†Both authors contributed equally to this work.
Severe eosinophilic asthma (SEA) frequently coexists with chronic rhinosinusitis (CRS), with or without nasal polyps (CRSwNP/CRSsNP), exacerbating disease burden. The Sino-Nasal Outcomes Test (SNOT-22) assesses quality of life in CRS patients, but the impact of benralizumab on nasal symptoms remains controversial. This retrospective multicenter study analyzed SNOT-22 changes after 12 months of benralizumab treatment in SEA patients with comorbid CRS from the AUTOBENRA study, including data from nine Spanish hospitals. Among 121 screened SEA patients, 72 (59.5%) had CRS, with 31 providing complete SNOT-22 data pre- and posttreatment. Subjects were predominantly female (74.2%), with a mean age of 56.4 ± 13.8 years. Most (85%) had CRSwNP, 71% reported anosmia, and 67.6% had undergone functional endoscopic sinus surgery (FESS) (mean: 2.3 ± 1.7 surgeries). The baseline SNOT-22 score averaged 55.7 ± 24.6 points. After 12 months, 21 (67.7%) achieved a minimal clinically important difference (MCID; ≥12 points). Notably, anosmic subjects were more likely to achieve the MCID (82% vs 33%; P = 0.005). No significant correlations emerged between SNOT-22 improvement and demographic, clinical, or biomarker profiles.
These findings suggest that benralizumab significantly improves quality of life in SEA patients with CRS, particularly those with anosmia, regardless of baseline characteristics or biomarker levels.
Key words: benralizumab, severe eosinophilic asthma, SNOT-22, self-administration, safety
*Corresponding author: Diana Betancor Perez, Department of Allergy, University Hospital Fundación Jiménez Díaz, Madrid, Spain. Email address: [email protected]
Received 27 June 2025; Accepted 3 December 2025; Available online 1 July 2026
Copyright: Perez DB, et al.
This open access article is licensed under Creative Commons Attribution 4.0 International (CC BY 4.0). http://creativecommons.org/licenses/by/4.0/
Severe asthma is associated with chronic rhinosinusitis (CRS) with (CRSwNP) or without nasal polyps (CRSsNP) in over 35% of subjects, which significantly increases the disease burden.1 The specific sino-nasal outcomes test 22 (SNOT-22) is used to measure the quality of life in these patients.2 The addition of biologics such as benralizumab, an anti-IL-5 receptor antibody, has been shown to improve asthma control, particularly in individuals with the eosinophilic phenotype. However, the effect of this treatment on nasal symptoms remains controversial.
This study aimed to analyze the changes in SNOT-22 after 12 months of benralizumab treatment in real-life subjects with uncontrolled severe eosinophilic asthma (SEA) and comorbid CRS.
This was a retrospective multicenter study conducted in nine hospitals in Spain. It included patients with CRS and severe eosinophilic uncontrolled asthma who were treated with self-administered benralizumab as previously documented in AUTOBENRA study.3 SNOT-22 scores before and after 12 months of benralizumab treatment were analyzed, along with data on demographics, clinical characteristics, comorbidities, lung function, and asthma-related parameters (annual exacerbation rate, use of oral corticosteroids, asthma control test, quality of life).
Additionally, CRS-related characteristics were collected (number of functional endoscopic sinus surgeries, subjective anosmia, SNOT-22 questionnaire), and inflammatory biomarkers, such as total IgE, blood eosinophils, fractional exhaled nitric oxide (FeNO), and atopy status, were evaluated.
Data were analyzed using descriptive statistics, with results expressed as means with standard deviations. The normality of the data distribution was assessed using the Kolmogorov–Smirnov test. Qualitative variables were expressed as absolute numbers and relative frequencies. A comparison of demographic and clinical characteristics between groups was conducted using the Mann–Whitney U-test, Student’s t-test, chi-square test (χ2), or Fisher’s exact test, depending on the nature of the variables. The changes in quantitative characteristics between the basal and post-benralizumab states were compared using Student’s paired t-test or McNemar’s exact test. Correlations between variables and changes in SNOT-22 were calculated using Spearman’s correlation coefficient. A significance level of 5% (P < 0.05) was used for all statistical analyses, which were performed using GraphPad Prism 8 (GraphPad Software Inc., San Diego, CA, USA).
The study protocol was approved by the Ethics Committee for Research with Medicinal Products at Hospital Universitario 12 de Octubre, Madrid, Spain, under code 21/031 for the project. This study was conducted in accordance with the principles outlined in the Declaration of Helsinki.
A total of 121 subjects with severe asthma were screened, of whom 72 (59.5%) had CRS. However, only 31 had information on SNOT-22 data before and 12 months after benralizumab treatment. These 31 subjects had a mean age of 56.4 ± 13.8 years, and were predominantly females (23/31). Among them, 29 (85%) had CRSwNP and 2 had CRSsNP. The initial SNOT-22 was 55.7 ± 24.6 points. Most subjects (22/31) reported anosmia, and 23 (67.6%) had previously undergone functional endoscopic sinus surgery (FESS) with a mean of 2.3 ± 1.7 surgeries per patient. Patients with SNOT-22 measurement in the follow-up had better lung function, quality of life measured by miniAQLQ, and were less dependent on prednisone. The characteristics of these patients are summarized in Table 1.
