Dupilumab Treatment for Aspirin-Exacerbated Respiratory Disease in a Real-World Setting: Impact on Quality of Life and Healthcare Utilization

Abstract

Background

Patients with aspirin-exacerbated respiratory disease (AERD) have difficult-to-treat asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) and often require treatment with biologic therapy for asthma or CRSwNP. Healthcare utilization in patients with AERD has not been well described since the advent of respiratory biologics.

Objective

To determine real-world healthcare utilization and quality of life among patients with AERD and to understand the impact of dupilumab, a monoclonal antibody targeting the interleukin 4 receptor, on patient-reported health outcomes and healthcare utilization.

Methods

We conducted a longitudinal survey study of 98 patients with AERD recruited from the Brigham and Women's Hospital AERD registry. Patients completed online questionnaires describing their medication history, healthcare utilization, and quality of life every 3 months for 2 years.

Results

At the end of 24 months, participants who were on dupilumab at the start of the study and those who started dupilumab had a significant reduction in the number of reported poor health days in the preceding month compared to patients not on dupilumab (P < .001 and P < .01, respectively). Participants on dupilumab and those who started dupilumab also had significantly lower overall sinonasal outcome test-22 and asthma control test scores compared to those not on dupilumab over 24 months (P < .05 for both groups).

Conclusion

Dupilumab therapy significantly improves health-related quality of life in patients with AERD, specifically as it pertains to patient assessment of days of overall poor health and quality of life related to sinonasal and asthma symptoms.

Keywords

aspirin-exacerbated respiratory disease NSAID-exacerbated respiratory disease aspirin sensitivity chronic rhinosinusitis nasal polyps asthma respiratory biologic dupilumab quality of life eosinophilic esophagitis

Introduction

Aspirin-exacerbated respiratory disease (AERD) is characterized by eosinophilic asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and respiratory reactions to cyclooxygenase 1 (COX-1) inhibitors.¹ The clinical features of AERD are challenging to treat, with many patients experiencing exacerbation-prone asthma, nasal polyp regrowth after endoscopic sinus surgery (ESS), and high utilization of medical therapies.^1–3 Impairment in sense of smell is very common in AERD and can severely impact the physical and mental health of patients with AERD.⁴ The burden of disease in AERD often leads to substantial impairments in quality of life and increased medical resource consumption such as ESS, need for polypharmacy, and asthma-related emergency department visits or hospitalizations.^4–6

The emergence of respiratory biologics has shifted AERD treatment paradigms.^7–9 Biologics targeting type 2 inflammation are now Food and Drug Administration (FDA) approved for the treatment of severe asthma and CRSwNP.^10–17 Among these agents, dupilumab, a monoclonal antibody targeting IL-4Rα, is particularly efficacious for patients with AERD, as it leads to rapid improvements in forced expiratory volume in 1 second (FEV₁), sinonasal outcome test (SNOT)-22 scores, and smell, and reduces the frequency of asthma exacerbations.^18–21 Notably, patients with AERD who have switched to dupilumab from anti-IgE (omalizumab) or anti-IL-5/IL-5Rα (mepolizumab/benralizumab) therapy due to lack of efficacy experience greater clinical improvement with dupilumab therapy compared to the prior biologic.^2,22,23 Dupilumab has also shown efficacy in preventing post-ESS recurrence of nasal polyps in patients with AERD with previous rapid recurrence of nasal polyps after ESS, even despite aspirin desensitization.²⁴ However, the long-term impact of dupilumab therapy on health-related quality of life and healthcare utilization in AERD has not been well characterized in a real-world setting.

We conducted a real-world longitudinal survey study on the impact of dupilumab in patients with AERD, with a specific focus on overall health and respiratory disease quality of life, medication use, and healthcare utilization patterns.

