Evaluating mepolizumab and dupilumab for severe chronic rhinosinusitis with nasal polyps: insights from a real-life study

Abstract

Introduction

Monoclonal antibodies (mAbs) have been effective in managing chronic rhinosinusitis with nasal polyps (CRSwNP) for over two decades, primarily as secondary treatments for severe asthma or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD). Recent approvals of biologics like mepolizumab (anti-IL5) and dupilumab (anti-IL4/IL13) now allow their use as add-on therapies for severe CRSwNP, regardless of comorbidities. However, limited data exist on their efficacy as standalone primary treatments for CRSwNP. This rea-life study investigates the potential of biologic therapies as a primary treatment for CRSwNP, focusing on multiple clinical and patient-reported outcomes.

Materials and methods

This prospective real-life study included 25 patients with severe CRSwNP, treated with mepolizumab and dupilumab indicated specifically for CRSwNP rather than associated comorbidities. Evaluations occurred at baseline and 1, 3, 6, and 12 months post-treatment, using VAS, SNOT22, and NOSE questionnaires, nasal polyp size (NPS), Lund–Kennedy scores, and BOT-8 smell tests. We also collect the data of the blood eosinophils levels before and after the treatment. Adverse events were monitored.

Results

Patients (mean age 49; 75% male; 75% N-ERD) experienced significant improvements. By 12 months, VAS scores decreased from 8.5 to 2.1, SNOT22 from 61.3 to 11, and NOSE from 69.5 to 8. Other measures, including NPS and BOT-8, also improved substantially. Specific descriptive results for each drug are also presented separately. No adverse effects were reported.

Conclusions

Biologic therapy (mepolizumab and dupilumab) as a primary treatment for CRSwNP demonstrated significant efficacy, reducing the need for surgical interventions and signaling a shift toward non-surgical management.

Resumen

Introducción

Los anticuerpos monoclonales (AAMM) han demostrado ser efectivos en el manejo de la rinosinusitis crónica con pólipos nasales (RSCcPN) durante más de dos décadas, principalmente como tratamientos secundarios en casos de asma grave o de enfermedad respiratoria exacerbada por antiinflamatorios no esteroideos (N-ERD). Las aprobaciones recientes de biológicos como mepolizumab (anti-IL5) y dupilumab (anti-IL4/IL13) permiten ahora su uso como terapias añadidas para la RSCcPN grave, independientemente de las comorbilidades. Sin embargo, existen datos limitados sobre su eficacia como tratamientos primarios en monoterapia para la CRSwNP. Este estudio en vida real investiga el potencial de las terapias biológicas como tratamiento primario de la CRSwNP, centrándose en múltiples resultados clínicos y en cuestionarios de pacientes.

Material y métodos

Este estudio prospectivo en vida real incluyó a 25 pacientes con RSCcPN grave, tratados con mepolizumab y dupilumab indicados específicamente para RSCcPN, y no por comorbilidades asociadas. Las evaluaciones se realizaron al inicio y a los 1, 3, 6 y 12 meses tras el tratamiento, utilizando las escalas visuales analógicas (EVA), SNOT-22 y NOSE, el tamaño de los pólipos nasales (NPS), la puntuación de Lund–Kennedy y las pruebas olfativas (BOT-8). También se recogieron los niveles de eosinófilos en sangre antes y después del tratamiento. Se monitorizaron los efectos adversos.

Resultados

Los pacientes (edad media 49 años; 75% varones; 75% con N-ERD) mostraron mejoras clínicas significativas. A los 12 meses, las puntuaciones EVA disminuyeron de 8,5 a 2,1; el SNOT-22 de 61,3 a 11; y el NOSE de 69,5 a 8. Otras mediciones, incluyendo el TPN y el BOT-8, también mejoraron de forma sustancial. Se presentan además resultados descriptivos específicos para cada fármaco de manera separada. No se observaron efectos adversos.

