Real-Life Effectiveness of Dupilumab in Patients With Mild to Moderate Bronchial Asthma Comorbid With CRSwNP

Shunsuke Minagawa; Jun Araya; Naoaki Watanabe; Shota Fujimoto; Junko Watanabe; Hiromichi Hara; Takanori Numata; Kazuyoshi Kuwano; Yoshinori Matsuwaki

Disclosures

BMC Pulm Med. 2022;22(258) 

In This Article

Abstract and Introduction

Abstract

Background: Dupilumab, an anti-IL-4α receptor antibody, is a new treatment for severe or refractory asthma. However, real-world evidence on the efficacy of dupilumab in patients with mild to moderate bronchial asthma is lacking.

Methods: We retrospectively evaluated the effects of dupilumab in 62 patients who received dupilumab for eosinophilic sinusitis comorbid with asthma at a single centre in Japan. Type 2 inflammatory markers, ACT, respiratory function tests, and forced oscillation technique (FOT) were analysed before, three months after, and one year after dupilumab administration, mainly in patients with mild to moderate asthma.

Results: FEV1, %FEV1, %FVC, treatment steps for asthma and ACT improved significantly after three months of dupilumab treatment. FeNO was markedly decreased, whereas IgE and eosinophil counts showed no significant changes. Pre- and post-treatment respiratory resistance (Rrs) and respiratory reactance (Xrs) correlated significantly with FEV1. Improvement in %FEV1 was associated with higher FeNO and higher serum IgE before dupilumab treatment.

Conclusion: Dupilumab treatment for sinusitis may improve respiratory functions, asthma symptoms, and asthma treatment reduction, even if the associated bronchial asthma is not severe.

Introduction

In the last few years, the treatment of refractory asthma has made dramatic progress, especially with the development of biological therapies targeting molecular effectors and signalling associated with type 2 airway inflammation.[1–5] Dupilumab is a fully-humanized IgG4 monoclonal antibody that binds to the IL-4 receptor alpha chain (IL-4Rα) and blocks both IL-4 and IL-13 signalling. Dupilumab has shown efficacy in multiple diseases associated with type 2 inflammation, including asthma, atopic dermatitis, and chronic sinusitis with nasal polyps(CRSwNP).[6] Several large clinical trials have shown that dupilumab reduces asthma exacerbations, improves the scores on obstructive pulmonary impairment and asthma control tests, and decreases the use of oral corticosteroids(OCS) regardless of peripheral blood eosinophil counts in patients with severe asthma.[7–9]

The upper airway, such as the nasal cavity and paranasal sinuses, and the lower airway, such as the bronchi and lungs, are anatomically connected and recognized as the "united airway".[10] The upper and lower airways are susceptible to functional interactions through hematogenous, transbronchial, and neuromodulatory communication of inflammatory mediators.[11–13] Therefore, it is likely that these two airways are prone to be inflamed simultaneously. It has been reported that 40 to 60% of patients with eosinophilic sinusitis and nasal polyps are complicated with asthma.[14,15] Tanaka et al. showed that 13 to 20% of eosinophilic sinusitis patients exhibited low FEV1/FVC (< 70%) on respiratory function tests without a previous diagnosis of asthma, indicating that asthma can be underdiagnosed in patients with CRS. In the SINUS-24 and SINUS-52 trials,[16] although the diagnosis of asthma was determined by self-report and patients with severe airflow obstruction were excluded, the asthma complication rate was 60%, further supporting the notion that the actual asthma complication rate may be much higher.[15] Recent reports have shown that nasal polyps and sinusitis treatment may improve asthma symptoms. Ahmed et al. have demonstrated that CRS patients tend to have less overt lower airway disorders, and endoscopic sinus surgery(ESS) effectively ameliorates such disorders.[17] In the pooled population of patients with CRSwNP complicated with asthma from the SINUS-24 and SINUS-52 trials, dupilumab improved forced expiratory volume in one second (FEV1) and patient-reported asthma symptoms evaluated by the Asthma Control Questionnaire (ACQ-6).[16] This study included all patients regardless of asthma severity. Since dupilumab is approved only for severe or poorly-controlled asthma, no previous reports have analysed the efficacy of dupilumab exclusively in patients with mild to moderate asthma, especially in real-life settings.

The forced oscillation technique (FOT) is a non-invasive, effort-independent method used for respiratory function testing in recent years and is expected to be beneficial, especially in children and the elderly, as it can be performed during tidal breathing.[18,19] However, it is not widely used yet, and its usefulness in asthma treatment has not been fully verified. Furthermore, no previous reports have used FOT to monitor the therapeutic effects of dupilumab in asthma patients.

The present study aims to retrospectively evaluate the real-life effects of dupilumab on comorbid mild to moderate asthma in patients treated with dupilumab for CRSwNP in terms of the changes in type-2 inflammatory markers, ACT, respiratory function tests, and forced oscillation technique (FOT).

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