Novel Therapeutic Option Striking Multiple Downstream Inflammatory Pathways Associated with Uncontrollable Asthma

JoAnn Filipov, Mercer University College of Pharmacy

Despite established standard of care therapies, literature suggests that patients diagnosed with moderate-to-severe asthma experience frequent exacerbations and significant lung function limitations due to uncontrolled asthma. [1] A proposed molecular mechanism in asthma is the type 2 (T2) inflammatory pathway, characterized by elevated levels of blood eosinophils, serum IgE, and fractional exhaled nitric oxide (FENO). [2] Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine central for regulation of T2 immunity.  It has been identified as a potential therapeutic target for its ability to activate various cell types, such as basophils, mast cells, innate lymphoid cells, natural killer T cells, and neutrophils, across a broad patient population. [3]

Tezepelumab is an investigational human IgG2 monoclonal antibody. It binds to TSLP to prevent TSLP-receptor interaction. [4] This mechanism prevents the release of cytokines via immune cells targeted by TSLP early in the inflammation cascade. [5] It has been suggested that tezepelumab could be an adjunct therapy for patients with a history of asthma exacerbations and uncontrolled asthma who have failed previous therapies. [6]

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