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Targeting the interleukin-5 pathway in EGPA: evidence, uncertainties and opportunities
  1. Alvise Berti1,
  2. Fabiola Atzeni2,
  3. Lorenzo Dagna3,4,
  4. Stefano Del Giacco5,
  5. Giacomo Emmi6,
  6. Carlo Salvarani7,8,
  7. Augusto Vaglio9
  1. 1 Rheumatology Unit, Santa Chiara Hospital, APSS Trento and University of Trento, Trento, Italy
  2. 2 Rheumatology Unit, Ospedale Sacco, Milano, Italy
  3. 3 Unit of Immunology, Rheumatology, Allergy and Rare Diseases, Vita-Salute San Raffaele University, Milano, Italy
  4. 4 Department of Medicine and Clinical Immunology, San Raffaele Scientific Institute, Milano, Italy
  5. 5 Department of Experimental and Clinical Medicine, University of Cagliari, Cagliari, Italy
  6. 6 Department of Experimental and Clinical Medicine, University of Florence, Firenze, Italy
  7. 7 Unit of Rheumatology, Azienda Unità Sanitaria Locale-IRCCS, Reggio Emilia, Italy
  8. 8 Department of Surgery, Medicine, Dentistry and Morphological Sciences with interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
  9. 9 Deptartment of Biomedical, Experimental and Clinical Sciences, University of Florence, Firenze, Italy
  1. Correspondence to Dr Augusto Vaglio, University of Florence, Firenze, Italy; augusto.vaglio{at}


Only a minority of patients with eosinophilic granulomatosis with polyangiitis (EGPA) can be weaned-off glucocorticoids (GC) using conventional treatment strategies. The development of biological agents specifically inhibiting the IL-5 pathway provided the opportunity to treat EGPA by targeting one of the crucial regulators of eosinophils, reducing the GC dose required to control the disease.

The anti-IL-5 antibody mepolizumab at the dose of 300 mg/4 weeks has proven to be safe and effective in EGPA. While relapsing patients—who often experience recurrent respiratory manifestations—benefit from this treatment, data are not enough to support its use combined with GC alone in remission induction of severe active forms, or in remission maintenance without conventional immunosuppressants in patients with vasculitic manifestations. Ultimately, the profile of the best candidate for mepolizumab is still unclear.

Several real-life reports suggest that mepolizumab at the dose of 100 mg/4 weeks, approved for eosinophilic asthma/chronic rhinosinusitis with nasal polyposis (CRSwNP), effectively maintains remission of EGPA-related asthma and, to a lesser extent, CRSwNP. Preliminary data on the IL-5 pathway-inhibitors benralizumab and reslizumab in EGPA as steroid-sparing agents are also accumulating.

Overall, it remains to be proven whether targeting the IL-5 pathway could block progression of organ damage in EGPA, on top of reducing relapses and sparing GC. Other disease-related factors further complicate the understanding of the real anti-IL-5 agent efficacy, such as the lack of a clear definition of remission, of an effective tool to measure disease activity, and of well-defined treat-to-target approaches or goals of treatment.

  • Systemic vasculitis
  • Antirheumatic Agents
  • Autoimmune Diseases

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  • Handling editor Josef S Smolen

  • Contributors AB and AV reviewed the literature and drafted the manuscript. FA, LD, SDG, GE, and CS have critically reviewed the paper for important intellectual content.

  • 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 None declared.

  • 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.