Conclusiones

La terapia biológica (mepolizumab y dupilumab) como tratamiento primario para la CRSwNP demostró una eficacia significativa, reduciendo la necesidad de intervenciones quirúrgicas y marcando una transición hacia un manejo no quirúrgico.

Introduction

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common chronic inflammatory disorder affecting approximately 3.5% of the world's population,¹ although more recent studies conducted in a subset of the Spanish population, specifically in Catalonia, report lower prevalence rates, around 0.49%.^2,3 It has a significant impact on quality of life, mainly due to loss of smell and obstruction of the upper airway. It is characterised by inflammation of the nasal mucosa and paranasal sinuses. Clinical symptoms include nasal congestion or discharge, facial pain, and loss of smell for at least 3 months. Endoscopic examination shows evidence of nasal polyps and abnormalities such as discharge and mucosal swelling in the middle turbinate.¹ It is estimated that 30–70% of people with CRSwNP also have asthma. In addition, there is a correlation between the condition of CRSwNP and a more insidious pattern of asthma with a higher degree of severity.⁴

Traditionally, the management of patients with CRSwNP has been based on two main approaches: appropriate medical treatment (intranasal corticosteroids, saline nasal lavage) and short courses of systemic steroids; and endoscopic sinus surgery. However, recent research has highlighted the need for a more targeted approach to control disease progression, with a focus on the T2 inflammatory cascade. The Type 2 pattern of inflammation is a significant contributor to the development of CRSwNP. It results in the production of certain cytokines, including IL-4, IL-5 and IL-13, which activate eosinophils, increasing the production of fibroblasts through eotaxin and B cells through IgE.⁴ Since the introduction of biologic therapy to treat CRSwNP, the management of these patients has changed radically, resulting in significant improvements in disease control and subsequent quality of life.⁶

Over the past two decades, CRSwNP has been treated with biologic therapy as an indication in severe asthma with comorbid CRSwNP in patients with severe or poorly controlled asthma managed through various therapeutic steps. Nowadays it is possible to prescribe biologic therapy as a direct indication without requiring patients to suffer from severe or uncontrolled asthma. Consequently, the number of cases eligible for treatment with this new therapy has increased. Nevertheless, its use is indicated in patients with severe CRSwNP (VAS > 7/10 and/or SNOT-22 > 50) who have previously undergone functional endoscopic sinus surgery (FESS) >6 months prior, and who meet at least one of the following criteria: presence of T2 inflammation (blood eosinophils >300 cells/µL and/or tissue eosinophils >10 cells/high power field (HPF) and/or total serum IgE >100 IU/mL); significant loss of smell (VAS > 7 cm or severe hyposmia/anosmia confirmed by olfactometry); need for oral corticosteroids or contraindication to their use (>2 cycles in the past year); and concomitant asthma and/or N-ERD with continuous use of inhaled corticosteroids.⁵

In Spain, dupilumab (a monoclonal antibody targeting IL-4 and IL-13) and mepolizumab (a monoclonal antibody targeting IL-5) are approved by the Spanish Agency for Medicines and Medical Devices (AEMPS) and have shown positive results in the literature.^7–10 At present, in our country, only patients with severe CRSwNP who had undergone two prior surgeries are eligible for public health funding. Omalizumab (a monoclonal antibody targeting IgE) is another approved biological therapy for the CRSwNP, but in Spain nowadays it doesn’t have public health funding.

For patients with severe CRSwNP who have not responded to appropriate medical treatment in combination with surgery, biological therapy is an excellent therapeutic option. Therefore, the primary objective of this study was to comprehensively assess in a real-life study the impact of mepolizumab and dupilumab on patients with severe CRSwNP, with or without comorbid asthma. This evaluation was focused on multiple outcome measures, including patient-reported symptoms, quality of life, and subjective clinical parameters. By examining these variables, the study aims to provide a thorough understanding of the therapeutic effects and potential benefits of biologics in this patient population.

