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

Corren, Jonathan; Ambrose, Christopher S.; Sałapa, Kinga; Roseti, Stephanie L.; Griffiths, José-Marie; Parnes, Jane R.; Colice, Gene

doi:10.1016/j.jaip.2021.07.045

Cited by 35 publications

(66 citation statements)

References 34 publications

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“…The efficacy of tezepelumab in severe uncontrolled asthma patients has be reported in terms of improvements in reductions in exacerbation rates, healthcare utilization, spirometric indices, asthma control, and quality-of-life irrespective of patients’ blood eosinophil counts. 27 , 40 , 41 , 43 – 45 The improvements in asthma clinical outcomes observed in previous studies with tezepelumab are probably driven, at least in part, by reductions in eosinophilic airway inflammation, as shown here by reduced airway eosinophil counts regardless of baseline blood eosinophil count. 40 No reduction of neutrophils, CD3+, CD4+ lymphocytes, and subtypes of mast cells was noted in the bronchial submucosa of treated patients.…”

Section: Expert Opinionmentioning

confidence: 62%

“… 26 Pham et al 43 have reported that compared to baseline serum Il-5 and IL-13 levels, treatment with tezepelumab resulted in normalization of the levels of both T2 cytokines. In further post hoc evaluations it has been suggested that there is potential clinical efficacy and short-term tolerability of tezepelumab in patients with uncontrolled moderate-to-severe asthma with associated seasonal 44 or perennial atopy, 45 or nasal polyposis. 46 …”

Section: Mechanism Of Action Pharmaco-kinetics and -Dynamicsmentioning

confidence: 99%

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Dupilumab and tezepelumab in severe refractory asthma: new opportunities

Ragnoli

Morjaria

Pignatti

et al. 2022

Therapeutic Advances in Chronic Disease

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Bronchial asthma is a chronic inflammatory condition with increasing prevalence worldwide that may present as heterogeneous phenotypes defined by the T2-mediated pattern of airway inflammation T2-high and T2-low asthma. Severe refractory asthma includes a subset of asthmatic patients who fail to control their disease despite maximal therapy and represent a group of patients needing marked resource utilization and hence may be eligible to add-on biological therapies. Among the new biologics, we focused our attention on two monoclonal antibodies: dupilumab, exerting a dual blockade of cytokine (interleukin (IL)-4 and IL-13) signaling; and tezepelumab, acting at a higher level preventing the binding of thymic stromal lymphopoietin (TSLP) to its receptor, thus blocking TSLP, IL-25, and IL-33 signaling, hence modulating airway T2 immune responses. With their different mechanisms of action, these two biologics represent important options to provide an enhanced personalized treatment regimen. Several clinical trials have been conducted testing the efficacy and safety of dupilumab in severe refractory asthmatic patients showing improvements in lung function, asthma control, and reducing exacerbations. Similar results were reported with tezepelumab that, differently from dupilumab, acts irrespectively on eosinophilic or non-eosinophilic phenotype. In this review, we provide an overview of the most important highlights regarding dupilumab and tezepelumab characteristics and mechanism of action with a critical review of the principal results of clinical (Phase II and III) studies concluded and those still in progress.

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Section: Expert Opinionmentioning

confidence: 62%

Section: Mechanism Of Action Pharmaco-kinetics and -Dynamicsmentioning

confidence: 99%

Dupilumab and tezepelumab in severe refractory asthma: new opportunities

Ragnoli

Morjaria

Pignatti

et al. 2022

Therapeutic Advances in Chronic Disease

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“…While in the omalizumab-ineligible US or EU populations, the same tezepelumab dose reduced the AAER by 63% and 69%, respectively. 43 Similarly, in NAVIGATOR, tezepelumab reduced the AAER over 52 weeks by 59% and 67% among patients eligible for omalizumab according to US and EU prescribing information, respectively, whereas in omalizumab-ineligible patients, tezepelumab reduced the AAER by 54% and 48%, respectively. 44 , 45 These findings concur with the observations that tezepelumab therapy reduces AAER regardless of patient baseline IgE level.…”

Section: Introductionmentioning

confidence: 98%

“…In PATHWAY, treatment with tezepelumab 210 mg Q4W resulted in AAER reductions of 78% and 67%, vs placebo, in patients with allergic (n = 71) and non-allergic asthma (n = 57), respectively. 43 In NAVIGATOR, tezepelumab reduced the AAER over 52 weeks by 58% and 51%, vs placebo, in patients positive (n=339) vs negative (n=184), respectively, for perennial allergen. 41 In PATHWAY, tezepelumab 210 mg Q4W treatment was found to reduce the AAER, relative to placebo, by 82% and 77% among patients eligible for omalizumab treatment according to US or EU prescribing information, respectively.…”

Section: Introductionmentioning

confidence: 99%

“…Analyses of PATHWAY and NAVIGATOR data have examined the effect of tezepelumab on the AAER in patients with severe, uncontrolled asthma with or without allergy to a perennial aeroallergen. 41 , 43 In both studies, allergic asthma was defined as a baseline positive signal from an IgE fluorescence enzyme immunoassay to ≥1 region-specific allergens. In PATHWAY, treatment with tezepelumab 210 mg Q4W resulted in AAER reductions of 78% and 67%, vs placebo, in patients with allergic (n = 71) and non-allergic asthma (n = 57), respectively.…”

Section: Introductionmentioning

confidence: 99%

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Targeting TSLP in Asthma

Parnes¹,

Molfino²,

Colice³

et al. 2022

JAA

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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.

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