Methods

We examined a cohort of 98 adults with physician-diagnosed AERD followed at the Brigham and Women's Hospital AERD Center.² Diagnosis of AERD was based on the presence of CRSwNP, asthma, and respiratory reactions to COX-1 inhibitors. 87 of the 98 participants (89%) had undergone a physician-observed aspirin challenge procedure to confirm the diagnosis. The other 11 participants had not undergone a formal drug challenge to confirm the diagnosis but had convincing clinical histories of upper or lower respiratory reactions to COX-1 inhibitors. The study was approved by the local Institutional Review Board and participants provided informed consent. Participants completed an electronic survey every 3 months for 24 months between September 2020 and September 2022, with questionnaires assessing disease status and health-related quality of life, including SNOT-22, asthma control test (ACT), and Health-Related Quality of Life (HRQOL)-4 questionnaire. Participants also reported respiratory medication utilization, emergency department (ED) visits, hospitalizations for asthma, and ESSs. Medication classes recorded included inhalers, intranasal corticosteroids, anti-leukotriene agents, antihistamines, aspirin therapy after desensitization, oral corticosteroids, and biologics. Specific medication details, including medication name and dose, were self-reported by the participants.

For baseline participant characteristics, numerical variables were compared using ANOVA tests, and categorical variables were compared using either chi-square or Fisher's exact tests. Additional patient-reported clinical history relating to co-morbidities and sinus disease severity was collected at the 9-month survey timepoint and included number of sinus surgeries, patient-reported rate of historical nasal polyp recurrence, atopic co-morbidities, and smoking history. Numerical variables were compared using ANOVA or Kruskall-Wallis tests and categorical variables were compared using chi-squared or Fisher's exact tests.

Total derived unhealthy days were calculated per Centers for Disease Control methodology and syntax for analysis and interpretation of the HRQOL-4.²⁵ Other measures were derived from responses to specific items in the HRQOL-4 questionnaire: physically unhealthy days were calculated using responses to question 2, mentally unhealthy days were calculated based on the responses to question 3, and poor health days were calculated based on responses to question 4. Negative binomial regression was used to analyze the HRQOL-4 derived measures over 24 months, as a 3-group fixed categorical variable. All 4 HRQOL-4 outcomes were over-dispersed and included excess zeros. Other covariates in the model were month as a fixed effect, baseline HRQOL-4, and interaction between month and dupilumab usage. The relationship between dupilumab usage over 24 months and total ACT and SNOT-22 scores was analyzed using repeated measures ANOVA, as a 3-group fixed categorical variable. Healthcare utilization over a 2-year period was assessed through tabulation of a total number of ED visits and hospitalizations for AERD-related medical problems in the preceding 90 days. Repeated measure ANOVA was also utilized to assess changes in medication usage over 24 months as a 3-group fixed categorical variable and a total number of medications as a numerical outcome because the data was not skewed. Generalized estimating equations model was used to analyze a relationship between dupilumab usage over 24 months as a 2-group time-changing categorical variable and oral steroid use as a dichotomized outcome. All statistical analysis was performed using SAS^® v. 9.4 (Cary, NC).

Results

Patient Characteristics

There were 40 participants on dupilumab at the start of the study; an additional 18 participants started dupilumab during the 2-year follow-up period, and 40 participants were never treated with dupilumab. There were no significant differences in age, sex, race, ethnicity, household income, health insurance coverage, or number of medications for treatment of CRSwNP and asthma between groups (Table 1).

Table 1.

Baseline Patient Characteristics.

