“…15 Tezepelumab also improved lung function, asthma control, and health-related quality of life 15 and reduced health care resource utilization. 16 Furthermore, tezepelumab reduced levels of biomarkers of inflammation, including blood eosinophils, fractional exhaled nitric oxide (FENO), and total serum IgE. 15 This post hoc analysis evaluated the effect of tezepelumab in PATHWAY study participants with or without a perennial allergic phenotype, defined by sensitivity to perennial aeroallergens and by eligibility for omalizumab treatment.…”
“…15 Tezepelumab also improved lung function, asthma control, and health-related quality of life 15 and reduced health care resource utilization. 16 Furthermore, tezepelumab reduced levels of biomarkers of inflammation, including blood eosinophils, fractional exhaled nitric oxide (FENO), and total serum IgE. 15 This post hoc analysis evaluated the effect of tezepelumab in PATHWAY study participants with or without a perennial allergic phenotype, defined by sensitivity to perennial aeroallergens and by eligibility for omalizumab treatment.…”
“… Figure 4 Summary Figure: Tezepelumab Demonstrated Efficacy in a Range of Outcomes Across a Broad Population of Patients. 39 , 41 , 53 a PATHWAY included three tezepelumab doses; data from the 210-mg dose only are presented; b Nominal p value; c Score difference meets criteria for minimal clinically important difference. ns p ≥ 0.05; * p < 0.05; ** p < 0.01; *** p < 0.001 compared with placebo group.…”
Section: Discussionmentioning
confidence: 99%
“…A post hoc analysis of PATHWAY results demonstrated that tezepelumab reduced hospitalizations by 74% (RR, 0.26; 95% CI: 0.08, 0.92), 84% (RR, 0.16; 95% CI: 0.04, 0.70), and 74% (RR, 0.26; 95% CI: 0.07, 0.98) across the 70-mg-Q4W, 210-mg-Q4W, and 280-mg-Q2W dose groups, respectively, relative to placebo, over 52 weeks. 53 Tezepelumab also reduced all-cause ED visits by 56% (RR, 0.44; 95% CI: 0.14, 1.41), 84% (RR, 0.16; 95% CI: 0.04, 0.69), and 37% (RR, 0.63; 95% CI: 0.22, 1.81), relative to placebo, across the 70-mg-Q4W, 210-mg-Q4W, and 280-mg-Q2W dose groups, respectively.…”
Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine implicated in the initiation and persistence of inflammatory pathways in asthma. Released in response to a range of epithelial insults (eg, allergens, viruses, bacteria, pollutants, and smoke), TSLP initiates multiple downstream innate and adaptive immune responses involved in asthma inflammation. Inhibition of TSLP is postulated to represent a novel approach to treating the diverse phenotypes and endotypes of asthma. Tezepelumab, the TSLP inhibitor farthest along in clinical development, is a human monoclonal antibody (IgG2λ) that binds specifically to TSLP, preventing interactions with its heterodimeric receptor. Results of recently published phase 2 and 3 studies, reviewed in this article, provide evidence of the safety and efficacy of tezepelumab that builds on initial findings. Tezepelumab is safe, well tolerated, and provides clinically meaningful improvements in asthma control, including reduced incidence of exacerbations and hospitalizations in patients with severe asthma. Clinical benefits were associated with reductions in levels of a broad spectrum of cytokines (eg, interleukin [IL]-5, IL-13) and baseline biomarkers (eg, blood eosinophils, immunoglobulin [Ig]E, fractional exhaled nitric oxide [FeNO]) and were observed across a range of severe asthma phenotypes (ie, eosinophilic and non-eosinophilic). These data strengthen the notion that anti-TSLP elicits broad inhibitory effects on pathways that are key to asthma inflammation rather than on narrower inhibition of individual downstream factors. This review presents the rationale for targeting TSLP to treat asthma, as well as the clinical effects of TSLP blockade on asthma outcomes, biomarkers of disease activity, airway inflammation, lung physiology, and patient symptoms.
“…Pharmacokinetic (PK) and pharmacodynamic models predicted that subcutaneous tezepelumab 210 mg dose every 4 weeks associated with approximately 90% of the maximum drug effect on asthma exacerbation rate and FeNO [ 42 ]. A post hoc analysis of PATHWAY trial showed that tezepelumab reduced the rate of asthma exacerbations requiring hospitalizations or emergency department visits during the 52 weeks study time compared to placebo; treated patients spent fewer days in the hospital and in the intensive-care units [ 43 ]. In addition, tezepelumab reduced exacerbations and reduced type 2 inflammatory biomarkers in patients with and those without nasal polyposis compared to placebo [ 38 ].…”
Section: Targeting Thymic Stromal Lymphopoietin In Asthma: a New Fron...mentioning
Purpose of reviewOverview of epithelial cytokines, particularly thymic stromal lymphopoietin (TSLP), released by the airway epithelium and the effects of their inhibition on the outcomes of patients with asthma.
Recent findingsThe epithelial cytokines are early mediators at the top of the inflammatory cascade and are attractive therapeutic targets to prevent exacerbations and improve lung function in patients with type 2 and nontype 2 asthma.
SummaryClinical trials demonstrated that tezepelumab, an anti-TSLP monoclonal antibody, is a promising alternative treatment for asthma that is effective also in nontype 2 asthma. The PATHWAY and NAVIGATOR trials have assessed its effects in improving outcomes on broad clinically diverse populations. The identification of biomarkers will help to predict potential responders and help in asthma treatment personalization.
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