In patients with eosinophilic granulomatosis with polyangiitis (EGPA)—an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)—the use of biologic therapy that targets both the vasculitis and the eosinophilic-driven pathology associated with the disorder warrants exploration, according to findings published in Rheumatology International.
EGPA, which affects mainly small-sized arteries, can generate clinical manifestations in many organs and body systems, including the lungs, kidneys, and skin, and the nervous, gastrointestinal, and cardiovascular systems. Although the pathogenesis of the disease remains to be elucidated, as in many autoimmune disorders, strong evidence suggests the involvement of genetic and environmental factors.
Despite being classified as an AAV, the development of EGPA appears to be driven largely by eosinophils. Individuals with EGPA are shown to have an allergic background, with asthma and/or allergic sinusitis reported in between 96% and 100% of all patients. In fact, the respiratory system appears to be the system most impacted in patients with the condition. “Eosinophilic inflammation is one of the cardinal features of EGPA,” say the authors.
Standard therapy for patients with EGPA includes oral corticosteroids, along with such other immunosuppressive agents as cyclophosphamide, methotrexate, rituximab, mycophenolate, and azathioprine. Considering the fact that interleukin (IL)-5 is known to be the master cytokine that controls eosinophilic function, monoclonal antibodies (mAbs) that are active against IL-5 or the IL-5 receptor, including mepolizumab and benralizumab, respectively, are both promising therapeutic options for patients with relapsing/refractory EGPA.
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The researchers conducted a systematic review between 2007 and 2022 of all data on the use of anti-IL-5 treatments in individuals with EGPA. The literature search was limited to papers that had been published in the last 15 years. An electronic search on Medline was performed, along with ongoing or unpublished trials on ClinicalTrials.gov and the trial portal of the World Health Organization.
A total of 202 articles were retrieved. Following the exclusion of 13 duplicates, 189 articles were screened and 58 were ultimately selected for the analysis. Inclusion criteria were: 1) studies in the English language and 2) studies that reported data on anti-IL-5 therapies in humans with a confirmed diagnosis of EGPA.
The safety and efficacy of the mAb mepolizumab were verified in a randomized controlled trial, despite the fact that a considerable percentage of the patients who were evaluated did not exhibit a response to the treatment. Additional studies demonstrated that 100 and 300 mg doses of mepolizumab are nearly equivalent in the treatment of EGPA.
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The anti-IL-5 receptor mAb benralizumab has demonstrated promising results in patients with EGPA, with a randomized controlled trial soon to be under way. An additional benefit associated with anti-IL-5 therapies in patients with EGPA is their use as steroid-sparing treatment.
“[A]nti-eosinophilic therapies appear as attractive therapeutic options for patients with EGPA[,] with a good efficacy and safety profile,” the researchers explained. “Taking into account that vasculitis and eosinophilic-driven pathology overlap in patients with EGPA, combination treatment targeting both pathogenetic arms could also be explored in patients with severe/refractory disease,” they concluded.
Kouverianos I, Angelopoulos A, Daoussis D. The role of anti-eosinophilic therapies in eosinophilic granulomatosis with polyangiitis: a systematic review. Rheumatol Int. Published online April 21, 2023. doi:10.1007/s00296-023-05326-1