	No dupilumab (N = 40)	Started dupilumab (N = 18)	On dupilumab at baseline (N = 40)	P-value*
Age in years, mean (SD)	51.1 (14.6)	51.3 (10.6)	52.7 (11.5)	.84
Gender				.57
Male	18 (45.0%)	6 (33.3%)	14 (35.0%)
Female	22 (55.0%)	12 (66.7%)	26 (65.0%)
Race				.82
White	34 (85.0%)	18 (100.0%)	36 (90.0%)
Black/African American	2 (5.0%)	0 (0.0%)	1 (2.5%)
Asian	0 (0.0%)	0 (0.0%)	1 (2.5%)
Other	0 (0.0%)	0 (0.0%)	1 (2.5%)
Multirace	3 (7.5%)	0 (0.0%)	1 (2.5%)
Prefer not to say	1 (2.5%)	0 (0.0%)	0 (0.0%)
Ethnicity				.41
Hispanic or Latino	0 (0.0%)	0 (0.0%)	2 (5.0%)
Not Hispanic or Latino	39 (97.5%)	17 (94.4%)	38 (95.0%)
Prefer not to say	1 (2.5%)	1 (5.6%)	0 (0.0%)
Annual household income	n = 37	n = 16	n = 36	.98
$0-35 000	2 (5.4%)	0 (0.0%)	3 (8.3%)
$35 001-70 000	6 (16.2%)	3 (18.8%)	6 (16.7%)
$70 001-105 000	7 (18.9%)	4 (25.0%)	8 (22.2%)
>$105 000	22 (59.5%)	9 (56.2%)	19 (52.8%)
Health insurance plan	n = 37	n = 17	n = 39	.78
Private	27 (73.0%)	16 (94.1%)	31 (79.5%)
Medicare/Medicaid	7 (18.9%)	1 (5.9%)	5 (12.8%)
Mass Health	2 (5.4%)	0 (0.0%)	1 (2.6%)
Other	1 (2.7%)	0 (0.0%)	2 (5.1%)
Total number of medications, mean (SD)	4.5 (1.6)	5.1 (2.0)	5.2 (1.7)	.21

Numerical variables were compared using ANOVA tests. Categorical variables were compared using either chi-square or Fisher's exact tests.

There were no significant differences in age of onset of asthma or CRSwNP diagnosis between groups (Table 2). Participants who received dupilumab were significantly more likely to have co-morbid EoE than participants not on dupilumab (chi-square test, P < .01). There was no difference in the patient-reported rate of nasal polyp recurrence following ESS or lifetime number of ESSs between groups (Table 2).

Table 2.

Clinical Characteristics of Participants Never Treated With Dupilumab, Participants Who Were on Dupilumab at Baseline, and Participants Who Started Dupilumab During the 2-Year Follow-Up Period.^a

	No dupilumab	Started dupilumab	On dupilumab at baseline	P-value*
Age of asthma diagnosis in years, mean (SD)	32.0 (14.1)	32.8 (13.6)	34.6 (14.8)	.74
Age of CRSwNP diagnosis in years, mean (SD)	36.6 (13.1)	36.1 (10.1)	38.3 (12.8)	.78
Other allergic disease, N (%)^b
Allergic rhinitis	35/37 (94.6%)	18/18 (100%)	31/36 (86.1%)	.20
Food allergy	12/37(32.4%)	4/18 (22.2%)	6/36 (16.7%)	.30
Eosinophilic esophagitis	0/37 (0.0%)	2/18 (11.1%)	8/36 (22.2%)	<.01
Atopic dermatitis	9/37 (24.3%)	6/18 (33.3%)	7/36 (19.4%)	.53
Current or former smoker	8/37 (21.6%)	5/18 (27.8%)	14/36 (38.9%)	.27
Nasal polyp recurrence < 6 months after endoscopic sinus surgery (ESS), N (%)	6/26 (23.1%)	5/15 (33.3%)	15/31 (48.4%)	.14
Lifetime number of ESS, Median (range)	2 (1-13)	2 (1-17)	3 (1-10)	.24

Not all participants in the study completed this supplementary survey.

Patient reported diagnoses, not confirmed by the treating physician.

Numerical variables were compared using ANOVA or Kruskall-Wallis tests. Categorical variables were compared using either chi-square or Fisher's exact tests.

