Comparative effectiveness of omalizumab in asthma-COPD overlap vs. asthma: a retrospective cohort study

Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) represents a heterogeneous phenotype with diagnostic challenges and variable responses to biologic therapies. Omalizumab, an anti-IgE monoclonal antibody, is effective in allergic asthma but shows limited efficacy in ACO, necessitating mechanistic insights into treatment heterogeneity. This study aims to compare the 20-week omalizumab efficacy between ACO and non-ACO asthma patients and to assess how differing ACO diagnostic criteria affect Th2-inflammatory biomarker dynamics and clinical outcomes.

We retrospectively analyzed the clinical data of asthma patients who received omalizumab therapy at our hospital between March 2024 and January 2025. All enrolled patients had a documented asthma diagnosis according to the Global Initiative for Asthma (GINA) guidelines. Participants were categorized into ACO and non-ACO asthma groups based on two distinct criteria. The ACO-A group was defined by a prior diagnosis or self-reported history of COPD superimposed on asthma. The ACO-B group required a post-bronchodilator (BD) forced expiratory volume in one second to forced vital capacity ratio (post BD FEV₁/FVC) < 0.7 and a smoking history of ≥10 pack-years in addition to the asthma diagnosis. Serological, airway inflammatory, and pulmonary function biomarkers related to asthma were measured and comparatively analyzed.

A total of 74 patients were enrolled, of whom 25 were ACO-A, 49 were non-ACO-A, 11 were ACO-B, and 63 were non-ACO-B. Patients with ACO exhibited poorer baseline lung function and higher smoking exposure than those with asthma alone. While both groups showed increased asthma control test (ACT) scores, the non-ACO-A group displayed decreased fractional exhaled nitric oxide (FeNO) and eosinophil (EOS) (all p < 0.001) and increased serum total IgE, pre-BD FEV₁%predicted, post-BD FEV₁%predicted, and post-BD FEV₁/FVC (all p < 0.001). Changes in serum total IgE, FeNO, and pre-BD FEV₁%predicted (all p < 0.05) were greater in the non-ACO-A group than in the ACO-A group.

Our findings demonstrate that the Th2-high inflammatory endotype, rather than the ACO diagnostic label, is the primary predictor of omalizumab response. Prioritizing direct assessment of Th2 inflammation over the ACO definition can better guide biologic therapy.

www.medicalresearch.org.cn/, identifier MR-31-24-055473.