Table 1 Baseline characteristics of the total population and the SNOT-22 subgroup.
| Demographic characteristics | Total | 12 m follow-up SNOT-22 subgroup | No SNOT-22 subgroup |
|---|---|---|---|
| 121 | 31 | 90 | |
| Female N (%) | 72 (59%) | 23 (74%) | 49 (54.1%) |
| Age, years, mean ± SD | 59.5 ± 12.5 | 56.7 ± 13.8 | 60.4 ± 13.7 |
| Never smokers N (%) | 77 (63%) | 24 (77%) | 53 (59.3%) |
| BMI | 28.2 ± 5 | 27.2 ± 4.8 | 28.6 ± 5.2 |
| Clinical characteristics | |||
| Exacerbation with treatment/year, mean ± SD | 3.2 ± 2.9 | 3.1 ± 2.7 | 3.2 ± 3.0 |
| FEV1 pre-BD, %, mean ± SD | 72.8 ± 21 | 82.4 ± 21.3* | 69.6 ± 21.3* |
| FEV1/FVC, %, mean ± SD | 70.6 ± 10.1 | 87.4 ± 25.5* | 65.4 ± 14.4* |
| ACT, mean ± SD | 15 ± 5 | 15.7 ± 4.9 | 14.8 ± 5.2 |
| Mini-AQLQ, mean ± SD | 4.1 ± 1.3 | 5.97 ± 0.8* | 3.6 ± 1.2* |
| FeNO ppb, mean ± SD | 49 ± 43 | 64.7 + 56 | 44.5 ± 43.8 |
| IgE total kU/L, mean ± SD | 540 ± 1060 | 552 + 1092 | 536 ± 1170 |
| FESS, N (%) | 32 (26) | 23 (74)** | 9 (10)** |
| Blood eosinophils/microliters, mean ± SD | 775 ± 520 | 789 ± 505 | 771 ± 530 |
| Prednisone dependent, N (%) | 34 (26) | 23 (74)** | 11 (12)** |
| Comorbidities | |||
| Atopy N (%) | 75 (62) | 23 (74) | 52 (58) |
| GERD N (%) | 46 (38) | 15 (48.8) | 31 (34) |
| Bronchiectasis N (%) | 28 (21) | 9 (29) | 19 (21) |
| N-ERD N (%) | 36 (27) | 18 (58)* | 18 (20)* |
*P < 0.05; **P < 0.001.
aACT: Asthma control test; bBMI: Body mass index; cCRSwNP: Chronic rhinosinusitis with nasal polyps; dFeNO: Fractioned exhaled nitric oxide; eFEV1: Forced exhaled volume in 1 s; fFVC: Forced vital capacity; gGERD: Gastroesophageal reflux disease; hIQR: Interquartile range; iIgE: Immunoglobulin E; jmini-AQLQ: Mini-Asthma Quality of Life Questionnaire; kN-ERD: Nonsteroidal anti-inflammatory drugs exacerbated respiratory disease; lSD: Standard deviation.
At 12 months of benralizumab treatment, the SNOT-22 score improved to an average of 25.2 ± 21.67 points, reflecting an average improvement of 30.5 points. Regarding the minimal clinically important difference (MCID) in SNOT-22, defined as an improvement of ≥12 points,2 this threshold was reached by 21 (67.7%) subjects. The baseline SNOT-22 value moderately correlated with a high NP score (r = 0.5, P < 0.05).
Subjects with subjective anosmia had worse baseline SNOT-22 scores (average 56.2 ± 26.8 points) compared to those with preserved sense of smell (average 36.8 ± 25.9; P = 0.05). Among the subjects with subjective anosmia, 18 out of 22 recovered their sense of smell after treatment, while 4 showed no changes. A higher proportion of subjects with subjective anosmia (82%) reached the MCID in SNOT-22 improvement compared to subjects with a conserved sense of smell (3/9; P = 0.005).
We found that the MCID for SNOT-22 improvement after benralizumab treatment was reached in a greater proportion of nonatopic subjects (10/11; 90%) compared to the atopic subjects (13/23; 56.5%). However, this difference was not statistically significant (P = 0.05). No other correlation with SNOT-22 values or significant MCID improvements were observed based on demographic or clinical characteristics, including disease severity, presence of exacerbations, asthma control status, or clinical remission. Similarly, no significant associations were found with biomarkers such as FeNO or peripheral eosinophilia. Results are presented in Table 2.