All participants who were on dupilumab at the start of the study had been on dupilumab for < 2 years. Fifteen of the 18 patients who started dupilumab during the study period did so within the first year of the study (Table 3). There were 8 participants on other biologics at baseline: 3 on omalizumab, 4 on mepolizumab, and 1 on benralizumab. One participant on mepolizumab and 2 participants on omalizumab switched to dupilumab during the study. One participant discontinued dupilumab after the 21-month survey due to the participant's concerns about the increase in peripheral eosinophil levels.

Table 3.

Duration of Dupilumab Treatment for Patients Who Had Ever Received Dupilumab During the 2-Year Study Period.

	Number of participants
Duration of dupilumab therapy for patients on dupilumab at baseline (N = 40):
1-2 years of treatment	17
6-12 months of treatment	17
< 6 months of treatment	6
Timing of dupilumab start for patients who started during study period (N = 18)^a
Month 3	5
Month 6	4
Month 9	3
Month12	3
Month 15	1
Month 18	2

Month is the survey timepoint that the dupilumab start was reported.

All 98 participants completed the baseline survey. However, for the subsequent surveys, between 4% and 17% of participants did not respond at each time point. For the final 24-month survey, 81 of the 98 participants (82.7%) completed the survey.

Patient-Reported Quality of Life

At the end of 24 months, there was a significant reduction in the number of reported poor health days in the preceding month compared to baseline for participants on dupilumab at baseline and who started dupilumab during the study compared to patients never on dupilumab (P < .001 and P < .01, respectively, Figure 1A). There was no significant difference in the number of total derived, mentally, or physically unhealthy days between the 3 groups (Figure 1B to D). Within each of the 3 groups, there were no significant differences in HRQoL-4 derived measures at Month 24 compared to baseline. Participants who were on dupilumab at baseline and those who started dupilumab during the 24-month follow-up period had a reduction in SNOT-22 and ACT scores over 24 months compared to those not on dupilumab (P < .05 for both comparisons, Figure 2). For patients who started on dupilumab during the course of the study, mean ACT scores improved by 1.76 ± 0.72 points (P = .0155), and mean SNOT-22 scores decreased by 18.29 ± 3.09 points (P < .0001) at Month 24 compared to baseline.

Healthcare Utilization

Healthcare utilization over the 2-year period was assessed through tabulation of a total number of ED visits and hospitalizations for upper or lower respiratory disease at each survey. Throughout the study period, there were only 5 total ED visits among all participants (3 participants reporting 1 ED visit and 1 participant reporting 2 ED visits). There was only one asthma-related hospitalization among the cohort during the entire 2-year study period.

Few participants underwent ESS during the 2-year follow-up period. Two participants who never received dupilumab underwent ESS, one reported at the 6-month survey and one at the 21-month survey. Two participants who were on dupilumab underwent ESS, one reported at the 3-month survey in a patient who started dupilumab just prior to the 3-month survey, and the other reported at the 24-month survey in a patient who had been on dupilumab for over 3 years.

Medication use

At the initial survey timepoint, 85.7% of participants reported using an inhaler: 24.5% reported inhaled corticosteroid, 52% reported inhaled corticosteroid/long-acting beta-agonist, 7% reported long-acting muscarinic agonist, and 74% reported short-acting beta agonist.² At the initial survey, 62.2% of participants reported using an anti-leukotriene agent: 46.9% reported leukotriene receptor antagonist and 25.5% reported zileuton.² Fifty-nine patients (60.2%) were taking high-dose aspirin therapy after desensitization (ATAD). Seventy-two patients (73.5%) were on intranasal corticosteroids at the start of the study. There was no significant difference in healthcare utilization and patient-related quality of life measures associated with the use of nonbiologic respiratory therapies.

