The relationship between Feno and effectiveness of mepolizumab and benralizumab in severe eosinophilic asthma

Hearn, AP; Kavanagh, Joanne; d’Ancona, G; Roxas, C; Green, Linda; Thomson, Louise; Fernandes, Mariana; Kent, Brian D.; Dhariwal, Jaideep; Nanzer, Alexanda M.; Jackson, David J.

doi:10.1016/j.jaip.2021.01.008

Cited by 43 publications

(40 citation statements)

References 9 publications

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“…In contrast, FeNO level was derived from the IL-4/IL-13/STAT-6 signaling pathway via the upregulation of inducible nitric oxide synthase. 27,28 Interestingly, benralizumab decreases FeNO levels in asthma patients with high FeNO levels, 29 and our results are consistent with this. In addition to the original target of the IL-5 pathway, benralizumab substantially suppresses counts of basophil and group 2 innate lymphoid cells, 30,31 which are a major source of IL-4 and IL-13.…”

supporting

confidence: 89%

Feasibility of Discontinuing Biologics in Severe Asthma: An Algorithmic Approach

Hamada¹,

Oishi²,

Murata³

et al. 2021

JAA

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In severe asthma with type 2 (T2) inflammation, biologics targeting key mediators of T2 inflammation, including interleukin (IL)-5, IL-4/IL-13, and immunoglobulin (Ig)E, remarkably improve the management of severe asthma, providing new insights into the clinical course of asthma such as disease modification and broad modulation of T2 inflammation. Once severe asthma has become a "controllable" condition, the question of discontinuation of biologics arises due to cost and side effects. The studies on discontinuing biologics in asthma demonstrate that some of patients successfully discontinue biologics, indicating that it is a feasible option in a subset of patients. Incorporating the evidence of discontinuation, we propose the criteria for the discontinuation of biologics. Our proposed criteria for the discontinuation of biologics consist of an absence of asthma symptoms (asthma control questionnaire [ACQ] score < 1.5 or asthma control test [ACT] score > 19), no asthma exacerbations, no use of oral corticosteroids, normalized spirometry (forced exhaled volume in 1 second [FEV 1 ] ≥ 80%), suppressed T2 inflammation (blood eosinophil counts < 300 μL and fractional exhaled nitric oxide [FeNO] < 50 ppb), and control of asthma comorbidities. Real-world evidence verified a subset of patients achieving highly wellcontrolled conditions after use of biologics, namely super-responders, who are candidates for the discontinuation of biologics. If super-responders meet all of the criteria, they are allowed to discontinue biological therapies. Our proposed algorithm may support physicians' treatment decisions for patients receiving biologics.

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supporting

confidence: 89%

Feasibility of Discontinuing Biologics in Severe Asthma: An Algorithmic Approach

Hamada¹,

Oishi²,

Murata³

et al. 2021

JAA

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“…Real-world characteristics associated with improved response include nasal polyposis, lower baseline OCS dose and lower body mass index (BMI) [ 40 ]. In the context of eosinophilic asthma, F ENO level does not appear to predict response [ 39 , 41 ].…”

Section: Mepolizumabmentioning

confidence: 99%

A pragmatic guide to choosing biologic therapies in severe asthma

Kavanagh

Hearn

Jackson

2021

Breathe

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There are now several monoclonal antibody (mAb) therapies (“biologics”) available to treat severe asthma. Omalizumab is an anti-IgE mAb and is licensed in severe allergic asthma. Current evidence suggests it may decrease exacerbations by augmenting deficient antiviral immune responses in asthma. Like all other biologics, clinical efficacy is greatest in those with elevated T2 biomarkers. Three biologics target the interleukin (IL)-5–eosinophil pathway, including mepolizumab and reslizumab that target IL-5 itself, and benralizumab that targets the IL-5 receptor (IL-5R-α). These drugs all reduce the exacerbation rate in those with raised blood eosinophil counts. Mepolizumab and benralizumab have also demonstrated steroid-sparing efficacy. Reslizumab is the only biologic that is given intravenously rather than by the subcutaneous route. Dupilumab targets the IL-4 receptor and like mepolizumab and benralizumab is effective at reducing exacerbation rate as well as oral corticosteroid requirements. It is also effective for the treatment of nasal polyposis and atopic dermatitis. Tezepelumab is an anti-TSLP (thymic stromal lymphopoietin) mAb that has recently completed phase 3 trials demonstrating significant reductions in exacerbation rate even at lower T2 biomarker thresholds.Many patients with severe asthma qualify for more than one biologic. To date, there are no head-to-head trials to aid physicians in this choice. However, post-hoc analyses have identified certain clinical characteristics that are associated with superior responses to some therapies. The presence of allergic and/or eosinophilic comorbidities, such as atopic dermatitis, nasal polyposis or eosinophilic granulomatosis with polyangiitis, that may additionally benefit by the choice of biologic should also be taken into consideration, as should patient preferences which may include dosing frequency. To date, all biologics have been shown to have excellent safety profiles.

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“…FeNO primarily reflects IL13, which is released from Th2s, activated ILC2, eosinophils, basophils, mast cells and natural killer T cells [20]. Since activated eosinophils and basophils release IL13, depletion of these cells by benralizumab could reduce IL13, especially in patients with high FeNO level, as in our case [21].…”

Section: Discussionmentioning

confidence: 52%

IL13 May Play an Important Role in Developing Eosinophilic Chronic Rhinosinusitis and Eosinophilic Otitis Media with Severe Asthma

Shimizu

Hayashi

Kato

et al. 2021

IJMS

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A woman in her 50s was a super responder to benralizumab administered for the treatment of severe bronchial asthma (BA) with eosinophilic chronic rhinosinusitis with nasal polyp (ECRS) and eosinophilic otitis media (EOM). She exhibited the gradual exacerbation of ECRS/EOM despite good control of BA approximately 1 year after benralizumab initiation. Therefore, the treatment was switched to dupilumab, and the condition of the paranasal sinuses and middle ear greatly improved with the best control of her asthma. The patient reported that her physical condition was the best of her life. However, she developed a pulmonary opacity on chest computed tomography after 6 months. Histological examination of the lung parenchyma and cell differentiation of the bronchoalveolar lavage fluid indicated atypical chronic eosinophilic pneumonia, and treatment was switched to mepolizumab. Similarly to the period of benralizumab treatment, exacerbation of ECRS/EOM reduced her quality of life approximately 10 months after the administration of mepolizumab. Dupilumab was again introduced as a replacement for mepolizumab. The clinical course and consideration of the interaction between inflammatory cells led us to speculate that interleukin-13 could play a key role in the development of ECRS/EOM with severe BA.

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The relationship between Feno and effectiveness of mepolizumab and benralizumab in severe eosinophilic asthma

Cited by 43 publications

References 9 publications

Feasibility of Discontinuing Biologics in Severe Asthma: An Algorithmic Approach

Feasibility of Discontinuing Biologics in Severe Asthma: An Algorithmic Approach

A pragmatic guide to choosing biologic therapies in severe asthma

IL13 May Play an Important Role in Developing Eosinophilic Chronic Rhinosinusitis and Eosinophilic Otitis Media with Severe Asthma

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