Targeting the interleukin-5 pathway in EGPA: evidence, uncertainties and opportunities.

Abstract

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.

• Authors: Alvise Berti, Fabiola Atzeni, Lorenzo Dagna, Stefano Del Giacco, Giacomo Emmi, Carlo Salvarani, Augusto Vaglio
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 82 Issue 2 Pg. 164-168 (Feb 2023) ISSN: 1468-2060 [Electronic] England
• PMID: 36357156 (Publication Type: Journal Article)
• Copyright: © Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Interleukin-5
• Immunosuppressive Agents
• Glucocorticoids

Topics

• Humans
• Granulomatosis with Polyangiitis (drug therapy)
• Churg-Strauss Syndrome (drug therapy)
• Interleukin-5 (therapeutic use)
• Immunosuppressive Agents (therapeutic use)
• Glucocorticoids (therapeutic use)
• Asthma (drug therapy)