Dupilumab Monthly Dose De-Escalation Maintains Efficacy in CRSwNP

CLINICAL QUESTION

Does extending dupilumab dosing from every two weeks to every four weeks maintain clinical efficacy in patients with severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP)?

BOTTOM LINE

In a two-year real-world cohort of 148 adults with severe uncontrolled CRSwNP, extending dupilumab to monthly dosing did not compromise improvements in nasal polyp burden, symptoms, olfaction, asthma control, or quality of life. Monthly dosing appeared safe and was associated with reduced eosinophilia and improved tolerance in selected patients.

BACKGROUND: Dupilumab, a monoclonal antibody targeting IL-4/ IL-13 signaling, is standard add-on therapy for severe CRSwNP. Although approved as a 300-mg dose given every two weeks, emerging data suggest that some patients may sustain disease control with less frequent dosing. Whether dose de-escalation maintains long-term control in real-world practice remains unclear.

STUDY DESIGN: A monocentric, historical prospective real-life nonprofit study including adults with severe uncontrolled CRSwNP treated with dupilumab for at least 24 months. Patients were categorized into those maintaining standard dosing and those who extended dosing to once every four weeks after achieving sustained disease control, managing adverse events, or addressing persistent eosinophilia.

SETTING: Single tertiary academic rhinology center in Rome, Italy

SYNOPSIS: A total of 148 patients completed two years of follow-up: 77 remained on every two weeks dosing and 71 transitioned to every four weeks dosing. Both groups were similar at baseline in age, asthma prevalence, prior surgery, and severity scores. Monthly dosing was initiated between six and 18 months for varied reasons, including patient preference with sustained clinical control, persistent dupilumab-induced eosinophilia, and minor adverse events. Across the full cohort, dupilumab led to marked improvements in nasal polyp size, nasal obstruction, quality of life (SNOT-22), olfactory function (SSIT-16), and VAS symptom scores. Importantly, these improvements were sustained at 12 and 24 months in both groups, with no significant differences between two- and four-week dosing in any clinical outcome measured. Asthma control similarly remained stable in both dosing regimens. Among patients with elevated eosinophils, de-escalation was associated with reductions in eosinophil counts over the study period. Minor adverse events, particularly arthralgia, also improved following interval extension. Response categorization using EPOS/EUFOREA 2023 criteria showed comparable rates of good-to-excellent responders in both dosing groups at 24 months. These findings support the feasibility of personalized dupilumab dose de-escalation in carefully selected, stably controlled patients, while maintaining symptom control and minimizing adverse effects.

CITATION: De Corso E, et al. Dupilumab monthly dose de-escalation maintains efficacy in CRSwNP: A two-year real-world study. Laryngoscope. 2025;135(7):2267-2274. doi: 10.1002/ lary.32162