Almost Half of the Dupilumab‐Treated Patients With Severe <scp>CRS</scp> With Nasal Polyps Achieve Remission in One Year
Authors: Josje J. Otten, Hester E. Elzinga, Rik J. L. van der Lans, Wytske J. Fokkens, Sietze Reitsma
Journal: Allergy (2025)

The advent of biological therapeutics has revolutionized the field of primary diffuse type 2 chronic rhinosinusitis with nasal polyps (CRSwNP). Dupilumab was the first to be available since late 2019. In line with the phase III trials, it has a high efficacy for otherwise severe and uncontrolled patients in real-world studies [1]. Data from our national database (PolyREG) show that dupilumab enables fast disease control within 6 months of treatment [2], and that this effect is maintained up to 2 years of follow-up, even when extending the dosing interval [3]. The field is now moving from the previous goal of treatment (disease control) to more audacious standards such as remission, or even cure, for which the EPOS/EUFOREA group recently proposed definitions [4]. We have performed an additional analysis of data previously published from our dupilumab cohort of 228 patients (214 with a follow-up of 1, and 99 of 2 years; all with informed consent) [3]. We translated the definitions on disease states into practical cut-offs (Appendix S1). Briefly, disease control (no bothersome complaints for the last month) was determined from patient-reported outcomes, while remission (sustained control for 12 months) was assessed using a combination of disease control, nasal endoscopy, and rescue treatments. Control and remission were determined after 1 and 2 years of treatment. After 1 year, 63.9% met the criteria for disease control. Combined with nasal endoscopy and rescue treatments, 45.7% achieved remission. After 2 years of treatment, 50.0% of patients attained disease control and 43.7% was in remission. In patients where full data were available for both time points, 35.7% was in stable remission from the first year onwards (Table 1). Tables S1 and S2 list baseline characteristics of control and remission groups per time point, respectively. Overall, no relevant differences between the groups were found at both 1- and 2-year follow-up. Notably, baseline blood eosinophils and total serum immunoglobulin E were not different between groups. As tapering of the interdose interval was applied only in case of clinical control, there were significantly more patients with intervals of over 6 weeks in the remission group (71.0%; 22/31) than in the non-remission group (35%; 14/40; p = 0.004, chi-square) at 2 years. In other words, this suggests that tapering per se does not hamper remission when used in controlled patients only. A prior history of olfactory response to oral corticosteroids (OCS) [5] only influenced the control rate at Year 1. Of note, 20%–50% of patients lacking control (precluding remission) solely due to olfactory dysfunction had no prior OCS-responsiveness (Table S3). This suggests irreversible anosmia as a direct result of CRSwNP itself or its treatment (surgery), or due to other causes (e.g., post-viral anosmia). As such, the influence of olfactory dysfunction on control and remission rates is (disproportionally) large (Tables S3 and S4). This study has limitations. The conversion of EPOS/EUFOREA definitions into practical cut-offs is not validated (further discussion hereof in Appendix S1). Ideally, specific visual analogue scales as proposed by the panel would have been used. The quantification of nasal endoscopy is limited by interrater variability and the overestimation of polyp scores when small polyps or comorbid respiratory epithelial adenomatoid hamartoma are present medial to the middle turbinate [6]. Sample size was relatively limited. Thus, further expansion and validation of cut-offs for the definition of remission is needed. Baseline prediction of remission is not possible at this moment. In conclusion, dupilumab enables almost half of the patients with severe and uncontrolled CRSwNP to attain remission in the first year of treatment. This substantiates the game changing role of biologicals in this otherwise cumbersome disease. At least for research purposes, validation of analogous quantification methods for control- and remission-definitions is needed. Josje J. Otten and Hester E. Elzinga contributed to writing – original draft, data curation, formal analysis, and visualization. Rik J. L. van der Lans, and the members of the PolyREG consortium contributed to resources and writing – review and editing. Wytske J. Fokkens and Sietze Reitsma contributed to conceptualization, methodology, resources, supervision, and writing – review and editing. The authors would like to thank research nurses Y. te Winkel and I. Bruins for their indispensable assistance in study organization and data gathering. R.J.L.L. has acted as a consultant and/or advisory board member for GSK. W.J.F. is an advisory board member of Sanofi, GSK, and Dianosic. S.R. has acted as a consultant and/or advisory board member for Sanofi, GSK, and Novartis. The department of Otorhinolaryngology and Head/Neck Surgery of the Amsterdam UMC has received research funding from Sanofi, GSK, and Novartis. M.E.C. has acted as a consultant and/or advisory board member for Sanofi, GSK, ALK, Mylan, and Medtronic. A.R. has acted as a consultant and/or advisory board member for Sanofi. J.J.O., H.E.E., I.J.K., I.K., G.F.J.P.M.A., L.B.L.B., and R.H. have no conflicts of interest to declare. PolyREG Consortium: The members of the PolyREG Consortium have enrolled patients to the study through the Nasal Polyp Register (PolyREG) database, a national, Dutch, real-time cohort database for CRSwNP patients treated with biologics. Demographics and specific clinical parameters are collected at baseline and follow-up visits in the participating medical centers. This cohort is still expanding with participating centers throughout The Netherlands. The members and centers currently include M. E. Cornet (Alrijne hospital), A. B. Rinia (Isala hospital), I. J. Kleiss (Rijnstate hospital), I. Krebbers (Maastricht University Medical Center). G. F. J. P. M. Adriaensen (Amsterdam UMC), L. B. L. Benoist (Amsterdam UMC), D. R. Hoven (Amsterdam UMC), F. C. A. Timmer (Amphia hospital). The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Appendix S1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.