Materials and methods

Study population

This observational, prospective, single-center cohort study was conducted in a real-life setting to evaluate the effectiveness of monoclonal antibody therapy (mepolizumab and dupilumab) specifically for severe chronic rhinosinusitis with nasal polyps (CRSwNP). The study took place at the Otorhinolaryngology Department of a tertiary referral hospital, with data collected from January 2022 to September 2024.

Patients were included if they met the following criteria from POLINA guidelines for biologic therapy^5,11: (i) Failure of standard medical treatment: Persistent symptoms despite optimal therapy, including continuous intranasal corticosteroids every 12 h, saline irrigations, and adequate courses of oral corticosteroids (OCS); (ii) Severe symptom burden: High symptom scores, such as a SNOT-22 score ≥50, with significant impact on nasal obstruction, rhinorrhea, olfaction, and overall quality of life; (iii) History of surgical recurrence: Recurrence of nasal polyps despite two or more prior sinus surgeries.

Patients receiving monoclonal antibody therapy for reasons other than CRSwNP (e.g., severe asthma) were excluded. All participants received appropriate medical treatment during the study, including daily intranasal corticosteroids, nasal saline irrigation, and oral corticosteroids as needed.

The decision to initiate monoclonal therapy was made by a multidisciplinary team comprising otorhinolaryngologists, pulmonologists, allergologists, immunologists, paediatricians and pharmacists. Biologic treatments included Dupilumab (300 mg biweekly) or Mepolizumab (100 mg every four weeks), both administered subcutaneously. The first two doses were supervised in the outpatient otolaryngology department for adverse event monitoring and patient education.

Patient anonymity was ensured using coded identifiers in compliance with the Declaration of Helsinki. Informed consent was obtained from all participants, and the study received ethics committee approval (code CE 148/25).

Clinical evaluation

Demographic data, including age, sex, and the presence of comorbidities such as asthma, nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD), eosinophilic otitis media and mean functional endoscopic sinus surgeries (FESS), were recorded. Information on the monoclonal antibody prescribed, follow-up duration, and related adverse events was also documented.

The following outcomes were assessed at baseline (pre-treatment) and at 1, 3, 6, and 12 months:

Nasal Symptoms and Health-Related Quality of Life (HRQoL)

• •

  Visual Analogue Scale (VAS): VAS was used to evaluate nasal the total symptoms (including obstruction, rhinorrhea and hyposmia) with scores ranging from 0 (no symptoms) to 10 (worst imaginable symptoms). It´s considered severe disease if VAS (>7 cm).⁵

• •

  Sinonasal Outcome Test (SNOT-22): This validated disease-specific HRQoL measure includes 22 items related to chronic rhinosinusitis (CRS). Each item is scored from 0 to 5, with a total score range of 0 to 110, where higher scores indicate greater symptom severity.^14,15 It´s considered severe disease if SNOT-22 > 50.⁵

• •

  Nasal Obstruction Symptom Evaluation (NOSE): The NOSE scale evaluates nasal obstruction using 5 self-reported items scored on a Likert scale (0–4). The raw score (0–20) is scaled to a total score of 0 to 100 by multiplying by 5, where higher scores reflect greater nasal obstruction severity.¹⁶

Endoscopic evaluation

• 1

  Nasal Polyp Score (NPS): Nasal polyp size was graded endoscopically for each nostril on a scale of 0 (no polyps) to 4 (large polyps causing near-complete nasal obstruction). The total NPS score ranges from 0 to 8.¹⁷

• 2

  Modified Lund–Kennedy Score: This endoscopic scoring system evaluates three parameters—polyposis, discharge, and edema—on a scale of 0 to 2 for each nostril, with higher scores indicating more severe disease.¹⁸

Olfactory evaluation

• •

  Barcelona Olfactory Test (BOT-8): Olfactory function was assessed using the BOT-8, a validated Spanish supraliminal orthonasal test. Patients were exposed to eight odorants (banana, chocolate, lemon, rose, coffee, onion, mint, and vinegar) presented in random order. Semi-solid odorants in glass vials were held approximately 3 cm below the nostrils for 3–5 seconds, with a 30-second interval between exposures. Detection, identification, and threshold were assessed.^19,20 In addition, the olfactory threshold test with phenylethyl alcohol was performed to evaluate the minimum concentration of an odorant required for detection. Patients were exposed to a series of progressively diluted phenylethyl alcohol concentrations, with responses recorded to determine the threshold level for olfactory perception.

