scholarly journals Benralizumab: From the Basic Mechanism of Action to the Potential Use in the Biological Therapy of Severe Eosinophilic Asthma

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Corrado Pelaia ◽  
Cecilia Calabrese ◽  
Alessandro Vatrella ◽  
Maria Teresa Busceti ◽  
Eugenio Garofalo ◽  
...  
Keyword(s):  
Biological Therapy ◽  
Airway Disease ◽  
Basic Mechanism ◽  
Lymphoid Cells ◽  
Biologic Drugs ◽  
Eosinophilic Asthma ◽  
Interleukin 5 ◽  
Severe Eosinophilic Asthma ◽  
Bronchial Inflammation ◽  
Group 2

Asthma is a very frequent chronic airway disease that includes many different clinical phenotypes and inflammatory patterns. In particular, eosinophilic bronchial inflammation is often associated with allergic as well as nonallergic asthma. The most important cytokine involved in the induction, maintenance, and amplification of airway eosinophilia in asthma is interleukin-5 (IL-5), released by both T helper 2 (Th2) lymphocytes and group 2 innate lymphoid cells (ILC2). Hence, IL-5 and its receptor are suitable targets for selective biologic drugs which can play a key role in add-on treatment of severe eosinophilic asthma refractory to corticosteroids. Within such a context, the anti-IL-5 monoclonal antibodies mepolizumab and reslizumab have been developed and approved for biological therapy of uncontrolled eosinophilic asthma. In this regard, on the basis of several successful randomized controlled trials, the anti-IL-5 receptor benralizumab has also recently obtained the approval from US Food and Drug Administration (FDA).

scholarly journals Mepolizumab in the management of severe eosinophilic asthma in adults: current evidence and practical experience

2016 ◽  
Vol 11 (1) ◽  
pp. 40-45 ◽  
Author(s):  
Gilda Varricchi ◽  
Diego Bagnasco ◽  
Matteo Ferrando ◽  
Francesca Puggioni ◽  
Giovanni Passalacqua ◽  
...  
Keyword(s):  
Practical Experience ◽  
Lymphoid Cells ◽  
Th2 Cells ◽  
Current Evidence ◽  
Blood Leukocytes ◽  
Eosinophilic Asthma ◽  
Gm Csf ◽  
Severe Eosinophilic Asthma ◽  
Nk T Cells ◽  
Group 2

Eosinophils represent approximately 1% of peripheral blood leukocytes in normal donors and their maturation and differentiation in the bone marrow are mainly regulated by interleukin (IL)-5 [Broughton et al. 2015]. IL-5, a cytokine that belongs to the β common-chain family, together with IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF), stimulates also the activation and survival of eosinophils and, to some extent, of basophils. IL-5 binds to a heterodimer receptor composed of the specific subunit IL-5Rα and a common subunit βc shared with IL-3 and GM-CSF. Human eosinophils express approximately a three-fold higher level of IL-5Rα compared with basophils. Major sources of IL-5 are T-helper 2 (Th2) cells, mast cells, CD34+ progenitor cells, invariant natural killer (NK) T-cells, group 2 innate lymphoid cells (ILC2s), and eosinophils themselves. ILC2s control not only eosinophil number but also their circadian cycling through the production of IL-5.

scholarly journals Severe eosinophilic bronchial asthma: new therapeutic options

2018 ◽  
pp. 44-52 ◽  
Author(s):  
N. M. Nenasheva
Keyword(s):  
Monoclonal Antibodies ◽  
Severe Asthma ◽  
Bronchial Asthma ◽  
Biological Agents ◽  
Therapeutic Options ◽  
Clinical Use ◽  
Eosinophilic Asthma ◽  
Interleukin 5 ◽  
Severe Eosinophilic Asthma

Eosinophilic asthma is a common phenotype of severe asthma, occurring in at least half of patients. In recent years, there have been significant changes in the approaches to the treatment of severe bronchial asthma and, above all, eosinophilic asthma. The article discusses the role of eosinophils in the pathogenesis of severe asthma, the detection of the phenotype of severe eosinophilic asthma, and modern approaches to targeting severe asthma with an eosinophilic phenotype using biological agents. A special emphasis is placed on preparations of monoclonal antibodies to interleukin-5, in particular, mepolizumab, recently approved for clinical use in our country.

scholarly journals Corticosteroid tapering with benralizumab treatment for eosinophilic asthma: PONENTE Trial