There were no significant differences in change total number of respiratory medications used between groups. In terms of oral corticosteroid use, 13.8% of participants who were never on dupilumab were treated with oral corticosteroids in the 3 months preceding their enrollment, compared to 22.5% of participants who received dupilumab at any time during the 2-year follow-up period (includes participants who were on dupilumab at the start of the study and those who started dupilumab during the study). In the 3-month period preceding the final survey timepoint, 12.5% of participants who never received dupilumab were treated with a course of oral corticosteroids compared to 8.2% of participants who received dupilumab. For the participants on dupilumab, the change in percentage treated with oral corticosteroids from 22.5% to 8.2% was statistically significant (OR=0.31, 95% CI: 0.11-0.87, P = .0267). For participants who were off dupilumab, use was not significantly changed: 13.8% to 12.5% (OR=1.00, 95% CI: 0.30-3.30, P = .9945). When the change from baseline to 24 months was compared between participants who were on and off dupilumab, the effect was not statistically significant (OR=0.31, 95% CI: 0.06-1.50, P = .1455) (Supplemental Table E1).

Discussion

Overall, these data demonstrate that dupilumab therapy in AERD improves long-term health-related quality of life, as measured by the HRQOL-4. Dupilumab use was associated with a significant decrease in the number of reported poor health days, indicating that with time, dupilumab therapy improves patients’ perception of their overall health. This improvement is in accord with improvements in disease-specific measures in the SNOT-22 and ACT. Most of the participants treated with dupilumab were started on dupilumab in part for severe, uncontrolled CRSwNP. During the study period, there were few ESSs recorded by participants. Dupilumab has been shown to prevent nasal polyp recurrence after ESS in patients with AERD.²⁴ Receiving dupilumab may have prevented the need for further sinus surgery in patients with a high risk for recurrence who reported historical rapid nasal polyp recurrence after ESS. A reduction in the need for surgical intervention in this high-risk group could also contribute to the noted improvements in quality of life and patient perception of health observed with dupilumab therapy.

At the end of the study period, patients on dupilumab had a significant reduction in oral corticosteroid use, with only 8.2% receiving oral corticosteroid (OCS) in the preceding 3 months, compared to 22.5% at the start of the study. This is consistent with the known steroid-sparing effect of dupilumab in severe asthma¹³ and CRSwNP.¹⁰ Notably, patients who were on or received dupilumab during the study had a higher baseline rate of OCS usage than those patients who never received dupilumab. This is likely because patients who never started dupilumab had less severe disease, and achieved adequate control of symptoms without biologic therapy. Conversely, patients who were started on dupilumab likely initiated biologic therapy due to severe disease refractory to other therapies—and are thus more likely to have experienced a recent exacerbation necessitating OCS.

Participants who received dupilumab were more likely than participants not on dupilumab to have patient-reported co-morbid EoE, but not allergic rhinitis, or atopic dermatitis. While we did not specifically query participants about treatment for EoE, it is possible that dupilumab therapy was selected by their primary treating physician over an alternative biologic to address both AERD-related respiratory disease and EoE.²⁶ It has previously been reported that patients with AERD and EoE have more rapid nasal polyp recurrence compared to patients with AERD who do not have EoE.²⁷ The observation that our participants with AERD and co-morbid EoE may have more severe sinonasal disease suggests that these participants may represent a subset of AERD characterized by more severe dysregulation of type 2 inflammation with systemic involvement. For participants in our study with AERD and comorbid EoE, the improvements in health-related quality of life with dupilumab use may reflect improvements in respiratory symptoms and EoE symptoms. All participants were treated with a dose of dupilumab of 300 mg subcutaneously every 2 weeks or less; therefore, the dose was lower than the approved dose for treatment of EoE. Thus, patients with AERD and comorbid EoE may be optimal candidates for early integration of dupilumab into their overall care, as they stand to derive multisystem benefits.