Eosinophils in blood

In the study, we also collected data on the blood eosinophils levels from patients’ routine blood test analyses before the start of the treatment and after the treatment.

Statistical analysis

Descriptive analyses were conducted using XlStat2024. Continuous variables were summarized as means with 95% confidence intervals, while categorical variables were presented as absolute frequencies and percentages. Statistical significance was set at p < 0.05.

Nonparametric methods were applied due to the non-normal distribution of certain variables, as confirmed by the Kolmogorov–Smirnov test. The Wilcoxon signed-rank test was used to evaluate the validity of the analysis by comparing pre- and post-treatment (baseline to the last available measurement of each patient) measurements for dependent samples. This test assesses changes in medians without assuming normality, making it particularly suitable for real-world data characterized by variability and small sample sizes.

Results

Demographic data

A total of 25 patients were included in the study. Demographic and clinical characteristics of the population are presented in Table 1. The mean follow-up duration was 7.3 months (95% CI 2–11.2).

Table 1.

Demographic and clinical data, where SD, standard deviation.

	Mepolizumab	Dupilumab	Overall
N	17	8	25
Age, years	47 (SD 10,1)	52 (SD 10,7)	49 (SD 10,4)
Sex (%)
Male	13 (76,5%)	7 (87,5%)	20 (75%)
Female	4 (23,5%)	1 (12,5%)	5 (25%)
Asthma	15 (88,2%)	8 (100%)	23 (92%)
Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD)	12 (70,5%)	7 (87,5%)	19 (75%)
Eosinophilic otitis media	4 (23,5%)	1 (12,5%)	5 (20%)
Mean previous functional endoscopic sinus surgeries (FESS)	2.5	2.5	2.5

Nasal symptoms and quality of life

The mean pre-treatment total VAS score was 8.5, which progressively decreased over the months of the study. Specifically, patients treated with Mepolizumab showed a reduction in mean total VAS score from 8.5 prior to treatment initiation to 2.0 at 12 months. Regarding Dupilumab, the pre-treatment total VAS score was 8.6, which decreased to 2.3 over the course of several months (Fig. 1A).

Figure 1.

(A) Severity of total nasal symptoms in VAS (visual analogue scale) (0-10 cm) at pre-treatment and 1, 3, 6 and 12 months after treatment. The data are presented separately for the overall patient sample, the subgroup treated with Mepolizumab, and the subgroup treated with Dupilumab. (B) Sino-Nasal Outcome Test (SNOT-22) mean scores (0-110) at pre-treatment and 1, 3, 6, 12 months after treatment. The data are presented separately for the overall patient sample, the subgroup treated with Mepolizumab, and the subgroup treated with Dupilumab. (C) Nasal obstruction symptom evaluation (NOSE) mean scores (0-20) at pre-treatment and 1, 3, 6, 12 months after treatment. The data are presented separately for the overall patient sample, the subgroup treated with Mepolizumab, and the subgroup treated with Dupilumab.

The SNOT-22 mean pre-treatment score was 61.3, which progressively decreased over the months. In particular, patients receiving Mepolizumab exhibited a decline in average SNOT-22 from 63.3 at baseline to 10 after 12 months of therapy. In the case of Dupilumab, baseline SNOT-22 was recorded at 56.4, subsequently decreasing to 12 over the following months (Fig. 1B).

Similarly, the NOSE scale showed a progressive reduction from a mean of 69.5 pretreatment. Individually, patients treated with Mepolizumab showed a reduction in NOSE scale scores from 74.5 to 10.0 at 12 months. With regard to Dupilumab, patients experienced a decrease in NOSE scores from 62.5 to 6.5 after a year of treatment (Fig. 1C).

