Real-World Effectiveness of Dupilumab in Severe Uncontrolled Asthma: Clinical Remission on Treatment, Predictors of Complete Response and Impact on Type-2 Comorbidities.

Background/

Objectives

Real-world evidence on dupilumab-induced clinical remission on treatment and on the predictors of complete response in severe uncontrolled asthma (SUA) is still limited.

Methods

We conducted a single-centre ambispective uncontrolled observational study including 152 adults with SUA who started dupilumab. Lung function, type-2 (T2) biomarkers, patient-reported outcomes, exacerbations, oral corticosteroid (OCS) use, emergency-department (ED) visits and hospitalisations were compared between baseline and last follow-up. Response was graded with FEOS and EXACTO. Independent predictors of complete response (EXACTO = 1) were explored by multivariable logistic regression.

Results

Mean age was 50 ± 12 years, 67.1% were women, baseline FEV1 was 82 ± 22% predicted, blood eosinophils were 612 ± 577 cells/µL and FeNO was 55 ± 46 ppb. After 21 ± 8 months, ACT improved from 15.7 to 23.3, ACQ-5 from 4.0 to 0.35, mini-AQLQ from 2.18 to 4.53, SNOT-22 from 52 to 16, and FEV1 by 275 ± 180 mL (all p < 0.001). Annual exacerbations decreased from 7.9 to 0.7, ED visits from 3.17 to 0.28, hospitalisations from 0.71 to 0.08, and maintenance OCS use from 11.8% to 3.9%. According to EXACTO, 95 patients (62.5%) achieved complete response/super-response. Independent predictors were higher baseline FEV1, higher eosinophil count, allergic rhinitis, rhinosinusitis with nasal polyps and atopic dermatitis, whereas prior OCS bursts and higher FeNO were inversely associated. Model discrimination was adequate (AUC = 0.91).

Conclusions

Dupilumab achieved clinical remission on treatment in almost two-thirds of patients with SUA and markedly reduced healthcare utilisation. A T2-comorbidity-rich profile identified patients with the highest probability of complete response.