Two‐year results of tapered dupilumab for CRSwNP demonstrates enduring efficacy established in the first 6 months

Abstract

BackgroundDupilumab 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.

Brazilian guideline for the use of immunobiologicals in chronic rhinosinusitis with nasal polyps ‒ 2024 update

“…The reduction in the impact of polyposis was greater in the group submitted to surgery (4.73 to 0.09 vs. 5.22 to 3.38). 110 Future studies may confirm this result in a larger sample of patients.…”

EUFOREA/EPOS2020 statement on the clinical considerations for chronic rhinosinusitis with nasal polyps care

“…By blocking the activity of these mediators, biologics modulate the immune response and reduce the chronic inflammation associated with the disease (including comorbidities) 57 . Biologics have been shown to reduce the size of nasal polyps, improve nasal obstruction, relieve symptoms, improve the sense of smell and improve the quality of life 48,58–61 …”

“…Based on EPOS 2020 1 and the EPOS/EUFOREA update on biologics 2023, 11 the EUFOREA expert panels recommend biologics in CRSwNP patients that are uncontrolled despite appropriate medical treatment and appropriate sinus surgery and who fulfil 3 of 5 criteria (presence of Type 2 inflammation, regular need for SCS/contra‐indications to SCS, significant impact on QOL, loss of smell and comorbid asthma). Biologics are an effective treatment with an expected improvement in the short‐term (16th week to 24th week), of at least one of the following symptom/scores: sense of smell, the nasal congestion score (NCS), the nasal polyp score (NPS), the Sino‐Nasal Outcome Test (SNOT‐22) and the visual analogue scale (VAS) 61–65 . For dupilumab, long‐term (up to 2 years) beneficial effects have been reported 59,61 .…”

“…Biologics are an effective treatment with an expected improvement in the short‐term (16th week to 24th week), of at least one of the following symptom/scores: sense of smell, the nasal congestion score (NCS), the nasal polyp score (NPS), the Sino‐Nasal Outcome Test (SNOT‐22) and the visual analogue scale (VAS) 61–65 . For dupilumab, long‐term (up to 2 years) beneficial effects have been reported 59,61 . Beneficial effects on comorbidities may be confirmed at any point of the treatment, based on the aforementioned definitions and a reduction in the need for SCS and ESS can be observed 66,67 …”

“…Overall, biologics are a safe and effective treatment option in most severe uncontrolled CRSwNP patients, with the need to properly select the patient given the high direct costs and the necessity of repeated self‐administration 48,59,61,76 …”