All three of these scales showed a statistically significant reduction when comparing baseline to the last available measurement (p < 0.001) (Table 2).

Table 2.

Pre- and post-treatment (last available measurement for each patient) with Mepolizumab and Dupilumab. Mean scores for different outcomes where P, Wilcoxon test comparison between pre-treatment and post-treatment mean scores; VAS, visual analogue scale; SNOT22, Sino-Nasal Outcome Test 22; NOSE, Nasal obstruction symptom evaluation; NPS, Nasal Polyp Scale; BOT-8, Barcelona olfactory test 8.

Outcome (range)	Pre-treatment mean score (Mepolizumab)	Post-treatment mean score (Mepolizumab)	P	Pre-treatment mean score (Dupilumab)	Post-treatment mean score (Dupilumab)	P
Total VAS (0−10 cm)	8.33	5.04	0.0122	8.64	2.68	0.0156
SNOT22 (0−110)	60.42	29.17	0.0024	58	13.86	0.0156
NOSE (0−20)	14.08	5.58	0.00098	12.57	2.43	0.0156
NPS (0−8)	5.67	2.78	0.0396	5.57	1.43	0.0273
Lund–Kennedy (0−12)	10.08	5.5	0.0015	10.29	1.86	0.0269
BOT- 8 Detection (0−8)	4.45	5.36	0.0574	1.57	6.0	0.0269
BOT-8 Identification (0−8)	2.55	4.64	0.058	3	5.0	0.0439
Blood eosinophils levels (eos/μL)	0,827	0,083	0.0039	0,5525	0,655	0.625

Endoscopic evaluation

Pre-treatment nasal polyp size (NPS) had a mean score of 5.63, which It gradually declined as the months of treatment progressed. When analyzing the results of both groups separately, patients treated with Mepolizumab showed a reduction in NPS from 5.7 to 2.0 at 12 months, while those receiving Dupilumab improved from 5.4 to 1.0 over the same period (Fig. 2A).

Figure 2.

(A) Lund–Kenedy mean scores (0-12) before and 1, 3, 6, 12 months after treatment. The data are presented separately for the overall patient sample, the subgroup treated with Mepolizumab, and the subgroup treated with Dupilumab. (B) Nasal Polyp Scale (NPS) mean scores (0-8) at pre-treatment and 1, 3, 6, 12 months after treatment. The data are presented separately for the overall patient sample, the subgroup treated with Mepolizumab, and the subgroup treated with Dupilumab. (C, D) Barcelona Olfactory Test (BOT-8) mean detection and identification scores (0-8) at pre-treatment and 1, 3, 6, 12 months after treatment. The data are presented separately for the overall patient sample, the subgroup treated with Mepolizumab, and the subgroup treated with Dupilumab.

The modified Lund–Kennedy score also decreased at the same time points. Patients receiving Mepolizumab demonstrated a decrease from 9.3 to 3 at the 12-month follow-up, whereas those treated with Dupilumab exhibited an improvement from 10.3 to 1.5 over the same timeframe (Fig. 2B).

A statistically significant reduction in both NPS and Lund–Kennedy scores was observed when comparing baseline to the last available measurement (p < 0.001) (Table 2).

Olfactory test

Olfactory function assessed with the BOT-8 showed a low pre-treatment mean values for detection (D) and for identification (I). Post-treatment, significant improvements were observed: patients treated with Mepolizumab improved from a detection score of 4.1 to 7.0 and an identification score of 2.2 to 7.0 at 12 months post-treatment. As for Dupilumab, patients showed an increase in detection from 5.4 to 7.5 and in identification from 1.4 to 7.5 over the same period (Fig. 2C, D). Both detection and identification scores demonstrated statistically significant improvements (p < 0.001) (Table 2). Furthermore, improvements in olfactory threshold were observed in the patient sample. The distribution of percentages showed significant differences (p = 0.036), using Friedman test (Fig. 3).

Figure 3.

