More than half of CRSwNP patients treated with dupilumab experience early and fast olfactory improvement within 28 days
Authors: Josje Janna Otten, Rik Johannes Leonardus van der Lans, Hester Beatrice Emilie Elzinga, Gwijde Flavius Jacobus Petrus Maria Adriaensen, Linda Berendina Laurentia Benoist, Rienk D. Hoven, Sven Seys, Wytske Johanna Fokkens, Sietze Reitsma
Journal: Allergy (2024)

Olfactory dysfunction is one of the main complaints of patients suffering from Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), significantly affecting their quality of life. In real-life studies, dupilumab effectively enhances olfactory function within 6 months of treatment.1, 2 However, the speed and efficacy of this effect on olfactory function during the initial weeks of treatment has to be determined. The data were reported in this letter stem from a prospective observational cohort (PolyREG).2 Patients from this cohort were treated with dupilumab subcutaneously (300 mg 1×/2 weeks) for CRSwNP. Patients were asked to use the Galenus Health App reporting Visual Analogue Scale (VAS) scores of their complaints in their Health Diary.3 With special regard to loss of smell, the question 'How much does smell loss bother you today?' was answered with a VAS score (0–10 cm; 0 being not bothersome at all, 10 being the most bothersome) with a cut-off of >5.2 for olfactory dysfunction.4 In total, 72 patients filled out a VAS score on olfactory dysfunction at baseline and at least another day during the first 28 days of dupilumab treatment. Also, the outcomes of the Sniffin' Sticks-12 Identification Test (SSIT-12) were collected at baseline and after 28 days of treatment. Baseline demographics of these patients are shown as repository data (Table S1). Figure 1 shows the outcomes of baseline and follow-up SSIT-12 and VAS measurements (other outcomes are listed in Table S2). At baseline, the median SSIT-12 score was 3 (IQR 2–4) indicating anosmia (Figure 1B). After 28 days, the median SSIT-12 score increased to 6 (IQR 3–9), Wilcoxon signed-rank test: p < .001, with 50% of the patients having hyposmia or normosmia (Figure 1B). Similarly, 93.7% of patients reported a VAS score on the loss of smell of >5.2 at baseline, indicating olfactory dysfunction. Over the subsequent 28 days of treatment, this percentage significantly declined to 44.2% (Figure 1: Pearson r = .924, p < .001). The mean VAS score in the first week of treatment significantly predicted the outcome of the SSIT-12 after 4 weeks of treatment (linear regression F(1,97) = 6.7, p = .01). As such, the data show a rapid olfactory function improvement in more than half of the patients treated with dupilumab, starting after 1–2 injections. Lastly, a retrospective analysis of these 72 patients' medical records was conducted to see if olfactory function improvement was previously reported by the patient during a course of oral corticosteroids (OCS) prior to initiation of dupilumab treatment.5 Data was available for 63 of 72 patients, thus giving an OCS-responsive (n = 51) (OCS-R) or OCS-unresponsive (n = 12) (OCS-U) group. The amount of previous sinus surgeries did not statistically differ between the groups (p = .60). Stratifying for OCS responsiveness showed enhanced results of dupilumab treatment in the OCS-R group (Figure 1A,B). At best, 70.8% of patients in the OCS-R group had a VAS score of ≤5.2 compared to 16.7% in the OCS-U group and 55.8% of the total cohort. While acknowledging the study's limitations, including a small patient group, missing data in the Health Diary, a cut-off corresponding not directly to SSIT-12 (Figures S1 and S2, Tables S3 and S4) and the setting in a tertiary center, the implications of our findings are profound. Dupilumab emerges as a fast, efficacious treatment option for improving olfactory function in patients with CRSwNP as it reverses inflammatory changes. Our data suggest a potential need for stratification of treatment response based on OCS responsiveness, as more patients experience olfactory function improvement if they also report it with OCS. This might be due to a corticosteroid-resistant subset of group 2 innate lymphoid cells that are probably more prevalent in OCS-unresponsive patients.6 Hester Beatrice Emilie Elzinga, Gwijde Flavius Jacobus Petrus Maria Adriaensen, Linda Berendina Laurentia Benoist, Sven Seys, and Rienk D. Hoven contributed to resources and writing – review and editing. Wytske Johanna Fokkens, Sietze Reitsma, and Rik Johannes Leonardus van der Lans contributed to conceptualization, methodology, resources, supervision, and writing – review and editing. Josje Janna Otten contributed to writing – original draft, data curation, formal analysis, and visualization. The authors would like to thank research nurses Y. te Winkel and I. Bruins for their indispensable assistance in study organization and data gathering. The patient registry PolyREG, dedicated to observational scientific research of patients treated with biologicals for chronic rhinosinusitis with nasal polyps, about which this study reports, is co-funded by the Amsterdam UMC, AERO, GSK, Novartis, and Sanofi. SR further reports grants, consulting fees, and honoraria from Sanofi and Novartis and GSK. RL further reports consulting fees from GSK. JO has acted as a consultant member for Sanofi. RL has acted as a consultant and/or advisory board member for GSK. WF is an advisory board member of and received consulting fees from Sanofi, GSK, and Dianosic. SR 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. VV has acted as a consultant and/or advisory board member for GSK. 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.