ³University of Padova, Padova, Italy, ⁴Hospital Clínic de Barcelona, Barcelona, Spain, ⁵University of Alberta, Edmonton, AB, Canada, ⁶Internal medicine, CHU Clermont Ferrand Estaing, Clermont Ferrand, France, ⁷CHU Toulouse, Toulouse University, Toulouse, France, ⁸ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy, ⁹Klinik für Innere Medizin, Rheumatologie und Immunologie, medius Klinik Kirchheim, Kirchheim unter Teck, Germany, ¹⁰ULS Santa Maria, Lisbon, Portugal, ¹¹Lausanne University Hospital / University of Lausanne, Lausanne, Switzerland, ¹²Hôpital Foch, Suresnes, France, ¹³Cochin Hospital, Paris, France

Meeting: ACR Convergence 2025

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

Session Information

Date: Monday, October 27, 2025

Title: (1592–1611) Vasculitis – ANCA-Associated Poster II

Session Type: Poster Session B

Session Time: 10:30AM-12:30PM

Background/Purpose: Eosinophilic granulomatosis with polyangiitis (EGPA) is a small-vessel vasculitis characterized by asthma, ear, nose, and throat (ENT) symptoms, eosinophilia, and systemic involvement. Despite the use of anti-interleukin (IL)-5/IL-5R therapies, asthma or primarily ENT symptoms may persist. Dupilumab (anti-IL-4Rα) is approved for severe asthma and chronic rhinosinusitis but has been associated with drug-induced eosinophilia and EGPA flares. Given their complementary mechanisms, the combination of anti-IL-5/IL-5R and dupilumab may improve disease control in patients with EGPA. We report the safety and efficacy of this off-label combination in relapsing/refractory EGPA.

Methods: This European, multicenter, retrospective study included EGPA patients fulfilling 2022 ACR/EULAR classification criteria treated with anti-IL-5/IL-5R in combination with dupilumab for relapsed or refractory disease. Complete response (CR) was defined as BVAS=0 and prednisone dose ≤4 mg/day, partial response (PR) as BVAS=0 and prednisone dose >4 mg/day. Failure was defined as inability to reduce GCs ≤7.5 mg/day due to persistently active disease, vasculitis relapse, and/or worsening of asthma or ENT symptoms, and requiring treatment escalation.

Results: Sixteen patients received the combination therapy, with mepolizumab or benralizumab in 8 cases each. Twelve patients (75%) received the addition of dupilumab to ongoing anti-IL-5/IL-5R, 6 for uncontrolled ENT symptoms, 5 for both uncontrolled ENT and asthma symptoms, and 1 for uncontrolled asthma. The remaining 4 patients (25%) received the addition of anti-IL-5/IL-5R to dupilumab for drug-induced eosinophilia associated with vasculitis relapse in 3 and for uncontrolled ENT symptoms/asthma in 3.Safety analysis showed no serious adverse events, with only two patients experiencing mild-to-moderate adverse events.Thirteen patients with ≥3 months of follow-up were analyzed for efficacy (median follow-up 6 (3-12) months). At the start of combination therapy, the median prednisone dose was 5 mg/day (0-10), decreasing to 4.38 mg/day (0-6.25) at 3 months and 3.75 mg/day (1.25-5) at 6 months. In patients with dupilumab-induced eosinophilia, the addition of anti-IL-5/IL-5R reduced eosinophil counts from 1600/μL (1082-4000) to 170/μL (90-465) at 3 months and remained 170/μL (165-175) at 6 months. No eosinophilia occurred when dupilumab was added to anti-IL-5/IL-5R.At 3 months, 4/13 (31%) and 1/13 (8%) achieved CR and PR, respectively, while 3/13 (23%) had treatment failure. At 6 months (data available for 11 patients), 5/11 (45%) and 3/11 (27%) achieved CR and PR, respectively, and at 9 months, CR was achieved in all patients with available follow-up, except for the 3 patients with initial treatment failure.

Conclusion: The combination of anti-IL-5/IL-5R and dupilumab in this small case series was safe and appeared to be an effective option in EGPA patients with uncontrolled ENT manifestations while on anti-IL-5/IL-5R or in patients with dupilumab-induced hypereosinophilia and EGPA manifestations, with optimal response requiring at least 6 months of treatment.

Disclosures: M. Guerini: None; P. Novikov: None; R. Padoan: None; G. Espigol-Frigole: None; J. Cohen Tervaert: AbbVie/Abbott, 6, GlaxoSmithKlein(GSK), 6, Hoffmann-La Roche, 6, IDMC InflaRx, 12, Chair, Mallinckrodt Pharmaceuticals, 2, Medexus, 6, Merck/MSD, 2, Novartis, 2, Pfizer, 6, Sanofi, 6; V. Grobost: None; L. Guilleminault: None; J. Schroeder: None; B. Hellmich: CSL Vifor, 2, 6; J. Martins-Martinho: None; C. Ribi: None; M. Groh: None; B. Terrier: Amgen, 1, AstraZeneca, 1, 2, GlaxoSmithKlein(GSK), 1, 2, Novartis, 1, 2, Roche, 5, Vifor Pharma, 2.

To cite this abstract in AMA style:

Guerini M, Novikov P, Padoan R, Espigol-Frigole G, Cohen Tervaert J, Grobost V, Guilleminault L, Schroeder J, Hellmich B, Martins-Martinho J, Ribi C, Groh M, Terrier B. Combined Anti-IL-5/IL-5R and Dupilumab Therapy in Eosinophilic Granulomatosis with Polyangiitis: A European Retrospective Study [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/combined-anti-il-5-il-5r-and-dupilumab-therapy-in-eosinophilic-granulomatosis-with-polyangiitis-a-european-retrospective-study/. Accessed .

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