Barcelona Olfactory Test (BOT-8) mean smell threshold at pre-treatment and 1, 3, 6, 12 months after treatment. Each column represents the frequency (%) of patients at different olfactory threshold levels where T0 (no smell at all), purple columns; T1 (1% odor concentration), orange columns; T2 (0.1% odor concentration), green columns; T3 (0.02% odor concentration), yellow columns, T4 (0.01% odor concentration), light blue columns; T5 (0.002% odor concentration), fuchsia columns; T6 (0.0.1% odor concentration), dark blue columns.

Eosinophils in blood

The mean count of eosinophils in blood in the Mepolizumab group was 0.827 × 10⁹/L which progressively decreased over the months of the study. Comparing baseline to the last available measurement for each patient revealed a statistically significant reduction in eosinophils in blood (p = 0.0039). However, the dupilumab group showed an increase in mean eosinophil count from 0.5525 × 10⁹/L to 0.625 × 10⁹/L throughout the study, which was not statistically significant (p = 0.625).

Safety

We analysed any adverse event that patients might have reported following the administration of the treatment. No complications or adverse effects were observed in any of the treated patients throughout the study period.

Discussion

This study presents compelling evidence on the effectiveness of biologic therapies, specifically mepolizumab and dupilumab, as primary treatments for severe chronic rhinosinusitis with nasal polyps (CRSwNP). The main findings of this real-life study can be summarized as follows: (i) Significant Improvement in quality of life: both biologics led to substantial reductions in symptom severity, as reflected by decreased VAS, SNOT-22, and NOSE scores over the study period; (ii) Reduction in nasal polyp size: endoscopic measures such as NPS and Lund–Kennedy scores showed marked reductions, demonstrating the efficacy of biologics in controlling polyp growth; (iii) enhanced olfactory function: improvements in olfaction, using the BOT-8 test, were observed, addressing a critical symptom often associated with reduced quality of life in CRSwNP patients; (iv) High Safety Profile: no adverse effects were reported in the study cohort, demonstrating the tolerability of these treatments. These findings are consistent with those reported in previous real-life studies in patients with CRSwNP.^14,21,22

To the best of our knowledge there are no previous published real-life studies on biologic therapies indicated solely by the criterion of CRSwNP in the context of European healthcare systems, particularly under public health funding constraints. This study fills this gap by offering region-specific insights.

Unlike placebo-controlled randomized trials, which often have stringent inclusion criteria that may not reflect the full spectrum of patients seen in clinical settings, this study evaluated biologics in a broader and more diverse patient population. This approach may yield more limited results, but they are more likely to accurately reflect clinical reality.^13,14

The study's focus on validated patient-reported outcomes (e.g., SNOT-22, NOSE) and olfactory function enhances its relevance, as these metrics are more reflective of patients' lived experiences than laboratory biomarkers alone. Furthermore, the inclusion of NOSE, a scale not commonly used in studies of this nature, and a validated smell test for our population (BOT-8), adds a novel dimension to the evaluation of nasal obstruction and olfaction in CRSwNP patients.

In our study, we found that biological treatments (mepolizumab and dupilumab) significantly improve quality of life, as measured by total VAS and SNOT-22, in patients with severe CRSwNP and a history of two or more surgeries. Additionally, these treatments improve the degree of nasal obstruction, assessed by the NOSE scale. These findings are consistent with improvements observed in endoscopic scales such as NPS and Lund-Kennedy. The same applies to olfaction, where significant improvement was observed as measured by BOT-8, further validating the effectiveness of these therapies in addressing a symptom with profound quality-of-life implications.^12,21–23

When comparing our patients to those in the literature, our study population had a higher prevalence of N-ERD.^6–8,12,21 Possibly due to the fact that we excluded patients treated with monoclonal therapy for other reasons, such as their asthma, and in a way selected patients with more severe CRSwNP, which is more closely associated with N-ERD, and who require monoclonal therapy.

