Background <p>Biologics have demonstrated lung function improvement in clinical trials. However, real-world comparative effectiveness data from European countries are limited. This real-world study compared lung function improvements with dupilumab and other biologics across five European Union (EU) countries in patients with severe asthma (SA).</p> Methods <p>The EU-ADVANTAGE was a retrospective chart review study conducted in patients (aged ≥ 12 years) with SA who initiated a biologic (dupilumab, omalizumab, benralizumab or mepolizumab) between May 2019 and February 2022 (index date). Patients with at least one record of pre-bronchodilator (BD) or post-BD forced expiratory volume in 1s (FEV₁) available within 12-month pre- and post-index periods were analysed. Inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics between treatments. Improvements in percent predicted FEV₁ (ppFEV₁) within 12 months after biologic initiation were assessed in those with either pre- or post-BD FEV₁, using doubly robust linear regression.</p> Results <p>A total of 845 patients had pre-BD ppFEV₁ and 557 had post-BD ppFEV₁ data in both pre- and post-index periods, respectively. After IPTW, several baseline characteristics were balanced (standardised mean difference &lt; 10%), and residual confounding was accounted for using doubly robust linear regression. Based on regression analysis, dupilumab-treated patients achieved a greater improvement in pre-BD ppFEV₁ than those treated with omalizumab (Δ5.25%; 95% confidence interval [CI], 3.02–7.49; <i>p</i> &lt; 0.0001), benralizumab (Δ3.23%; 95% CI, 0.03–6.43; <i>p</i> = 0.048), or mepolizumab (Δ3.29%; 95% CI, 0.33–6.24; <i>p</i> = 0.029) within 12 months. Similar differences were observed in post-BD ppFEV₁ (<i>p</i> &lt; 0.05).</p> Conclusions <p>Patients with SA initiating dupilumab had a greater lung function improvement than those initiating omalizumab, benralizumab or mepolizumab within EU clinical practice.</p>