Novel Targets for Drug Use in Eosinophilic Granulomatosis With Polyangiitis

Uzzo, Martina; Regola, Francesca; Trezzi, Barbara; Toniati, Paola; Franceschini, Franco; Sinico, Renato Alberto

doi:10.3389/fmed.2021.754434

Cited by 11 publications

(5 citation statements)

References 73 publications

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“…The use of the anti-CD20 monoclonal antibody rituximab is conditionally recommended in current guidelines to induce remission in patients with active, severe EGPA (7,40). Ongoing trials will test the potential clinical benefits of using rituximab, reslizumab and benralizumab for the treatment of EGPA (56).…”

Section: Biologics For Systemic Eosinophilic Diseases: Egpa and Hesmentioning

confidence: 99%

Expert consensus on the use of systemic glucocorticoids for managing eosinophil-related diseases

del Pozo,

Bobolea,

Rial

et al. 2024

Front. Immunol.

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Eosinophil-related diseases represent a group of pathologic conditions with highly heterogeneous clinical presentation and symptoms ranging from mild to critical. Both systemic and localized forms of disease are typically treated with glucocorticoids. The approval of novel biologic therapies targeting the interleukin-5 pathway can help reduce the use of systemic glucocorticoids (SGC) in eosinophilic diseases and reduce the risk of SGC-related adverse effects (AEs). In this article, a panel of experts from different medical specialties reviewed current evidence on the use of SGC in two systemic eosinophilic diseases: Eosinophilic Granulomatosis with PolyAngiitis (EGPA) and HyperEosinophilic Syndrome (HES); and in two single-organ (respiratory) eosinophilic diseases: Chronic RhinoSinusitis with Nasal Polyps (CRSwNP) and Severe Asthma with Eosinophil Phenotype (SA-EP), and contrasted it with their experience in clinical practice. Using nominal group technique, they reached consensus on key aspects related to the dose and tapering of SGC as well as on the initiation of biologics as SGC-sparing agents. Early treatment with biologics could help prevent AEs associated with medium and long-term use of SGC.

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Section: Biologics For Systemic Eosinophilic Diseases: Egpa and Hesmentioning

confidence: 99%

Expert consensus on the use of systemic glucocorticoids for managing eosinophil-related diseases

del Pozo,

Bobolea,

Rial

et al. 2024

Front. Immunol.

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“…A recent retrospective study showed Rituximab could be effective in treating relapses of EGPA vasculitis, with a higher remission rate in ANCA positive patients [34]. Other studies have shown Rituximab to be an effective glucocorticoid sparing agent [33], suggesting an alternative role in EGPA treatment (NCT02807103).…”

Section: Eosinophilic Granulomatosis With Polyangiitismentioning

confidence: 99%

“…Rituximab, an anti-CD20 monoclonal antibody, is approved for the induction and maintenance of granulomatosis with polyangiitis and microscopic polyangiitis. The mechanism of action is in part attributed to depletion of progenitors of ANCA producing plasma cells, in addition to targeting B-cell immune response [33]. A recent retrospective study showed Rituximab could be effective in treating relapses of EGPA vasculitis, with a higher remission rate in ANCA positive patients [34].…”

Section: Eosinophilic Granulomatosis With Polyangiitismentioning

confidence: 99%

Eosinophilic respiratory disorders and the impact of biologics

Bernstein

Wechsler

2023

Current Opinion in Pulmonary Medicine

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Purpose of reviewEosinophils are involved in combating parasitic, bacterial, viral infections as well as certain malignancies. However, they are also implicated in an array of upper and lower respiratory disease states. Through a deeper understanding of disease pathogenesis, targeted biologic therapies have revolutionized glucocorticoid sparing treatment of eosinophilic respiratory diseases. This review will focus on the impact of novel biologics on the management of asthma, eosinophilic granulomatosis with polyangiitis, allergic bronchopulmonary aspergillosis (ABPA), hypereosinophilic syndrome (HES) and chronic rhinosinusitis with nasal polyposis (CRSwNP).Recent findingsKey immunologic pathways affecting Type 2 inflammation through immunoglobulin E (IgE), interleukin (IL-4), IL-5, IL-13, and upstream alarmins such as thymic stromal lymphopoietin (TSLP), have led to novel drug developments. We explore the mechanism of action for Omalizumab, Mepolizumab, Benralizumab, Reslizumab, Dupilumab, and Tezepelumab, their respective Food and Drug Administration (FDA) indications, and biomarkers affecting treatment decisions. We also highlight investigational therapeutics that are likely to impact the future management of eosinophilic respiratory diseases.SummaryInsight into the biology of eosinophilic respiratory diseases has been critical for understanding disease pathogenesis and has contributed to the development of effective eosinophil-targeted biologic interventions.

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“…Patients with EGPA can be genetically distinguished into 2 groups; the first group characterized by HLA-DQA1 polymorphisms has positive MPO-ANCAs, whereas the second group has no association with HLA-DQA1 and is MPO-ANCA negative [ 16 , 17 ]. Although EGPA is classified as an ANCA-associated vasculitis, the percentage of patients with ANCA (mostly MPO/p-ANCA) varies among several studies and fluctuates between 30 and 60% [ 7 , 16 , 18 ]. Nevertheless, all patients, regardless of their ANCA status, have eosinophilia and allergic background.…”

Section: Introductionmentioning

confidence: 99%

The role of anti-eosinophilic therapies in eosinophilic granulomatosis with polyangiitis: a systematic review

2023

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Eosinophilic granulomatosis with polyangiitis (EGPA) is an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, mostly affecting small-sized arteries and usually occurring in patients with an allergic background. Eosinophils seem to play a significant role in the pathogenesis of the disease and, therefore, biologics targeting interleukin 5 (IL5), a cytokine tightly linked to eosinophils, have emerged as a promising therapeutic tool. A systematic review of Medline was conducted from 2007 to 2022 to search for data regarding the use of anti-IL5 therapies in patients with EGPA. Ongoing or unpublished trials were also searched in ClinicalTrials.gov and the World Health Organization trials portal. The efficacy and safety of mepolizumab, an anti-IL5 monoclonal antibody (mAb), was confirmed by a randomized controlled trial (RCT), although a significant proportion of patients did not respond to this treatment. Other studies showed that both doses of 100 mg and 300 mg of mepolizumab are almost equally effective in EGPA. Benralizumab, an anti-IL5 receptor mAb has preliminary promising results and an RCT is planned to be conducted. Apart from their clinical efficacy in EGPA, anti-IL5 therapies may have steroid-sparing properties. Anti-IL5 therapies seem to be effective and safe in patients with refractory/relapsing EGPA and can be used as a steroid-sparing treatment. Nevertheless, more research is needed to clarify the pathophysiology of the disease; this may potentially lead to the identification of biomarkers to pinpoint patients most likely to respond to anti-IL5-blockade.

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Novel Targets for Drug Use in Eosinophilic Granulomatosis With Polyangiitis

Cited by 11 publications

References 73 publications

Expert consensus on the use of systemic glucocorticoids for managing eosinophil-related diseases

Expert consensus on the use of systemic glucocorticoids for managing eosinophil-related diseases

Eosinophilic respiratory disorders and the impact of biologics

The role of anti-eosinophilic therapies in eosinophilic granulomatosis with polyangiitis: a systematic review

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