AbstractBackgroundDupilumab is an anti‐T2‐inflammatory biological registered for chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), indicated by integrated CRS‐care pathways when optimal medico‐surgical treatment yields insufficient CRS control. This study aims to evaluate long‐term results with focus on established therapeutic efficacy while tapering dupilumab.MethodsReal‐life, prospective observational cohort study in single tertiary referral center with add‐on dupilumab as primary biological treatment in adult (≥18 years) biological‐naïve CRSwNP patients per the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS)2020‐indication with a 2‐year follow‐up. Tapering (increasing interdose interval) applied every 24 weeks, conditional to sufficient treatment response and CRS control.ResultsMean scores (s.d.) of all co‐primary outcomes improved significantly from baseline ( 228) to the 48 ( 214) and 96‐weeks ( 99) timepoints: Nasal Polyp Score (0–8) improved from 5,3 (1,9) to 1,4 (1,8) and 1,3 (1,7); SinoNasal Outcome Test (SNOT)‐22 (0–110) improved from 53,6 (19,6) to 20,2 (15,4) and 21,2 (15,6); Sniffin’Sticks‐12 identification test (0–12; 0–6 anosmia, 7–10 hyposmia, 11–12 normosmia) improved from 3,7 (2,4) to 7,7 (2,9) and 7,3 (3,04); Asthma Control Test (5–25; >19 indicating well‐controlled asthma) improved from 18,5 (4,8) to 21,8 (3,8) and 21,4 (3,9). Tapering was feasible in 79,5% of the patients at the 24‐weeks timepoint, and in 93,7% and 95,8% at the 48‐ and 96‐weeks timepoints, respectively. One‐way repeated‐measures ANOVA demonstrated no significant alterations of individual co‐primary outcome mean‐scores from 24 weeks onward.ConclusionThis first long‐term real‐life prospective observational cohort study shows high therapeutic efficacy of dupilumab for severe CRswNP in the first 2 years. Therapeutic efficacy is principally established within 24 weeks and endures while tapering dupilumab conditional to treatment response and CRS control.