Effect of tezepelumab on airway inflammatory cells, remodelling, and hyperresponsiveness in patients with moderate-to-severe uncontrolled asthma (CASCADE): a double-blind, randomised, placebo-controlled, phase 2 trial

Diver, Sarah; Khalfaoui, Latifa; Emson, Claire; Wenzel, Sally E.; Menzies‐Gow, Andrew; Wechsler, Michael E.; Johnston, James; Molfino, Néstor A.; Parnes, Jane R.; Megally, Ayman; Colice, Gene

doi:10.1016/s2213-2600(21)00226-5

Cited by 177 publications

(206 citation statements)

References 26 publications

Supporting

Mentioning

168

Contrasting

Unclassified

Order By: Relevance

“…15 The efficacy of tezepelumab in both allergic and nonallergic asthma is likely due to the wide-ranging effects of blocking TSLP. Tezepelumab has been shown to reduce eosinophilic inflammation in the airway of patients with moderate to severe asthma, 30 as well as levels of cytokines such as IL-5 and IL-13, 31 elevated levels of which are characteristic of allergic asthma. 1 In addition, tezepelumab has been found to reduce airway hyperresponsiveness in these patients, 30,32 which may lead to improved clinical outcomes in both allergic and nonallergic patients.…”

Section: Discussionmentioning

confidence: 99%

“…Tezepelumab has been shown to reduce eosinophilic inflammation in the airway of patients with moderate to severe asthma, 30 as well as levels of cytokines such as IL-5 and IL-13, 31 elevated levels of which are characteristic of allergic asthma. 1 In addition, tezepelumab has been found to reduce airway hyperresponsiveness in these patients, 30,32 which may lead to improved clinical outcomes in both allergic and nonallergic patients. Blocking TSLP may also have suppressive effects on non-T2 inflammatory processes with particular relevance in nonallergic asthma.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Efficacy of Tezepelumab in Patients with Severe, Uncontrolled Asthma and Perennial Allergy

Corren

Ambrose

Sałapa

et al. 2021

The Journal of Allergy and Clinical Immunology: In Practice

Self Cite

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Efficacy of Tezepelumab in Patients with Severe, Uncontrolled Asthma and Perennial Allergy

Corren

Ambrose

Sałapa

et al. 2021

The Journal of Allergy and Clinical Immunology: In Practice

Self Cite

View full text Add to dashboard Cite

“…A mechanistic placebo-controlled study of tezepelumab, “CASCADE”, recruited patients on moderate or high dose ICS plus another controller and conducted bronchoscopies at baseline and end of treatment, along with measures of bronchial hyperresponsiveness and airway remodelling. Tezepelumab treatment resulted in a reduction in submucosal eosinophils irrespective of baseline blood eosinophils and a decrease in airway hyperresponsiveness; however, there was no effect on other inflammatory cells in the submucosa or significant improvements in the airway remodelling outcomes [ 89 ].…”

Section: Tezepelumabmentioning

confidence: 99%

A pragmatic guide to choosing biologic therapies in severe asthma

Kavanagh

Hearn

Jackson

2021

Breathe

View full text Add to dashboard Cite

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.

show abstract

“…Indeed, mucolytics (i.e., hypertonic saline and rhDNAse) are able to influence mucus hydration [ 71 , 125 ], whereas macrolides (azithromycin, erythromycin) inhibit mucus secretion and have proved to reduce exacerbations in obstructive lung diseases [ 152 , 153 , 154 ]. In the wake of monoclonal antibodies within the asthma context (anti-IL5/5R, anti-IL-4/13R, anti-TSLP) [ 155 , 156 , 157 , 158 ], some of which directly affect airway remodeling or even inhibit mucus secretion, the implementation of “basic science” methods as a point-of-care or simply to guide therapy would be of great value (COPD CaRhe— , accessed on 21 December 2021, NCT04339270). Finally, in order to better understand the complexity of mucus regulation, it is likely that a multimodal approach will enable us to progress towards what we call “tailored medicine” and may even allow for early disease detection.…”

Section: Discussionmentioning

confidence: 99%

Methods of Sputum and Mucus Assessment for Muco-Obstructive Lung Diseases in 2022: Time to “Unplug” from Our Daily Routine!

Charriot

Volpato

Petit

et al. 2022

Cells

View full text Add to dashboard Cite

Obstructive lung diseases, such as chronic obstructive pulmonary disease, asthma, or non-cystic fibrosis bronchiectasis, share some major pathophysiological features: small airway involvement, dysregulation of adaptive and innate pulmonary immune homeostasis, mucus hyperproduction, and/or hyperconcentration. Mucus regulation is particularly valuable from a therapeutic perspective given it contributes to airflow obstruction, symptom intensity, disease severity, and to some extent, disease prognosis in these diseases. It is therefore crucial to understand the mucus constitution of our patients, its behavior in a stable state and during exacerbation, and its regulatory mechanisms. These are all elements representing potential therapeutic targets, especially in the era of biologics. Here, we first briefly discuss the composition and characteristics of sputum. We focus on mucus and mucins, and then elaborate on the different sample collection procedures and how their quality is ensured. We then give an overview of the different direct analytical techniques available in both clinical routine and more experimental settings, giving their advantages and limitations. We also report on indirect mucus assessment procedures (questionnaires, high-resolution computed tomography scanning of the chest, lung function tests). Finally, we consider ways of integrating these techniques with current and future therapeutic options. Cystic fibrosis will not be discussed given its monogenic nature.

show abstract

Effect of tezepelumab on airway inflammatory cells, remodelling, and hyperresponsiveness in patients with moderate-to-severe uncontrolled asthma (CASCADE): a double-blind, randomised, placebo-controlled, phase 2 trial

Cited by 177 publications

References 26 publications

Efficacy of Tezepelumab in Patients with Severe, Uncontrolled Asthma and Perennial Allergy

Efficacy of Tezepelumab in Patients with Severe, Uncontrolled Asthma and Perennial Allergy

A pragmatic guide to choosing biologic therapies in severe asthma

Methods of Sputum and Mucus Assessment for Muco-Obstructive Lung Diseases in 2022: Time to “Unplug” from Our Daily Routine!

Contact Info

Product

Resources

About