T2AIR: Real-World Efficacy and Safety of Biologics Targeting Type 2 Inflammation in Asthma and COPD

Overview

This prospective, real-world observational study (T2AIR Study) evaluates the long-term efficacy and safety of six biologics targeting Type 2 inflammation - omalizumab, mepolizumab, benralizumab, dupilumab, tezepelumab, and depemokimab - in patients with chronic airway diseases, including asthma and COPD under routine clinical practice in China. The primary objective is to determine the annualized exacerbation rate (AER) over 12 months of treatment. Secondary objectives include time to first exacerbation, frequency of severe exacerbations, improvements in symptom control and quality of life (using disease-specific questionnaires), lung function (FEV₁, FVC), airway inflammatory biomarkers (FeNO, blood eosinophils, serum IgE), oral corticosteroid (OCS) sparing effect in asthma patients, and treatment persistence. Safety outcomes will assess the incidence, types, and severity of adverse events (AEs) and serious adverse events (SAEs). Exploratory endpoints include high-resolution CT (HRCT)-based imaging markers of airway remodeling and the development of deep learning-based multimodal predictive models integrating clinical, biomarker, and radiomics data to support personalized treatment. Additionally, blood, sputum, and urine samples will be collected for translational research to explore underlying mechanisms and predictors of biologic response. This study aims to generate robust real-world evidence on the effectiveness and safety of Type 2-targeted biologics across the broad spectrum of chronic airway diseases in a diverse Chinese patient population.

Chronic airway diseases, encompassing asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous disorders characterized by chronic airway inflammation, persistent airflow limitation, and/or airway hyperresponsiveness. These conditions commonly present with chronic cough, sputum production, and dyspnea. Acute exacerbations can be life-threatening and represent a leading global cause of disability and premature mortality among chronic non-communicable diseases. Although inhaled corticosteroids (ICS) combined with long-acting bronchodilators (LABA/LAMA) form the mainstay of treatment, a substantial proportion of patients - approximately 5-10% with asthma and selected COPD patients experience severe or refractory disease. These patients suffer from recurrent exacerbations, progressive lung function decline, impaired quality of life, and serious complications associated with long-term oral corticosteroid (OCS) use, including osteoporosis and increased infection risk. Type 2 (T2-high) inflammation, driven by eosinophil activation and the IL-4/IL-5/IL-13 signaling pathways, plays a central role in the pathogenesis of most severe asthma cases and a significant subset of COPD patients. In recent years, biologics targeting key mediators of Type 2 inflammation - including IgE, IL-5/IL-5Rα, IL-4Rα, and thymic stromal lymphopoietin (TSLP) - have emerged as precision therapeutic options for patients inadequately controlled on standard therapy. The six biologics evaluated in this study are: 1. Omalizumab (anti-IgE monoclonal antibody) 2. Mepolizumab (anti-IL-5 monoclonal antibody) 3. Benralizumab (anti-IL-5Rα monoclonal antibody) 4. Dupilumab (anti-IL-4Rα monoclonal antibody, blocking IL-4/IL-13 signaling) 5. Tezepelumab (anti-TSLP monoclonal antibody, effective in both T2-high and T2-low phenotypes) 6. Depemokimab (ultra-long-acting anti-IL-5 Fc-fusion protein enabling twice-yearly dosing) Current international guidelines (GINA 2026 and GOLD 2026) recommend these Type 2-targeted biologics as add-on therapy for moderate-to-severe patients with poor control despite optimized standard care, with selection often guided by biomarkers such as blood eosinophils (EOS) and fractional exhaled nitric oxide (FeNO). While these agents have demonstrated efficacy in randomized controlled trials (RCTs) for severe asthma and eosinophilic COPD, robust real-world evidence remains limited, long-term use, diverse phenotypes, elderly patients, and those with multiple comorbidities. Moreover, data specific to Chinese populations are scarce. This prospective real-world observational study aims to address these evidence gaps.