Clinical Longitudinal Evaluation After Regimen Stop (CLEAR) of Dupilumab in Chronic Rhinosinusitis With Nasal Polyps (CRSwNP)
Patrick Huber, Manuel Lasch, Veronika Volgger, Clemens Stihl, Philipp Teupe, Fabienne Oettgen, Sophia Gantner, Moritz GrögerABSTRACT
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.