Notably, there was very low utilization of acute care services for asthma and CRSwNP in our cohort with only 5 total ED visits and 1 hospitalization during the 2-year period. This was unexpected as patients with AERD are more likely to have severe asthma, require intubation, and require treatment with systemic corticosteroids compared to aspirin-tolerant patients with asthma.²⁸ The reasons for this are likely multifactorial. First, the high biologic utilization in our AERD cohort (64% of study participants) likely impacted the frequency of asthma exacerbations and subsequent healthcare utilization compared to the prebiologic era.²⁹ Socioeconomic disparities in asthma biologic usage have been reported.^30,31 More than 75% of our participants had annual household incomes of > US$70,000 and the majority had private health insurance, which may have facilitated access to biologic therapy.³¹ While there is no statistically significant difference in the number of patients with Medicare for insurance between the 3 groups, a higher percentage of patients who had never received dupilumab had Medicare, which can also be a limitation for access to dupilumab given the high out-of-pocket prescription drug costs for patients with Medicare. Additionally, this study was initiated in September 2020, when widespread stay-at-home orders remained in place, which were associated with a reduction in exposure to environmental or viral asthma triggers.³² Lastly, patients with AERD seen at our center may have had better overall disease control because of the evaluation and targeted treatments offered at a tertiary care AERD center. This is in part supported by the baseline ACT score of > 22 for all groups, indicating that most participants had optimal asthma control throughout the study.

We did not observe a change in reported mentally or physically unhealthy days or the composite-derived unhealthy days score during the study. While prior studies have shown significant impairment in quality of life in patients with AERD,⁵ a recent study focused specifically on depression-related quality of life reported that patients with AERD had less depression and better asthma-related quality of life than patients with aspirin-tolerant asthma.³³ Participants in our cohort reported a few mentally unhealthy days at baseline, which remained stable during follow-up.

This study does have limitations. This is a real-world, pragmatic study assessing the natural course of patient outcomes over 2 years. Thus, participants initiated dupilumab therapy at different timepoints. Further, participants utilized other biologic therapies and oral corticosteroids during the study period, which can also impact measured outcomes. The disease-specific metrics (ACT, SNOT-22) are primarily patient-reported outcomes. There was attrition over the 2-year follow-up period, with variable rates of nonresponse at each time point, and only 81 participants completing the final survey, which could impact the validity of the study.³⁴ Lastly, the patient-reported information in the study, such as the patient-reported rate of nasal polyp recurrence and co-morbidities, may be subject to recall bias or patient misunderstanding of medical terminology.

Future studies should assess health-related quality of life in AERD in as it correlates with anatomic and physiologic measures of disease, in addition to immunologic biomarkers. Moreover, given the substantial cost of biologic therapy, future studies should also focus on characterizing the cost-effectiveness of dupilumab and other biologics as they relate to health-related quality of life and healthcare utilization in AERD.

In summary, this study demonstrates that over 2 years of follow-up, dupilumab therapy significantly improves patient assessment of overall poor health days in AERD, which aligns with improvements in SNOT-22 and ACT scores. These findings support the long-term benefit of dupilumab treatment for AERD.

Supplemental Material

sj-docx-1-ajr-10.1177_19458924241298817 - Supplemental material for Dupilumab Treatment for Aspirin-Exacerbated Respiratory Disease in a Real-World Setting: Impact on Quality of Life and Healthcare Utilization

Supplemental material, sj-docx-1-ajr-10.1177_19458924241298817 for Dupilumab Treatment for Aspirin-Exacerbated Respiratory Disease in a Real-World Setting: Impact on Quality of Life and Healthcare Utilization by Jyotsna Mullur, Rie Maurer, Tessa Ryan, Alanna McGill, Jillian C. Bensko, Tanya M. Laidlaw and Kathleen M. Buchheit in American Journal of Rhinology & Allergy

Footnotes

Abbreviations

Authors’ Contributions

TML, KMB, and JM designed and oversaw the study. JM and KB analyzed and interpreted data. RM conducted a statistical analysis. TR, AM, and JCB assisted in study operations and data acquisition. All authors provided final approval of the version to be published. All authors agree to be accountable for all aspects of the work related to its accuracy or integrity.

