Comorbidities as a Personalized Target in Patients with Severe Asthma Treated with Dupilumab

<b>Background:</b> This study aimed to evaluate the clinical effectiveness of dupilumab and its impact on CRSwNP and type 2 inflammatory biomarkers in patients with severe uncontrolled asthma, with or without comorbidities, within a real-life cohort. <b>Methods:</b> This was a single-center, prospective, and observational real-life study conducted at the Severe Asthma Unit of Germans Trias i Pujol University Hospital. The objective of this study was to assess the real-world response to dupilumab treatment in patients with severe asthma, with or without nasal polyposis, bronchiectasis, obesity, or switching from another biologic drug for their asthma. <b>Results:</b> The ACT score significantly increased (13.7 vs. 20.6; <i>p</i> = 0.001), while the number of exacerbations decreased (3.1 vs. 0.7; <i>p</i> = 0.005). Patients with CRSwNP showed an increase in the ACT score (13.1 vs. 19.8; <i>p</i> = 0.011) and a decrease in the number of exacerbations (3.0 vs. 1.3; <i>p</i> = 0.217). Patients with nasal polyps showed an increase in both SNOT22 (78.3 vs. 38.3; <i>p</i> = 0.013) and global VAS (8 vs. 4.2; <i>p</i> = 0.028). Patients with bronchiectasis receiving dupilumab showed an increase in the ACT score (12.7 vs. 21.3; <i>p</i> = 0.039) and a marked decrease in the number of exacerbations (2.8 vs. 0; <i>p</i> = 0.025). Obese patients treated with dupilumab showed an improvement in the ACT score (14.1 vs. 21.3; <i>p</i> = 0.044) and a decrease in the rate of exacerbations (3.2 vs. 1.3; <i>p</i> = 0.030). Patients with rhinoconjunctivitis receiving dupilumab showed an increase in the ACT score (13.4 vs. 19.1; <i>p</i> = 0.017) and a decrease in the number of exacerbations (3.3 vs. 0.8; <i>p</i> = 0.024). <b>Conclusions:</b> Dupilumab is a highly effective treatment for severe asthma, showing significant improvements in lung function, reductions in exacerbations, and enhanced quality of life for patients with and without nasal polyps. The results of this real-life study support dupilumab as a valuable addition to the therapeutic armamentarium for asthma, particularly for those with type 2 inflammation despite the presence of comorbidities such as bronchiectasis or obesity, or for patients in whom a previous biologic treatment failed.