Dupilumab in Difficult-to-treat Chronic Spontaneous Urticaria: A Real-world Multicentre Cohort Study.

Chronic spontaneous urticaria (CSU) remains difficult to manage in patients refractory to antihistamines and omalizumab. Although dupilumab has recently been approved and incorporated into international guidelines, real-world evidence remains limited, particularly in treatment-refractory populations. We conducted a multicentre ambispective cohort study across 16 Spanish hospitals including adults with CSU, with or without concomitant chronic inducible urticaria, treated with dupilumab and followed for ≥4 weeks. The primary outcome was well-controlled disease within 24 weeks (Urticaria Control Test ≥12 and Urticaria Activity Score over 7 days≤6). Fiftyone patients were included; 92.0% had previously received omalizumab. At week 24, 69.7% (23/33) achieved well-controlled disease and 39.4% (13/33) complete control. Among patients with available week-52 data, 90.5% (19/21) and 61.9% (13/21), respectively, achieved these outcomes. Concomitant therapy use declined from 94.1% at baseline to 55.6% at week 52. Among omalizumab-experienced patients evaluable at week 24, dupilumab response was lower in prior nonresponders than in those with at least partial response to omalizumab (40% vs 85%, p=0.011). Atopic comorbidities were associated with greater UAS7 reduction (p=0.018). Dupilumab was well tolerated, with mostly mild adverse events. In routine clinical practice, dupilumab provides effective disease control in patients with difficult-totreat CSU, including most omalizumab-experienced individuals.