Benralizumab attenuates airway eosinophilia in prednisone-dependent asthma

Sehmi, Roma; Lim, Hui Fang; Mukherjee, Manali; Huang, Chynna; Radford, Katherine; Newbold, Paul; Boulet, Louis‐Philippe; Dorscheid, Delbert R.; Martin, James G.; Nair, Parameswaran

doi:10.1016/j.jaci.2018.01.008

Cited by 89 publications

(73 citation statements)

References 9 publications

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“…This was in conjunction with a reduction in both circulating and sputum numbers of mature eosinophils and EoPs, suggesting an attenuation of local turnover of eosinophils . These changes were associated with reduction in maintenance dose of oral corticosteroid, improvement in asthma control, and increased lung function . This study suggests that blockade of IL‐5Rα + on ILC2s can interfere with IL‐5‐driven eosinophilopoietic processes .…”

Section: Introductionmentioning

confidence: 64%

“…Phase III clinical trial to assess the treatment of prednisone‐dependent severe asthmatics, with 30 mg subcutaneous benralizumab, a monoclonal antibody to IL‐5Rα. We found a significant reduction in blood IL‐5Rα + ILC2s, but not total ILC2s, in the benralizumab treatment arm compared to placebo . Additionally, there was a nonsignificant trend toward a decrease in sputum ILC2s.…”

Section: Introductionmentioning

confidence: 66%

“…Additionally, there was a nonsignificant trend toward a decrease in sputum ILC2s. This was in conjunction with a reduction in both circulating and sputum numbers of mature eosinophils and EoPs, suggesting an attenuation of local turnover of eosinophils . These changes were associated with reduction in maintenance dose of oral corticosteroid, improvement in asthma control, and increased lung function .…”

Section: Introductionmentioning

confidence: 79%

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The role of type 2 innate lymphoid cells in eosinophilic asthma

Salter

Sehmi

2019

Journal of Leukocyte Biology

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Eosinophilic asthma has conventionally been proposed to be a T helper 2 driven disease but emerging evidence supports a central role of type 2 innate lymphoid cells (ILC2s). These are non-T, non-B cells that lack antigen specificity and produce more IL-5 and IL-13 than CD4 + T lymphocytes, on a cell per cell basis, in vitro. Although it is clear that ILC2s and CD4 + T cells work in concert with each other to drive type 2 immune responses, kinetic studies in allergic asthma suggest that ILC2s may act locally within the airways to "initiate" eosinophilic responses, whereas CD4 + T cells act locally and systemically to "perpetuate" eosinophilic inflammatory responses. Importantly, ILC2s are increased within the airways of severe asthmatics, with the greatest number of IL-5 + IL-13 + ILC2s being detected in sputum from severe asthmatics with uncontrolled eosinophilia despite high-dose steroid therapy. Although the precise relationship between ILC2s and steroid sensitivity in asthma remains unclear, controlling the activation of ILC2s within the airways may provide an effective therapeutic target for eosinophilic inflammation in airways diseases. K E Y W O R D Seosinophilic asthma, eosinophilopoiesis, innate lymphoid cells NMU, neuromedin U; NMUR, neuromedin U receptor; PC 20 , concentration required to achieve a 20% decrease in FEV 1 ; PLZF, pro-myelocytic leukemia zinc finger; TOX, thymocyte selection associated HMB boxprotein; TSLP, thymic stromal lymphopoietin; TSLPR, thymic stromal lymphopoietin receptor. this review, we will discuss the role of innate lymphoid cells (ILCs) in eosinophilic asthma and the potential targets that drive persistent airway eosinophilia.

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Section: Introductionmentioning

confidence: 64%

Section: Introductionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 79%

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The role of type 2 innate lymphoid cells in eosinophilic asthma

Salter

Sehmi

2019

Journal of Leukocyte Biology

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“…Benralizumab depletes circulating eosinophils completely, likely through ADCC, although in some patients, small number circulatory cells still remained . However, the number of mucosal and/or submucosal airway eosinophils was less affected by the treatment when compared to the effect on the number of circulating cells .…”

Section: Effect Of Anti‐il‐5(r) On Eosinophil and Basophil Numbers Inmentioning

confidence: 95%

“…It is possible that this difference in the amount of bone marrow eosinophils and late progenitors in comparison with mepolizumab is caused by antibody‐dependent cell‐mediated cytotoxicity . Similarly, EoPs are also strongly attenuated in blood and sputum after treatment with benralizumab …”

Section: Effect Of Anti‐il‐5(receptor)mab's On Eosinophil Progenitorsmentioning

confidence: 99%

Immunological and hematological effects of IL‐5(Rα)‐targeted therapy: An overview

Hassani

Koenderman

2018

Allergy

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IL‐5 is an important cytokine for priming and survival of mature eosinophils and for proliferation and maturation of their progenitors. Hence, IL‐5(Rα) targeting will be increasingly used in diseases where eosinophils are the key immune effector cells such as eosinophilic asthma (EA), hypereosinophilic syndrome (HES), eosinophilic esophagitis (EE), and eosinophilic granulomatosis with polyangiitis (EGPA). Therefore, several neutralizing monoclonal antibodies directed against IL‐5 (mepolizumab and reslizumab) and its receptor IL‐5Rα (benralizumab) have found or will find their way to the clinic. While the clinical effect of these drugs has been extensively investigated and reviewed, the understanding of the underlying immunological and hematological mechanisms remains less clear. This review will discuss the translational outcomes of treatment with these monoclonal antibodies in humans to shed light on the mechanisms underlying the main immunological and hematological findings from these clinical trials in humans.

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Effects of anti‐IL5 biological treatments on blood IgE levels in severe asthmatic patients: A real‐life multicentre study (BIONIGE)

Contoli

Santus

Menzella

et al. 2022

Clinical & Translational All

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Background Mepolizumab and benralizumab are clinically effective biological treatments for severe eosinophilic asthmatic patients by hampering eosinophilic inflammation. The effects of these compound on the immunoglobulin (Ig)E T2 component are virtually unknown. Objectives To evaluate the change in total IgE levels at 4 ± 2 months after initiation of the mepolizumab (primary outcome) or benralizumab. When available, the changes of blood inflammatory cell counts, lung function and asthma control test (ACT) were also assessed and correlated with changes in total IgE levels. Methods Observational, retrospective, multicentre, cohort study. Severe eosinophilic atopic asthmatic patients treated with mepolizumab or benralizumab were included in the analysis. Results Three‐month treatment (on average) with mepolizumab ( n = 104) or benralizumab ( n = 82) resulted in significantly higher reduction of blood eosinophil and basophil levels in patients treated with benralizumab compared to mepolizumab. Mepolizumab did not significantly modified the levels of blood total IgE during the study period, whereas benralizumab significantly reduced (−35%, p < 0.001) total blood IgE levels. In patients treated with benralizumab the reduction of blood total Ig‐E levels correlated with the reduction of blood basophils (but not eosinophils) and weakly with the improvement of asthma control. Conclusion Benralizumab but not mepolizumab, treatment led to a significant reduction of circulating IgE level. The study provides different and specific mechanisms of action for anti‐IL5‐pathway treatments.

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Benralizumab attenuates airway eosinophilia in prednisone-dependent asthma

Cited by 89 publications

References 9 publications

The role of type 2 innate lymphoid cells in eosinophilic asthma

The role of type 2 innate lymphoid cells in eosinophilic asthma

Immunological and hematological effects of IL‐5(Rα)‐targeted therapy: An overview

Effects of anti‐IL5 biological treatments on blood IgE levels in severe asthmatic patients: A real‐life multicentre study (BIONIGE)

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