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  • Sequential rituximab and mepolizumab in eosinophilic granulomatosis with polyangiitis (EGPA): a European multicentre observational study

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Letter
Sequential rituximab and mepolizumab in eosinophilic granulomatosis with polyangiitis (EGPA): a European multicentre observational study
  1. Alessandra Bettiol1,
  2. Maria Letizia Urban1,
  3. Federica Bello1,
  4. Davide Fiori1,
  5. Irene Mattioli1,
  6. Giuseppe Lopalco2,
  7. Florenzo Iannone2,
  8. Allyson Egan3,
  9. Lorenzo Dagna4,5,
  10. Marco Caminati6,
  11. Simone Negrini7,
  12. Elena Bargagli8,
  13. Marco Folci9,
  14. Franco Franceschini10,
  15. Roberto Padoan11,
  16. Oliver Flossmann12,
  17. Roser Solans13,
  18. Jan Schroeder14,
  19. Marc André15,
  20. Laura Moi16,
  21. Paola Parronchi1,
  22. Dario Roccatello17,
  23. Savino Sciascia17,
  24. David Jayne3,
  25. Domenico Prisco1,
  26. Augusto Vaglio18,
  27. Giacomo Emmi1
  28. on behalf of the European EGPA Study Group
    1. 1 Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
    2. 2 Department of Emergency and Organ Transplantation, Rheumatology Unit, University of Bari, Bari, Italy
    3. 3 Department of Medicine, University of Cambridge, Cambridge, Cambridgeshire, UK
    4. 4 Vita-Salute San Raffaele University, Milano, Italy
    5. 5 Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele, Milano, Italy
    6. 6 Department of Medicine, Asthma, Allergy and Clinical Immunology Section, University of Verona, Verona, Veneto, Italy
    7. 7 Department of Internal Medicine, Gastroenterology Unit, University of Genoa, Genoa, Italy
    8. 8 Medical Sciences Surgery and Neurosciences, University of Siena, Siena, Italy
    9. 9 Humanitas Clinical and Research Center, IRCCS Humanitas Research Hospital and Humanitas University, IRCCS Humanitas Research Hospital, Rozzano, Lombardia, Italy
    10. 10 Rheumatology and Clinical Immunology, Spedali Civili and University of Brescia, Brescia, Italy
    11. 11 Division of Rheumatology, Department of Medicine DIMED, University of Padua, Padua, Italy
    12. 12 Department of Nephrology, Royal Berkshire Hospital Reading, Reading, UK
    13. 13 Internal Medicine, Hospital Vall Hebron, Barcelona, Barcelona, Spain
    14. 14 Unit of Allergology and Immunology, Niguarda Hospital, Milan, Italy
    15. 15 Internal Medicine, G. Montpied Hospital, Clermont-Ferrand, France
    16. 16 Divion of Immunology and Allergy - Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Vaud, Switzerland
    17. 17 University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK-net, ERN-Reconnect and RITA-ERN Member) with Nephrology and Dialysis Unit and Center of Immuno-Rheumatology and Rare Diseases (CMID), and Department of Clinical and Biological Sciences of the University of Turin, San Giovanni Bosco Hub Hospital and University of Turin, Turin, Italy
    18. 18 Department of Biomedical, Experimental and Clinical Sciences "Mario Serio", and Nephrology and Dialysis Unit, University of Florence and Meyer Children's Hospital, Florence, Italy
    1. Correspondence to Dr Giacomo Emmi, Department of Experimental and Clinical Medicine, University of Florence, 50134 Firenze, Italy; giacomo.emmi{at}unifi.it

    https://doi.org/10.1136/ard-2022-222776

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      Eosinophilic granulomatosis with polyangiitis (EGPA) is an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis characterised by eosinophilic (eg, respiratory involvement, cardiomyopathy, gastroenteritis) and vasculitic manifestations (eg, neuropathy, glomerulonephritis).1

      Rituximab is an established treatment in granulomatosis with polyangiitis and microscopic polyangiitis, and growing evidence indicates that it seems effective also in EGPA, mainly to induce and maintain remission of vasculitic involvement.2 3 However, its efficacy on respiratory manifestations seems limited. Conversely, the anti-IL5 mepolizumab, recently licensed for relapsing-refractory EGPA, is effective on respiratory manifestations, although it may also partially control systemic ones.3–5

      Based on the idea that combining treatments with complementary mechanisms of action might induce and maintain remission of both disease components,6 7 we investigated the efficacy and safety of a regimen based on sequential rituximab and mepolizumab for the control of EGPA.

      This multicentre, European, retrospective study included patients meeting the American College of Rheumatology classification criteria for EGPA or the eligibility criteria proposed in the MIRRA trial.1 Only patients who received therapy with rituximab (any dosage), and subsequent treatment with mepolizumab (100–300 mg/4 weeks) within 12 months from last rituximab administration, without other induction/maintenance therapies in the meanwhile, were included.

      Treatment efficacy was assessed considering disease activity (by the Birmingham Vasculitis Activity Score, BVAS), eosinophil count and glucocorticoid dose.1 Asthma attacks and adverse events (AEs) were also assessed.

      The study received ethical approval (University of Florence IRB; ref.16821_OSS); as this …

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      Footnotes

      • DP, AV and GE are joint senior authors.

      • Handling editor Josef S Smolen

      • AB and MLU contributed equally.

      • Collaborators The manuscript is submitted on behalf on the European EGPA Study Group. Collaborators (in alphabetical order): Paolo Cameli (University of Siena, Siena, Italy), Fabrizio Conti (Sapienza University, Rome, Italy), Filippo Fagni (University of Florence, Florence, Italy and University Hospital Erlangen, Erlangen, Germany), Laura Losappio (Niguarda Hospital, Milan, Italy), Danilo Malandrino (University of Florence, Florence, Italy), Matteo Mazzetti (Careggi University Hospital, Florence, Italy), Ruggero Mazzotta (University of Florence, Florence, Italy), Luca Moroni (IRCCS Ospedale San Raffaele, Milan, and Vita-Salute San Raffaele University – Milan, Italy), Adalgisa Palermo (University of Florence, Florence, Italy), Camillo Ribi (University of Lausanne, Lausanne, Switzerland), Franco Schiavon (University of Padua, Padua, Italy), Elena Silvestri (University of Florence, Florence, Italy), Benjamin Terrier (Hôpital Cochin and Université de Paris, Paris, France), Paola Toniati (ASST Spedali Civili, Brescia, Italy)

      • Contributors All people who contributed to this work are listed as coauthors or collaborators.

      • 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 GE received consultation honoraria from GSK outside the current work. LD received consultation honoraria from GSK outside the current work. DJ’s disclosures of commercial conflicts are as follows: AstraZeneca, Aurinia, BMS, Boehringer-Ingelheim, Chemocentryx, Chugai, CSL, GSK, Infla-RX, Janssen, Novartis, Roche/Genentech, Takeda and Vifor. LM received consultation honoraria from GSK outside the current work. PP received consultation honoraria from GSK, and Novartisand LEOPharma. Professor Camillo Ribi received consultation honoraria from GSK outside the current work. JS received Advisory Board fees from AstraZeneca and GSK. AV received consultation honoraria from GSK outside the current work. All other authors and collaborators declare no conflicts of interest.

      • 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.