“Super‐Responders” to Dupilumab Treatment in Patients With Primary Diffuse Chronic Rhinosinusitis With Nasal Polyps

ABSTRACT Background Dupilumab is effective in treating patients with type‐2 dominant chronic rhinosinusitis with nasal polyps (T2‐CRSwNP). Dosing starts at an interval of 1×/2 weeks (Q2W) with possible tapering upon disease control. Prolonging the interdose interval reduces patient burden and side effects and improves cost‐effectiveness. Objectives (1) Analyze how many patients successfully reach and maintain extended tapering of at least 1×/12 weeks (Q12W), (2) evaluate differences in baseline characteristics and clinical measurements between patients who maintain disease control on ≥ Q12W (“super‐responders”) and patients who do not; (3) compare characteristics of “super‐responders” to patients reaching Q12W but losing disease control on that dose (“excellent responders”). Method Prospective cohort study including dupilumab‐treated T2‐CRSwNP patients with a minimum follow‐up of 2.5 years. Results From a total of 198 patients, 28 (14%) were “super‐responders”, and 26 (13%) “excellent responders.” “super‐responders” had less comorbid asthma (60.7% vs. 85.9%, p < 0.001), lower baseline immunoglobulin E levels (median [Q1: Q3]: 145 [58.7; 485] vs. 313 [135.5; 746]; p = 0.007) and a shorter time since last sinus surgery (2.5 years [1; 4.8] vs. 4 years [2; 7]; p = 0.026) compared to others. No differences were observed between “excellent” and “super‐responders” at baseline, nor at the start of the Q12W interval. “excellent responders” showed worsening of clinical outcomes as well as increases in T2 markers in blood between start and stop of the Q12W interval. Conclusion Tapering of dupilumab to once every 12 weeks (Q12W) can be applied to super‐responding patients. No clear predisposing factors were identified predicting the feasibility of extended tapering.