Real-World Efficacy and Safety of Biologics Targeting Type 2 Inflammation Across the Spectrum of Chronic Airway Diseases - A Prospective Observational Study in Asthma and COPD
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 538
- 试验地点
- 1
- 主要终点
- Annual rate of protocol-defined exacerbations of chronic airway disease over 12 months
研究概览
简要总结
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.
详细描述
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:
- Omalizumab (anti-IgE monoclonal antibody)
- Mepolizumab (anti-IL-5 monoclonal antibody)
- Benralizumab (anti-IL-5Rα monoclonal antibody)
- Dupilumab (anti-IL-4Rα monoclonal antibody, blocking IL-4/IL-13 signaling)
- Tezepelumab (anti-TSLP monoclonal antibody, effective in both T2-high and T2-low phenotypes)
- 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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must meet all of the following criteria:
- •1. Age ≥ 18 years;
- •Confirmed diagnosis of at least one of the following chronic airway diseases:
- •Asthma: Diagnosed according to the 2025 GINA guidelines, with typical variable respiratory symptoms (wheeze, shortness of breath, chest tightness, or cough) and objective evidence of variable expiratory airflow limitation (positive bronchodilator reversibility test, positive bronchial provocation test, average daily PEF variability >10%, improvement in lung function after ICS treatment, or significant variability in lung function between two visits).
- •Chronic Obstructive Pulmonary Disease (COPD): Diagnosed according to the 2026 GOLD guidelines, with symptoms of dyspnea, chronic cough, or sputum production, and/or history of exposure to risk factors, and post-bronchodilator FEV₁/FVC < 70%.
- •3. Meets clinical indications for biologic therapy as judged by a respiratory or allergy specialist according to current guidelines:
- •Asthma: Poor control despite optimized high-dose ICS-LABA therapy, presence of allergic or eosinophilic inflammatory biomarkers, or severe/refractory disease requiring maintenance oral corticosteroids (OCS).
- •COPD: Frequent exacerbations despite triple inhaled therapy (ICS + LABA + LAMA), with blood eosinophil count (EOS) ≥ 300/μL and chronic bronchitis phenotype.
- •4. The treating respiratory or allergy specialist has decided to initiate or switch to one of the following approved biologics targeting Type 2 inflammation, based on 2025 GINA and 2026 GOLD guidelines: omalizumab, mepolizumab, benralizumab, dupilumab, tezepelumab, or depemokimab (tezepelumab may be used in both Type 2 and non-Type 2 inflammation).
- •5. Able and willing to provide written informed consent and commit to at least 12 months of follow-up.
排除标准
- •Subjects will be excluded if they meet any of the following criteria:
- •Presence of severe or uncontrolled pulmonary or systemic diseases (e.g., active malignancy, autoimmune disease) or active infectious respiratory diseases (e.g., active pulmonary tuberculosis or infectious pneumonia);
- •Pregnant, breastfeeding, or planning pregnancy during the study period;
- •Known history of hypersensitivity or allergy to any component of the planned biologic agent;
- •Expected life expectancy less than 12 months;
- •Any other condition that, in the investigator's judgment, makes the subject unsuitable for participation (e.g., poor compliance or inability to complete follow-up).
研究组 & 干预措施
Adults with chronic airway diseases who have been treated with biologics
Patients with chronic airway diseases who have been treated with biologics targeting Type 2 inflammation and met the study's inclusion criteria
干预措施: Biologics targeting Type 2 inflammation (Drug)
Adults with chronic airway diseases who received the standard of care
Adults with chronic airway diseases who received the standard of care as recommended by relevant guidelines
干预措施: Patients with asthma and copd who received standard of care (Drug)
结局指标
主要结局
Annual rate of protocol-defined exacerbations of chronic airway disease over 12 months
时间窗: 12 months
Number of protocol-defined exacerbations per participant-year during the 12-month follow-up. An exacerbation is defined according to the disease-specific international criteria applicable to the participant's primary diagnosis: GINA 2026 for asthma; GOLD 2026 for COPD; ERS 2025 for bronchiectasis; and ERS 2024 for allergic bronchopulmonary aspergillosis (ABPA). Events are ascertained from participant report, medical records, and investigator assessment at scheduled and unscheduled visits.
次要结局
- Time to first exacerbation;(12 months)
- Frequency of severe exacerbations(12 months)
- Change from baseline in Asthma Control Test (ACT) total score at 3, 6, 9, 12 months(12 months)
- Change from baseline in Asthma Control Questionnaire-6 (ACQ-6) score at 3, 6, 9, 12 months(12 months)
- Change from baseline in COPD Assessment Test (CAT) total score at 3, 6, 9, 12 months(12 months)
- Change from baseline in modified Medical Research Council (mMRC) dyspnea scale at 3, 6, 9, 12 months(12 months)
- Change from baseline in Quality of Life-Bronchiectasis Respiratory Symptoms Score (QoL-B RSS) at 3, 6, 9, 12 months(12 months)
- Change from baseline in Bronchiectasis Impact Measure (BIM) total score at 12 months(12 months)
- Change from baseline in Bronchiectasis Symptom Visual Analog Scale (BS-VAS) score at 3, 6, 9, 12 months(12 months)
- Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score at 3, 6, 9, 12 months(12 months)
- Lung function parameters(12 months)
- Airway inflammation and immune biomarkers(12 months)
- Oral corticosteroid (OCS) sparing effect in asthma patients(12 months)
- Treatment persistence rate of the biologics(12 months)
研究者
Gao Yong-hua
Professor
Shanghai Pulmonary Hospital, Shanghai, China