Declaration of Conflicting Interests

K.B. has served on scientific advisory boards for AstraZeneca, Sanofi, Regeneron, and GlaxoSmithKline and has received consulting fees from Genentech. T.L. has served on scientific advisory boards for AstraZeneca, Eli Lilly, Regeneron, Sanofi, and GlaxoSmithKline. J.B. has served on scientific advisory boards for GlaxoSmithKline. The other authors declare no conflicts of interest.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Regeneron, the National Institutes of Health (NIH grants U19AI095219, K23AI139352, and T32 AI007306), and by generous contributions from the Vinik and Kaye Families.

Ethical Approval

The study was approved by the Mass General Brigham Institutional Review Board and all participants provided written informed consent.

ORCID iDs

Tessa Ryan

Kathleen M. Buchheit

Supplemental Material

Supplemental material for this article is available online.

References

Berges-Gimeno

Simon

Stevenson

. The natural history and clinical characteristics of aspirin-exacerbated respiratory disease. Ann Allergy Asthma Immunol. 2002;89(5):474–478. (In eng).

Mullur

Steger

Gakpo

, et al. Aspirin desensitization and biologics in aspirin-exacerbated respiratory disease: efficacy, tolerability, and patient experience. Ann Allergy Asthma Immunol. 2022;128(5):575–582. (In eng).

White

Stevenson

. Aspirin-exacerbated respiratory disease. N Engl J Med. 2018;379(11):1060–1070.

Tchekmedyian

Lundberg

Buchheit

, et al. Loss of smell in patients with aspirin-exacerbated respiratory disease impacts mental health and quality of life. Clin Exp Allergy. 2022;52(12):1414–1421. (In eng).

White

. Survey-defined patient experiences with aspirin-exacerbated respiratory disease. J Allergy Clin Immunol Pract. 2015;3(5):711–718.

Locke

Sweis

Douglas

, et al. Treatment outcomes in aspirin-exacerbated respiratory disease based on the 12-item short form survey. Am J Rhinol Allergy. 2021;35(6):790–797.

Laidlaw

Chu

Stevens

White

. Controversies in allergy: aspirin desensitization or biologics for aspirin-exacerbated respiratory disease-how to choose. J Allergy Clin Immunol Pract. 2022;10(6):1462–1467. (In eng).

Mullur

Buchheit

. Aspirin-exacerbated respiratory disease: updates in the era of biologics. Ann Allergy Asthma Immunol. 2023;131(3):317–324.

Buchheit

Laidlaw

Levy

. Immunology-based recommendations for available and upcoming biologics in aspirin-exacerbated respiratory disease. J Allergy Clin Immunol. 2021;148(2):348–350. (In eng).

10.

Bachert

Han

Desrosiers

, et al. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): Results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials. Lancet. 2019;394(10209):1638–1650.

11.

Gevaert

Omachi

Corren

, et al. Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials. J Allergy Clin Immunol. 2020;146(3):595–605. (In eng).

12.

Han

Bachert

Fokkens

, et al. Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2021;9(10):1141–1153.

13.

Castro

Corren

Pavord

, et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med. 2018;378(26):2486–2496.

14.

Ortega

Liu

Pavord

, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014;371(13):1198–1207.

15.

Busse

Corren

Lanier

, et al. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol. 2001;108(2):184–190.

16.

Menzies-Gow

Corren

Bourdin

, et al. Tezepelumab in adults and adolescents with severe, uncontrolled asthma. N Engl J Med. 2021;384(19):1800–1809.

17.

FitzGerald

Bleecker

Nair

, et al. Benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2128–2141.

18.

Mullol

Laidlaw

Bachert

, et al. Efficacy and safety of dupilumab in patients with uncontrolled severe chronic rhinosinusitis with nasal polyps and a clinical diagnosis of NSAID-ERD: results from two randomized placebo-controlled phase 3 trials. Allergy. 2022;77(4):1231–1244. (In eng).

