Comparative Efficacy and Safety of Tezepelumab and Other Biologics in Patients with Inadequately Controlled Asthma According to Thresholds of Type 2 Inflammatory Biomarkers: A Systematic Review and Network Meta-Analysis.

Koichi Ando,Hironori Sagara,Yosuke Fukuda,Akihiko Tanaka

doi:10.3390/cells11050819

Abstract

The anti-thymic stromal lymphopoietin antibody (tezepelumab) has therapeutical potential for inadequately controlled asthma. However, evidence comparing tezepelumab with other biologics is scarce. To address this issue, we performed a network meta-analysis to compare and rank the efficacy of five treatments (tezepelumab, dupilumab, benralizumab, mepolizumab, and placebo) in overall participants and in subgroups stratified by the thresholds of type 2 inflammatory biomarkers, including peripheral blood eosinophil count (PBEC) and fractional exhaled nitric oxide (FeNO). The primary endpoints were annualized exacerbation rate (AER) and any adverse events (AAEs). In the ranking assessment using surface under the cumulative ranking curve (SUCRA) of AER, tezepelumab ranked the highest overall and across subgroups (based on PBEC and FeNO level thresholds). A significant difference was observed between tezepelumab and dupilumab in the patient subgroup with PBEC < 150, and between tezepelumab and benralizumab in overall participants and the patient subgroup with PBEC ≥ 300 and ≥150, respectively. There was no significant difference in the incidence of AAEs in the overall participants between each pair of five treatment arms. These results provide a basis for the development of treatment strategies for asthma and may guide basic, clinical, or translational research.

Highlights

The widespread use of inhaled corticosteroids (ICS) and combination inhaled therapy, including ICS and bronchodilators containing two or three components, on a global scale have contributed significantly to the management of bronchial asthma [1]
In terms of efficacy based on the annualized exacerbation rate (AER), there was no significant difference between tezepelumab and mepolizumab for the overall participants group and for all subgroups analyzed according to peripheral blood eosinophil count (PBEC) thresholds, in the overall population and in subgroups with PBEC ≥ 300 and ≥150, the tezepelumab group showed a significantly better efficacy profile than the benralizumab group
We compared the efficacy and safety of tezepelumab and dupilumab in patients with inadequately controlled asthma according to thresholds of biomarkers of type 2 inflammation (PBEC or fractional exhaled nitric oxide (FeNO)) by an network meta-analysis (NMA)

Summary

Introduction

The widespread use of inhaled corticosteroids (ICS) and combination inhaled therapy, including ICS and bronchodilators containing two or three components, on a global scale have contributed significantly to the management of bronchial asthma [1] Even when these standard inhaled therapies are administered at maximum volume, approximately 10% of patients still fail to achieve adequate control [1]. Biologics targeting pro-inflammatory cytokines or mediators, such as IL-5, IL-4, and Immunoglobulin E (IgE), involved in type 2 inflammation have emerged as therapeutic options for patients whose asthma is uncontrolled by standard inhalation therapy [1–3]. These biologics may be effective against asthma caused by type 2 inflammation, they are not always effective for non-type 2 bronchial asthma. TSLPs are predominately secreted from airway epithelial cells in response to

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