Table 2 Comparison of baseline characteristics between subgroups reaching and not reaching MCID in SNOT-22.
| Reaching MCID in SNOT-22 (≥12 points) | NOT reaching MCID in SNOT-22 (<11 points) |
P | |
|---|---|---|---|
| N = 21 | N = 10 | ||
| Demographic characteristics | |||
| Age, years Mean (SD) | 56.6 (14.6) | 60.2 (11.2) | n.s. |
| Sex: Female N (%) | 12 (57.1) | 8 (80) | n.s. |
| IMC Mean (SD) | 26.2 (4.2) | 29.0 (6.0) | n.s. |
| Atopy, N (%) | 11 (53.3) | 9 (90) | n.s. |
| Years with asthma, Mean (SD) | 21.6 (13.8) | 27.2 (11.6) | n.s. |
| Subjective anosmia, N (%) | 18 (85.7) | 4 (40) | 0.01 |
| Previous surgery | 17 (80.95) | 6 (60) | n.s. |
| Number of previous surgeries, Mean (SD) | 2.28 (1.69) | 2.2 (1.71) | n.s. |
| ≥ 2 surgeries | 13 (61.91) | 2 (20) | n.s. |
| ≥ 3 surgeries | 4 (19.05) | 0 (0.0) | n.s. |
| T2 Biomarkers | |||
| IgE Mean (SD) | 378.7 (595.1) | 184.0 (160.4) | n.s. |
| Highest blood eosinophils on record, Mean (SD) | 668.3 (302.1) | 990.0 (895.7) | n.s. |
| Subjects ≥ 300 eos, N (%) | 23 (100%) | 11 (100%) | n.s. |
| FeNO Mean (SD) | 64.1 (50.6) | 56.1 (65.5) | n.s. |
| Lung Function | |||
| FEV1, L Mean (SD) | 1,5 (1,2) | 2.1 (0.9) | n.s. |
| FEV1 %, Mean (SD) | 77.99 (20.0) | 89.2 (20.7) | n.s. |
| FVC, L Mean (SD) | 2.1 (1.6) | 2.8 (1.1) | n.s. |
| FVC %, Mean (SD) | 89.9 (17.6) | 104.0 (14.7) | 0.04 |
| FEV1/FVC Mean (SD) | 87.4 (17.0) | 85.1 (10.3) | n.s. |
| Clinical characteristics | |||
| Number of asthma exacerbations per year, Mean (SD) | 4.1 (3.4) | 3.8 (3.5) | n.s. |
| Clinical remission of asthma, N (%) | 12 (57.1) | 7 (70.0) | n.s. |
| ACT, Mean (SD) | 14.9 (4.1) | 17.8 (5.3) | n.s. |
| Mini AQLQ, Mean (SD) | 8.4 (16.2) | 8.5 (10.8) | n.s. |
aACT: Asthma control test; dFeNO: Fractioned exhaled nitric oxide, eFEV1: Forced exhaled volume in 1 s, fFVC: Forced vital capacity; iIgE: Immunoglobulin E; jmini-AQLQ: Mini-Asthma Quality of Life Questionnaire; lSD: Standard deviation.
Real-life improvement in SNOT-22 scores following benralizumab treatment has been demonstrated in other studies, with reductions of −19.8 reported by Le et al.4 and by Chitguppi et al.5 of −21.4 points. These improvements are lower than the −30.5 points observed in our study. Notably, both studies used a lower MCID threshold in SNOT-22 of nine points, whereas our study applied the cutoff point based on the Spanish expert consensus guidelines. We hypothesize that the anti-IL-5R mechanism of action of benralizumab may be insufficient to fully block the IgE-mediated inflammatory cascade associated with allergic rhinitis. In the RANS study,4 67.6% of participants with SEA and CRSwNP achieved the MCID for SNOT-22 improvement. The lower proportion of subjects with allergic rhinitis (13.3%) in the RANS study compared to our population (64.5%) may explain the reduced success rate in our atopic subjects.
Our population and the study by Chitguppi et al.5 included a higher proportion of subjects with prior FESS (74 and 87%, respectively) compared to Le et al.’s population (65.7%). This difference may explain why benralizumab appears to yield a greater reduction in SNOT-22 scores in subjects who have undergone FESS.
The limitations of this study include the retrospective design and the small sample size, which likely restricted the statistical significance of some correlations between clinical characteristics or biomarkers. Nonetheless, our analysis is valuable as it highlights trends near statistical significance, which could be further investigated in larger sample sizes.
We conclude that benralizumab is effective in improving the quality of life, as measured by SNOT-22, in individuals with severe uncontrolled eosinophilic asthma and comorbid CRS, especially among those experiencing subjective anosmia. The improvement is evident regardless of other clinical characteristics or biomarker levels.
The Ethics Committee for Research with Medicinal Products at Hospital Universitario 12 de Octubre, Madrid, Spain, approved the study protocol and assigned code 21/031 to the project. Signed informed consent from all subjects was included as an inclusion criterion.
The authors declare that no AI-assisted tools were used in the preparation of this manuscript. All references have been manually verified for accuracy and relevance.
All authors contributed equally to this article.
The authors declare no potential conflicts of interest with respect to the publication of this article.
This research did not receive any specific grant from the funding agencies in public, commercial, or not-for-profit sectors. The AIRE Group meetings were sponsored by AstraZeneca.
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