Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma

Menzies‐Gow, Andrew; Corren, Jonathan; Bourdin, Arnaud; Chupp, Geoffrey; Israel, Elliot; Wechsler, Michael E.; Brightling, Christopher E.; Griffiths, José-Marie; Hellqvist, Åsa; Bowen, Karin; Kaur, Primal; Almqvist, Gun; Ponnarambil, Sandhia; Colice, Gene

doi:10.1056/nejmoa2034975

Cited by 599 publications

(549 citation statements)

References 27 publications

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“…With the presence of tezepelumab, TLSP cannot bind to its receptor [ 74 ] hence inhibiting downstream signaling. A number of phase 2 and 3 trials have clearly shown that patients with severe uncontrolled asthma who received tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life than those who received placebo [ 75 , 76 ]. Concerning its safety profile, neither investigational tezepelumab-related anaphylactic reactions nor the detection of neutralizing antibodies were reported [ 75 , 76 ].…”

Section: Biologics Under Developmentmentioning

confidence: 99%

“…A number of phase 2 and 3 trials have clearly shown that patients with severe uncontrolled asthma who received tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life than those who received placebo [ 75 , 76 ]. Concerning its safety profile, neither investigational tezepelumab-related anaphylactic reactions nor the detection of neutralizing antibodies were reported [ 75 , 76 ]. To date, license application for tezepelumab has been accepted and granted Priority Review for the treatment of asthma from the US Food and Drug Administration, whose regulatory decision is expected during the first quarter of 2022.…”

Section: Biologics Under Developmentmentioning

confidence: 99%

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Biological therapy for severe asthma

Dragonieri

Carpagnano

2021

asthma res and pract

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Around 5–10% of the total asthmatic population suffer from severe or uncontrolled asthma, which is associated with increased mortality and hospitalization, increased health care burden and worse quality of life. In the last few years, new drugs have been launched and several asthma phenotypes according to definite biomarkers have been identified. In particular, therapy with biologics has revolutionized the management and the treatment of severe asthma, showing high therapeutic efficacy associated with significant clinical benefits. To date, four types of biologics are licensed for severe asthma, i.e. omalizumab (anti-immunoglobulin E) antibody, mepolizumab and reslizumab (anti-interleukin [IL]-5antibody), benralizumab (anti-IL-5 receptor a antibody) and dupilumab (anti-IL-4 receptor alpha antibody). The aim of this article was to review the biologic therapies currently available for the treatment of severe asthma, in order to help physicians to choose the most suitable biologic agent for their asthmatic patients.

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Section: Biologics Under Developmentmentioning

confidence: 99%

Section: Biologics Under Developmentmentioning

confidence: 99%

Biological therapy for severe asthma

Dragonieri

Carpagnano

2021

asthma res and pract

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“…Recently published data show the effectiveness of Tezepelumab, a biologic that targets upstream T2-inflammation, in patients with severe, uncontrolled asthma. 279 Tezepelumab blocks thymic stromal lymphopoietin (TSLP)-an epithelial-cell-derived alarmin central to the regulation of T2-immunity. TSLP acts on numerous immune cells inducing the production of T2-cytokines, ultimately resulting in airway eosinophilia, AHR and airway remodelling.…”

Section: Future Treatmentsmentioning

confidence: 99%

Recent Insights into the Management of Inflammation in Asthma

Rupani¹,

Fong²,

Kyyaly³

et al. 2021

JIR

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The present prevailing inflammatory paradigm in asthma is of T2-high inflammation orchestrated by key inflammatory cells like Type 2 helper lymphocytes, innate lymphoid cells group 2 and associated cytokines. Eosinophils are key components of this T2 inflammatory pathway and have become key therapeutic targets. Real-world evidence on the predominant T2-high nature of severe asthma is emerging. Various inflammatory biomarkers have been adopted in clinical practice to aid asthma characterization including airway measures such as bronchoscopic biopsy and lavage, induced sputum analysis, and fractional exhaled nitric oxide. Blood measures like eosinophil counts have also gained widespread usage and multicomponent algorithms combining different parameters are now appearing. There is also growing interest in potential future biomarkers including exhaled volatile organic compounds, micro RNAs and urinary biomarkers. Additionally, there is a growing realisation that asthma is a heterogeneous state with numerous phenotypes and associated treatable traits. These may show particular inflammatory patterns and merit-specific management approaches that could improve asthma patient outcomes. Inhaled corticosteroids (ICS) remain the mainstay of asthma management but their use earlier in the course of disease is being advocated. Recent evidence suggests potential roles for ICS in combination with long-acting beta-agonists (LABA) for as needed use in mild asthma whilst maintenance and reliever therapy regimes have gained widespread acceptance. Other anti-inflammatory strategies including ultra-fine particle ICS, leukotriene receptor antagonists and macrolide antibiotics may show efficacy in particular phenotypes too. Monoclonal antibody biologic therapies have recently entered clinical practice with significant impacts on asthma outcomes. Understanding of the efficacy and use of those agents is becoming clearer with a growing body of real-world evidence as is their potential applicability to other treatable comorbid traits. In conclusion, the evolving understanding of T2 driven inflammation alongside a treatable traits disease model is enhancing therapeutic approaches to address inflammation in asthma.

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“…For example, overproduction of TSLP in the skin is associated with atopic dermatitis, contact allergy and lupus skin lesions in humans (15). TSLP-specific antibodies are used to ameliorate disease in asthma patients (7,16,17). TSLP can initiate allergic airway inflammation in mice (18).…”

Section: Introductionmentioning

confidence: 99%

Interferon-λ Improves the Efficacy of Intranasally or Rectally Administered Influenza Subunit Vaccines by a Thymic Stromal Lymphopoietin-Dependent Mechanism

Schnepf

Ohnemus

et al. 2021

Front. Immunol.

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Previous work showed that interferon-λ (IFN-λ) can trigger the synthesis of thymic stromal lymphopoietin (TSLP) by specialized epithelial cells in the upper airways of mice, thereby improving the performance of intranasally administered influenza vaccines. Here we demonstrate that protein-only influenza vaccines containing either IFN-λ or TSLP boosted antigen-specific IgG1 and IgA responses and enhanced the resistance of mice to influenza virus challenge, irrespective of whether the vaccines were applied via the intranasal or the rectal route. TSLP receptor deficiency negatively influenced vaccine-induced antiviral immunity by impairing the migration of dendritic cells from the airways to the draining lymph nodes of immunized mice, thereby restraining follicular helper T cell and germinal center B cell responses. As previously observed during intranasal vaccination, the adjuvant effect of IFN-λ on a rectally administered influenza vaccine was no longer observed when TSLP receptor-deficient mice were used for immunization, highlighting the central role of the IFN-λ/TSLP axis for vaccine-induced antiviral immunity in the mucosa.

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Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma

Cited by 599 publications

References 27 publications

Biological therapy for severe asthma

Biological therapy for severe asthma

Recent Insights into the Management of Inflammation in Asthma

Interferon-λ Improves the Efficacy of Intranasally or Rectally Administered Influenza Subunit Vaccines by a Thymic Stromal Lymphopoietin-Dependent Mechanism

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