Long-term effects of dupilumab on chronic rhinosinusitis with nasal polyps: A step towards clinical remission

Abstract

Background and objectives: Clinical remission, defined as the absence of disease activity and symptoms, is an emerging goal in the management of chronic rhinosinusitis with nasal polyps (CRSwNP). This study aimed to evaluate the long-term effects of dupilumab on patients with CRSwNP, with or without asthma, and explore the potential for achieving clinical remission.

Methods: A two-year prospective study was conducted on 109 patients with CRSwNP, with or without asthma, who were eligible for dupilumab as an add-on therapy. Comprehensive assessments, including clinical, laboratory, and radiological evaluations, were performed before and after treatment. Clinical remission of CRSwNP was defined as 12 months of dupilumab treatment, no exacerbations requiring oral corticosteroids (OCS), no need for nasal sinus operation, no anosmia or hyposmia, a Sino-Nasal Outcome Test (SNOT-22) score under 20, and a Lund-Mackay score (LMS) below 10. For those with comorbid asthma, clinical remission was defined as an asthma control test (ACT) score of 19 or higher, no asthma exacerbations, and no need for OCS.

Results: Dupilumab significantly improved CRSwNP outcomes in both groups, including SNOT-22 scores, nasal polyp size (LMS), and anosmia/hyposmia. Comorbid asthma was highly prevalent (79.8%), and patients with asthma had significantly larger nasal polyps, both before and after dupilumab therapy, despite similar symptom improvement. Higher fractional exhaled nitric oxide (FeNO) and blood eosinophil count (BEC) levels, along with anosmia/hyposmia, predicted larger polyp size. Dupilumab also significantly improved asthma outcomes, increasing forced expiratory volume in 1 s (FEV1) and decreasing FeNO. Clinical remission was achieved in 11% of patients, with a slightly lower rate in those with asthma (7.3%).

Conclusion: Dupilumab treatment can achieve clinical remission in CRSwNP. However, comorbid asthma appears to reduce the likelihood of remission and is associated with larger nasal polyps, even with similar symptom improvement. Asthma may independently influence polyp development, potentially impacting long-term outcomes in CRSwNP.

Keywords: Chronic rhinosinusitis; Clinical remission; Comorbid asthma; Dupilumab; Lund-mackay score; Nasal polyps.

Fig. 1

ROC curve of LMS to detect the associate comorbid asthma in CRSwNP patients. AUC: area under curve, Sens.: sensitivity, Spec.: specificity, p < 0.05 considered significant.

Fig. 2

Effect of dupilumab on SNOT-22, FeNO, BEC and total IgE in patients with CRSwNP SNOT-22: Sino-Nasal Outcome Test, FeNO: fractional exhaled nitric oxide, ppb: part per million, BEC: blood eosinophil count, IgE: Immune globulin E, the test of significant: Mann Whitney test, p < 0.05 considered significant. Recruitment period (0–12 months), and follow-up period (12–24 months).

Fig. 3

Effect of dupilumab on the frequency of anosmia/hyposmia and OCS use in patients with CRSwNP OCS: oral corticosteroid, the test of significant: Chi square test, p < 0.05 considered significant. Recruitment period (0–12 months), and follow-up period (12–24 months).

Fig. 4

Impact of dupilumab on LMS and its trend of reduction with treatment duration LMS: Lund Macke score, the test of significant: Mann Whitney test, p < 0.05 considered significant. Recruitment period (0–12 months), and follow-up period (12–24 months).

Fig. 5

Changes in CT-PNS before and after dupilumab In the (A) collection, the figure showed complete and partial opacification of PNS, the LMS was above 10, however, in the (B) collection, the effect of dupilumab was obvious; the figure showed absence or even mild opacification of both maxillary and both sphenoid sinuses with clear frontal, anterior ethmoid, posterior ethmoid with non-obstructed ostiomeatal complexes, with a score of less than 10 of 24 according to LMS. Recruitment period (0–12 months), and follow-up period (12–24 months).

Fig. 6

Effect of dupilumab on asthma control and airway obstruction ACT: Asthma control test score, FEV1: Forced expiratory flow in 1 s, FVC: Forced expiratory capacity, the test of significant: Mann Whitney test, p < 0.05 considered significant. Recruitment period (0–12 months), and follow-up period (12–24 months).