The pretreatment mean values for VAS and SNOT-22 in our study were comparable to those reported in several studies in the literature. Moreover, randomized controlled trials have consistently demonstrated significant improvements in all these quality-of-life measures following biologic therapy.^7,8 Although direct comparisons are limited by the smaller sample size in our study, we were also able to observe these improvements shortly after initiating treatment.

This study shows significant clinical improvements within the first months of treatment, offering evidence of the rapid onset of efficacy of biologics. These findings are especially relevant for guiding clinical decisions about when to initiate treatment.

Similarly, our study demonstrated that nasal obstruction, assessed using the NOSE survey, showed a substantial decrease in scores following treatment aligning with findings reported in the literature using VAS score.^7,8,21,22 Notably, the application of the NOSE scale in this specific context has not been previously documented in the literature, adding a novel aspect to our findings, showing improvement in nasal obstruction with biologic treatments.

Beyond symptomatic relief, biologic therapies also significantly reduced polyp size, as evidenced by reductions in NPS and Lund-Kennedy scores. These results are in agreement with findings from previous studies.^21,22

We observed a significant improvement in olfactory function following biologic therapy, as reported in previous studies.^12,21–23 Importantly, we assessed olfaction by the BOT-8. Olfactory testing is often underrepresented in the literature, with the majority of studies either omitting olfactometry assessments or using tools that have not been validated for the population under study. This limitation is critical, as the identification of odors is strongly influenced by cultural factors and individual experiences. By employing the BOT-8, a validated test specifically designed for the Spanish population, our study ensures culturally appropriate and reliable measurement of olfactory changes. Additionally, by incorporating an olfactory threshold test, we were able to detect potential changes in the sense of smell with greater precision and sensitivity. This method provides a more nuanced understanding of olfactory recovery, capturing subtle improvements that might otherwise go unnoticed with less sensitive assessments.

We also can confirm that the eosinophilia in routine blood tests (conducted for other reasons) with Mepolizumab showed a significant decrease. That can be a indirectly measure of the treatment efficacy. This is also observed in other real-life studies.^14,21,22 On the other hand, dupilumab did not show significant differences in blood eosinophil levels; in fact, an increase was observed in some patients, a phenomenon already described in previous studies in the literature, without showing any adverse effects resulting from such elevation.^7,13 These differences between the two drugs may be explained by their distinct mechanisms of action.

This study has several limitations. The relatively small sample size and variable follow-up durations preclude to draw definitive conclusions. Additionally, the lack of biomarkers for stratifying patients based on treatment response represents an area for future investigation.

Another limitation of the study could be the lack of comparison between both monoclonal antibodies, as the number of patients is small and conclusions would not be generalisable to the general population.

At the time of the study, mepolizumab had higher usage among patients in our cohort, primarily due to its earlier approval for public health funding in Spain. Dupilumab, while also approved by the Spanish Agency for Medicines and Medical Devices (AEMPS) for the treatment of severe CRSwNP, was not initially funded under the public health system for this indication. However, as of May 2024, dupilumab has become eligible for public funding in Spain, which is expected to balance the number of patients receiving each treatment in the future as access improves

Future research should focus on identifying biomarkers and patient-specific characteristics to determine which patients may benefit most from early biologic treatment. This approach could reduce the reliance on repeated surgical interventions and provide a more targeted strategy for managing CRSwNP. By refining treatment selection criteria and examining long-term outcomes, future studies have the potential to further optimize patient care and improve overall quality of life.

Conclusions

In our study, Mepolizumab and Dupilimab for CRSwNP demonstrated significant improvements in nasal symptoms and quality of life (measured by VAS, SNOT-22, and NOSE), nasal polyp size (evaluated by NPS and Lund-Kennedy scores), and olfactory function (assessed using VAS and BOT-8) in patients with severe CRSwNP who had not achieved adequate disease control with conventional medical treatments or surgical interventions.

Our findings highlight the transformative potential of biologic therapies in the management of CRSwNP. These results pave the way for the development of more personalized treatment strategies, offering hope for improved outcomes in patients with refractory disease

Financial disclosure

No.