2019 ◽  
Vol 5 (3) ◽  
pp. 00009-2019 ◽  
Author(s):  
Andrew Menzies-Gow ◽  
Jonathan Corren ◽  
Elisabeth H. Bel ◽  
Jorge Maspero ◽  
Liam G. Heaney ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Asthma Control ◽  
Severe Asthma ◽  
Maintenance Phase ◽  
Phase Iii ◽  
Eosinophilic Asthma ◽  
Interleukin 5 ◽  
Severe Eosinophilic Asthma ◽  
Link Type ◽  
Related Quality

Benralizumab is an interleukin-5 receptor α-directed cytolytic monoclonal antibody approved in several countries for the add-on maintenance treatment of patients with severe eosinophilic asthma aged 12 years and older. In the 28-week Phase III ZONDA trial (ClinicalTrials.gov identifier: NCT02075255), benralizumab produced a median 75% reduction from baseline in oral corticosteroid (OCS) dosage (versus 25% for placebo) while maintaining asthma control for patients with OCS-dependent severe asthma. This manuscript presents the detailed protocol for the Phase IIIb PONENTE (ClinicalTrials.gov identifier: NCT03557307), a study that will build on the findings from ZONDA.As the largest steroid-sparing study undertaken in severe asthma, PONENTE has a faster steroid tapering schedule for prednisone dosages ≥7.5 mg·day−1 than previous studies, and it includes an evaluation of adrenal insufficiency and an algorithm to taper OCS dosage when prednisone dosage is ≤5 mg·day−1. It also has a longer maintenance phase to assess asthma control for up to 6 months after completion of OCS tapering.The two primary endpoints are whether patients achieve 100% reduction in daily OCS use and whether patients achieve 100% reduction in daily OCS or achieve OCS dosage ≤5 mg·day−1, if adrenal insufficiency prevented further reduction, both sustained over ≥4 weeks without worsening of asthma. Safety and change from baseline in health-related quality of life will also be assessed.PONENTE should provide valuable guidance for clinicians on tapering OCS dosage, including the management of adrenal insufficiency, following benralizumab initiation for the treatment of patients who are OCS-dependent with severe, uncontrolled eosinophilic asthma.

scholarly journals Responses to Biological Therapy in Severe Eosinophilic Asthma

2019 ◽  
Vol 29 (4) ◽  
pp. 335-337
Author(s):  
MJ Alvarez-Puebla ◽  
E Arroabarren ◽  
MJ Zavala ◽  
A Corcuera ◽  
A Olaguibel ◽  
...  
Keyword(s):  
Biological Therapy ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma

Human innate lymphoid cells

Blood ◽  
2014 ◽  
Vol 124 (5) ◽  
pp. 700-709 ◽  
Author(s):  
Mette D. Hazenberg ◽  
Hergen Spits
Keyword(s):  
Interferon Γ ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Interleukin 5 ◽  
Type 2 Cytokines ◽  
Lymphoid Tissue Inducer Cells ◽  
Health And Disease ◽  
Group 2 ◽  
And Function ◽  
Regulatory Functions

Innate lymphoid cells (ILCs) are lymphoid cells that do not express rearranged receptors and have important effector and regulatory functions in innate immunity and tissue remodeling. ILCs are categorized into 3 groups based on their distinct patterns of cytokine production and the requirement of particular transcription factors for their development and function. Group 1 ILCs (ILC1s) produce interferon γ and depend on Tbet, group 2 ILCs (ILC2s) produce type 2 cytokines like interleukin-5 (IL-5) and IL-13 and require GATA3, and group 3 ILCs (ILC3s) include lymphoid tissue inducer cells, produce IL-17 and/or IL-22, and are dependent on RORγt. Whereas ILCs play essential roles in the innate immune system, uncontrolled activation and proliferation of ILCs can contribute to inflammatory autoimmune diseases. In this review, we provide an overview of the characteristics of ILCs in the context of health and disease. We will focus on human ILCs but refer to mouse studies if needed to clarify aspects of ILC biology.

scholarly journals Heterogeneous Response of Airway Eosinophilia to Anti-IL-5 Biologics in Severe Asthma Patients

2022 ◽  
Vol 12 (1) ◽  
pp. 70
Author(s):  
Maruša Kopač Šokić ◽  
Matija Rijavec ◽  
Peter Korošec ◽  
Urška Bidovec-Stojkovič ◽  
Izidor Kern ◽  
...  
Keyword(s):  
Treatment Strategies ◽  
Eosinophilic Inflammation ◽  
Asthma Control Test ◽  
Sputum Induction ◽  
Immunological Parameters ◽  
Eosinophilic Asthma ◽  
Interleukin 5 ◽  
Severe Eosinophilic Asthma ◽  
Asthma Patients