19.

Buchheit

Sohail

Hacker

, et al. Rapid and sustained effect of dupilumab on clinical and mechanistic outcomes in aspirin-exacerbated respiratory disease. J Allergy Clin Immunol. 2022;150(2):415–424. (In eng).

20.

Laidlaw

Mullol

Fan

, et al. Dupilumab improves nasal polyp burden and asthma control in patients with CRSwNP and AERD. J Allergy Clin Immunol Pract. 2019;7(7):2462–2465.e1. (In eng).

21.

Mustafa

Vadamalai

Scott

Ramsey

. Dupilumab as add-on therapy for chronic rhinosinusitis with nasal polyposis in aspirin exacerbated respiratory disease. Am J Rhinol Allergy. 2021;35(3):399–407.

22.

Wangberg

Spierling Bagsic

Osuna

White

. Appraisal of the real-world effectiveness of biologic therapies in aspirin-exacerbated respiratory disease. J Allergy Clin Immunol Pract. 2022;10(2):478–484 e3.

23.

Bavaro

Gakpo

Mittal

Bensko

Laidlaw

Buchheit

. Efficacy of dupilumab in patients with aspirin-exacerbated respiratory disease and previous inadequate response to anti-IL-5 or anti-IL-5R alpha in a real-world setting. J Allergy Clin Immunol Pract. 2021;9(7):2910–2912 e1.

24.

Patel

Bensko

Bhattacharyya

Laidlaw

Buchheit

. Dupilumab as an adjunct to surgery in patients with aspirin-exacerbated respiratory disease. Ann Allergy Asthma Immunol. 2022;128(3):326–328.

25.

Healthy Days Methods and Measures. ( https://archive.cdc.gov/www_cdc_gov/hrqol/methods.htm ).

26.

Dellon

Rothenberg

Collins

, et al. Dupilumab in adults and adolescents with eosinophilic esophagitis. N Engl J Med. 2022;387(25):2317–2330.

27.

Eid

Palumbo

Laidlaw

Buchheit

Cahill

. A retrospective analysis of esophageal eosinophilia in patients with aspirin-exacerbated respiratory disease. J Allergy Clin Immunol Pract. 2019;7(4):1338–1340.

28.

Mascia

Haselkorn

Deniz

, et al. Aspirin sensitivity and severity of asthma: evidence for irreversible airway obstruction in patients with severe or difficult-to-treat asthma. J Allergy Clin Immunol. 2005;116(5):970–975.

29.

Steppuhn

Langen

Scheidt-Nave

Keil

. Major comorbid conditions in asthma and association with asthma-related hospitalizations and emergency department admissions in adults: results from the German national health telephone interview survey (GEDA) 2010. BMC Pulm Med. 2013;13:46.

30.

Inselman

Jeffery

Maddux

Shah

Rank

. Trends and disparities in asthma biologic use in the United States. J Allergy Clin Immunol Pract. 2020;8(2):549–554 e1.

31.

Akenroye

Heyward

Keet

Alexander

. Lower use of biologics for the treatment of asthma in publicly insured individuals. J Allergy Clin Immunol Pract. 2021;9(11):3969–3976. (In eng).

32.

Salciccioli

She

Tulchinsky

Rockhold

Cardet

Israel

. Effect of COVID-19 on asthma exacerbation. J Allergy Clin Immunol Pract. 2021;9(7):2896–2899 e1.

33.

Feldman

Zeigler

Nelson

, et al. Depression symptoms and quality of life among individuals with aspirin-exacerbated respiratory disease. J Asthma. 2019;56(7):731–738. (In eng).

34.

Moore-Clingenpeel

Greenhawt

Shaker

. Reporting guidelines for allergy and immunology survey research. Ann Allergy Asthma Immunol. 2023;130(5):674–680 e1.

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