Clinical Longitudinal Evaluation After Regimen Stop (CLEAR) of Dupilumab in Chronic Rhinosinusitis With Nasal Polyps (CRSwNP).

BACKGROUND: Long-term management strategies for severe chronic rhinosinusitis with nasal polyps (CRSwNP) increasingly include biologic therapy targeting Type 2 inflammation. However, data on outcomes after complete discontinuation of dupilumab following sustained disease control are scarce. METHODS: In this single-center, retrospective real-world study, adult CRSwNP patients who discontinued dupilumab after ≥ 2 years of treatment and sustained good-to-excellent disease control were included. Disease control at cessation was defined according to EPOS/EUFOREA-aligned criteria (bilateral nasal polyp score [NPS] ≤ 2; SNOT-22 < 20). Patients were followed for up to 12 months. Outcomes included SNOT-22, visual analog scale (VAS), NPS, olfactory function (SSIT-12), relapse timing, and reinitiation of therapy. RESULTS: A total of 46 patients were included (median treatment duration 189.7 weeks). At discontinuation, disease control was excellent (mean SNOT-22 10.1 ± 6.1; NPS 0.2 ± 0.5). Within 3 months, a marked and statistically significant deterioration occurred across all major outcomes (SNOT-22 36.4 ± 20.0; VAS 5.0 ± 2.7; NPS 1.5 ± 1.9; all p < 0.001). Median time to first symptom worsening was 7.6 weeks. Most The majority of patients (87.0%) reinitiated dupilumab within 12 months, primarily due to nasal symptom recurrence. Retreatment led to rapid and significant clinical improvement. Six patients remained off therapy, but demonstrated progressive objective and/or subjective worsening over time. CONCLUSIONS: Complete discontinuation of dupilumab after long-term disease control appears feasible in only a minority of patients and is associated with early relapse in most cases. These findings support the concept of dupilumab as a disease-controlling rather than disease-modifying or curative therapy and favor individualized dose tapering over full cessation in severe Type 2-driven CRSwNP.