Tezepelumab in Adults with Uncontrolled Asthma

Corren, Jonathan; Parnes, Jane R.; Liang-wei, Wang; Mo, May; Roseti, Stephanie L.; Griffiths, José-Marie; Merwe, René van der

doi:10.1056/nejmoa1704064

Cited by 722 publications

(660 citation statements)

References 38 publications

Supporting

Mentioning

624

Contrasting

Unclassified

Order By: Relevance

“…Targeting these innate inflammation-amplifying loops while leaving bacterial sensing intact is an exciting challenge to tackle in future drug development approaches. Examples for current pharmacotherapeutic strategies targeting innate immune components in the respiratory space include: (1) monoclonal antibodies against innate immune cytokines (such as thymic stromal lymphopoietin [158, 159] or IL-33/ST2), (2) small molecule inhibitors targeting innate immune pathways or innate immune cell recruitment (such as CXCR2 antagonists [160–162] to dampen neutrophil recruitment), and (3) even newer technologies such as siRNA knockdown, microRNA, mRNA supplementation, or CRISPR/Cas9. A common challenge for these different therapeutic modalities is delivery into the lower airways, crossing the mucus barrier, and efficient uptake by pulmonary target cells.…”

Section: Summary and Translational Implicationsmentioning

confidence: 99%

Innate Immunity of the Lung: From Basic Mechanisms to Translational Medicine

et al. 2018

View full text Add to dashboard Cite

The respiratory tract is faced daily with 10,000 L of inhaled air. While the majority of air contains harmless environmental components, the pulmonary immune system also has to cope with harmful microbial or sterile threats and react rapidly to protect the host at this intimate barrier zone. The airways are endowed with a broad armamentarium of cellular and humoral host defense mechanisms, most of which belong to the innate arm of the immune system. The complex interplay between resident and infiltrating immune cells and secreted innate immune proteins shapes the outcome of host-pathogen, host-allergen, and host-particle interactions within the mucosal airway compartment. Here, we summarize and discuss recent findings on pulmonary innate immunity and highlight key pathways relevant for biomarker and therapeutic targeting strategies for acute and chronic diseases of the respiratory tract.

show abstract

Section: Summary and Translational Implicationsmentioning

confidence: 99%

Innate Immunity of the Lung: From Basic Mechanisms to Translational Medicine

et al. 2018

View full text Add to dashboard Cite

show abstract

“…A more recent double‐blind placebo controlled study of add‐on therapy in patients with persistent/severe asthma despite usage of high dose CCS/LABA demonstrated decreased severe exacerbations and increased FEV1 in all populations regardless of blood eosinophil counts . Finally, a mAb targeting TSLP (tezepelumab) significantly reduced exacerbations compared to placebo in patients with moderate to severe asthma that remained uncontrolled by CCS/LABA independent of blood eosinophil counts …”

Section: Asthma: Historical Perspective and Recent Advancesmentioning

confidence: 99%

Modeling asthma: Pitfalls, promises, and the road ahead

Rosenberg

Druey

2018

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Asthma is a chronic, heterogeneous, and recurring inflammatory disease of the lower airways, with exacerbations that feature airway inflammation and bronchial hyperresponsiveness. Asthma has been modeled extensively via disease induction in both wild-type and genetically manipulated laboratory mice (Mus musculus). Antigen sensitization and challenge strategies have reproduced numerous important features of airway inflammation characteristic of human asthma, notably the critical roles of type 2 T helper cell cytokines. Recent models of disease induction have advanced to include physiologic aeroallergens with prolonged respiratory challenge without systemic sensitization; others incorporate tobacco, respiratory viruses, or bacteria as exacerbants. Nonetheless, differences in lung size, structure, and physiologic responses limit the degree to which airway dynamics measured in mice can be compared to human subjects. Other rodent allergic airways models, including those featuring the guinea pig (Cavia porcellus) might be considered for lung function studies. Finally, domestic cats (Feline catus) and horses (Equus caballus) develop spontaneous obstructive airway disorders with clinical and pathologic features that parallel human asthma. Information on pathogenesis and treatment of these disorders is an important resource.

show abstract

“…Finally, a number of agents that target pathways important in eosinophilic inflammation, rather than eosinophils themselves, are being studied or have been approved for a variety of common disorders where eosinophils may play a role. These include anti‐IL‐13 (lebrikizumab, tralokinumab, RCP4046), anti‐IL‐4Rα (dupilumab), anti‐TSLP (tezepelumab), and anti‐IL‐31 (nemolizumab), various of which have demonstrated efficacy in eosinophilic asthma, atopic dermatitis (NCT02525094), nasal polyposis, and EoE (NCT02379052).…”

Section: Resultsmentioning

confidence: 99%

Revisiting the NIH Taskforce on the Research needs of Eosinophil-Associated Diseases (RE-TREAD)

Khoury

Akuthota

Ackerman

et al. 2018

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Eosinophil-associated diseases (EADs) are rare, heterogeneous disorders characterized by the presence of eosinophils in tissues and/or peripheral blood resulting in immunopathology. The heterogeneity of tissue involvement, lack of sufficient animal models, technical challenges in working with eosinophils, and lack of standardized histopathologic approaches have hampered progress in basic research. Additionally, clinical trials and drug development for rare EADs are limited by the lack of primary and surrogate endpoints, biomarkers, and validated patient-reported outcomes. Researchers with expertise in eosinophil biology and eosinophil-related diseases reviewed the state of current eosinophil research, resources, progress, and unmet needs in the field since the 2012 meeting of the NIH Taskforce on the Research of Eosinophil-Associated Diseases (TREAD). RE-TREAD focused on gaps in basic science, translational, and clinical research on eosinophils and eosinophil-related pathogenesis. Improved recapitulation of human eosinophil biology and pathogenesis in murine models was felt to be of importance. Characterization of eosinophil phenotypes, the role of eosinophil subsets in tissues, identification of biomarkers of eosinophil activation and tissue load, and a better understanding of the role of eosinophils in human disease were prioritized. Finally, an unmet need for tools for use in clinical trials was emphasized. Histopathologic scoring, patient- and clinician-reported outcomes, and appropriate coding were deemed of paramount importance for research collaborations, drug development, and approval by regulatory agencies. Further exploration of the eosinophil genome, epigenome, and proteome was also encouraged. Although progress has been made since 2012, unmet needs in eosinophil research remain a priority.

show abstract

Tezepelumab in Adults with Uncontrolled Asthma

Cited by 722 publications

References 38 publications

Innate Immunity of the Lung: From Basic Mechanisms to Translational Medicine

Innate Immunity of the Lung: From Basic Mechanisms to Translational Medicine

Modeling asthma: Pitfalls, promises, and the road ahead

Revisiting the NIH Taskforce on the Research needs of Eosinophil-Associated Diseases (RE-TREAD)

Contact Info

Product

Resources

About