Many questions concerning responders (R) and nonresponders (NR) in severe eosinophilic asthma (SEA) after blocking the IL-5 (interleukin 5) pathway are still not clear, especially regarding the early parameters of response to biologics in personalized treatment strategies. We evaluated 17 SEA patients treated with anti-IL-5 biologics (16 patients mepolizumab, one patient benralizumab) before the introduction of biologics, and at a week 16 follow-up. Clinical, cellular and immunological parameters in peripheral blood were measured in R and NR. Sputum induction with the measurement of cellular and immunological parameters was performed at 16 weeks only. There were 12 R and 5 NR to biologics. After 16 weeks, there was a significant improvement in percentages of FEV1 (p = 0.001), and asthma control test (ACT) (p = 0.001) in the R group, but not in NR. After 16 weeks, the eosinophils in induced sputum were 27.0% in NR and 4.5% in R (p = 0.05), with no difference in IL-5 concentrations (p = 0.743). Peripheral eosinophilia decreased significantly in NR (p = 0.032) and R (p = 0.002). In patients with SEA on anti-IL-5 therapy, there was a marked difference in airway eosinophilic inflammation between R and NR already at 16 weeks, after anti-IL-5 introduction.

The Role of the TL1A/DR3 Axis in the Activation of Group 2 Innate Lymphoid Cells in Subjects with Eosinophilic Asthma

2020 ◽  
Vol 202 (8) ◽  
pp. 1105-1114 ◽  
Author(s):  
Kentaro Machida ◽  
Michael Aw ◽  
Brittany M. A. Salter ◽  
Xiaotian Ju ◽  
Manali Mukherjee ◽  
...  
Keyword(s):  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Eosinophilic Asthma ◽  
Group 2

Regulatory eosinophils induce the resolution of experimental arthritis and appear in remission state of human rheumatoid arthritis

2020 ◽  
pp. annrheumdis-2020-218902 ◽  
Author(s):  
Darja Andreev ◽  
Mengdan Liu ◽  
Katerina Kachler ◽  
Mireia Llerins Perez ◽  
Philipp Kirchner ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Antibody Therapy ◽  
Chronic Arthritis ◽  
Lymphoid Cells ◽  
Human Rheumatoid Arthritis ◽  
Antibody Treatment ◽  
Eosinophilic Asthma ◽  
Interleukin 5 ◽  
Specific Subset ◽  
Before And After

ObjectivesEosinophils possess pro-inflammatory functions in asthma. However, our recent studies have suggested that innate lymphoid cells type 2 (ILC2s) and eosinophils have proresolving properties in rheumatoid arthritis (RA). Nothing is known yet about the mechanisms determining the double-edged role of eosinophils. Therefore, we investigated whether asthma, a paradigm eosinophilic disease, can elicit resolution of chronic arthritis.MethodsOvalbumin-triggered eosinophilic asthma was combined with K/BxN serum-induced arthritis, where lung and synovial eosinophil subsets were compared by single-cell RNA sequencing (scRNA-seq). To investigate the involvement of the ILC2–interleukin-5 (IL-5) axis, hydrodynamic injection (HDI) of IL-25 and IL-33 plasmids, IL-5 reporter mice and anti-IL-5 antibody treatment were used. In patients with RA, the presence of distinct eosinophil subsets was examined in peripheral blood and synovial tissue. Disease activity of patients with RA with concomitant asthma was monitored before and after mepolizumab (anti-IL-5 antibody) therapy.ResultsThe induction of eosinophilic asthma caused resolution of murine arthritis and joint tissue protection. ScRNA-seq revealed a specific subset of regulatory eosinophils (rEos) in the joints, distinct from inflammatory eosinophils in the lungs. Mechanistically, synovial rEos expanded on systemic upregulation of IL-5 released by lung ILC2s. Eosinophil depletion abolished the beneficial effect of asthma on arthritis. rEos were consistently present in the synovium of patients with RA in remission, but not in active stage. Remarkably, in patients with RA with concomitant asthma, mepolizumab treatment induced relapse of arthritis.ConclusionThese findings point to a hitherto undiscovered proresolving signature in an eosinophil subset that stimulates arthritis resolution.

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