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

Overview

Journal Allergy

Specialty Allergy & Immunology

Date 2021 Aug 30

PMID 34459002

Citations 26

Authors

Joaquim Mullol

Tanya M Laidlaw

Claus Bachert

Leda P Mannent

G Walter Canonica

Joseph K Han

Jorge F Maspero

Cesar Picado

Nadia Daizadeh

Benjamin Ortiz

Yongtao Li

Marcella Ruddy

Elizabeth Laws

Nikhil Amin

Affiliations

Soon will be listed here.

Abstract

Background: About one-tenth of patients with difficult-to-treat chronic rhinosinusitis with nasal polyps (CRSwNP) have comorbid non-steroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD). Dupilumab, a fully human monoclonal antibody that blocks the shared interleukin (IL)-4/IL-13 receptor component, is an approved add-on treatment in severe CRSwNP. This post hoc analysis evaluated dupilumab efficacy and safety in patients with CRSwNP with/without NSAID-ERD.

Methods: Data were pooled from the phase 3 SINUS-24 and SINUS-52 studies in adults with uncontrolled severe CRSwNP who received dupilumab 300 mg or placebo every 2 weeks. CRSwNP, nasal airflow, lung function, and asthma control outcomes at Week 24 were evaluated, and treatment-subgroup interactions were assessed for patients with and without NSAID-ERD.

Results: Of 724 patients, 204 (28.2%) had a diagnosis of NSAID-ERD. At Week 24, least squares mean treatment differences demonstrated significant improvements in nasal polyp score, nasal congestion (NC), Lund-Mackay computed tomography, 22-item Sinonasal Outcome Test (SNOT-22), Total Symptom Score (TSS), rhinosinusitis severity visual analog scale, peak nasal inspiratory flow (PNIF), six-item Asthma Control Questionnaire score, and improvement in smell with dupilumab versus placebo (all p < .0001) in patients with NSAID-ERD. Treatment comparisons demonstrated significantly greater improvements with dupilumab in patients with versus without NSAID-ERD for NC (p = .0044), SNOT-22 (p = .0313), TSS (p = .0425), and PNIF (p = .0123).

Conclusions: In patients with uncontrolled severe CRSwNP, dupilumab significantly improved objective measures and patient-reported symptoms to a greater extent in the presence of comorbid NSAID-ERD than without. Dupilumab was well tolerated in patients with/without NSAID-ERD.

Citing Articles

Effect of Dupilumab in CRSwNP Sinonasal Outcomes from Real Life Studies: A Systematic Review with Meta-analysis.

Rodriguez-Iglesias M, Calvo-Henriquez C, Martin-Jimenez D, Garcia-LLiberos A, Maza-Solano J, Moreno-Luna R Curr Allergy Asthma Rep. 2025; 25(1):13.

PMID: 39907855 PMC: 11799128. DOI: 10.1007/s11882-025-01192-y.

The sinus surgery completeness score: a radiological assessment of the extent of endoscopic sinus surgery.

Gupta K, Okhovat S, Sharma R, Lim A, Beech T, McClelland L Eur Arch Otorhinolaryngol. 2024; 282(3):1301-1309.

PMID: 39627580 DOI: 10.1007/s00405-024-09110-0.

Dupilumab rapidly improves eustachian tube dysfunction and otologic symptoms in aspirin-exacerbated respiratory disease.

Mullur J, Lundberg M, Maurer R, Laidlaw T, Buchheit K Allergy Asthma Proc. 2024; 45(6):421-425.

PMID: 39517071 PMC: 11572941. DOI: 10.2500/aap.2024.45.240047.

The IL-4-IL-4Rα axis modulates olfactory neuroimmune signaling to induce loss of smell.

Hara Y, Jha M, Huang J, Han Y, Langohr I, Gaglia G Allergy. 2024; 80(2):440-461.

PMID: 39418114 PMC: 11804309. DOI: 10.1111/all.16338.

Understanding Inflammatory Heterogeneity in NSAID-Exacerbated Respiratory Disease.

Turner J, Kato A J Allergy Clin Immunol Pract. 2024; 12(11):2914-2916.

PMID: 39168300 PMC: 11629466. DOI: 10.1016/j.jaip.2024.07.035.

References

Ryan L, Segarra D, Tabor M, Parasher A . Systematic review of outcomes for endoscopic sinus surgery and subsequent aspirin desensitization in aspirin-exacerbated respiratory disease. World J Otorhinolaryngol Head Neck Surg. 2020; 6(4):220-229. PMC: 7729245. DOI: 10.1016/j.wjorl.2020.07.010. View

Stevens W, Ocampo C, Berdnikovs S, Sakashita M, Mahdavinia M, Suh L . Cytokines in Chronic Rhinosinusitis. Role in Eosinophilia and Aspirin-exacerbated Respiratory Disease. Am J Respir Crit Care Med. 2015; 192(6):682-94. PMC: 4595675. DOI: 10.1164/rccm.201412-2278OC. View

Levy J, Smith T . Is aspirin desensitization indicated for the treatment recalcitrant chronic rhinosinusitis with nasal polyposis in aspirin-exacerbated respiratory disease?. Laryngoscope. 2016; 127(4):776-777. PMC: 5360470. DOI: 10.1002/lary.26377. View

Hirano I, Dellon E, Hamilton J, Collins M, Peterson K, Chehade M . Efficacy of Dupilumab in a Phase 2 Randomized Trial of Adults With Active Eosinophilic Esophagitis. Gastroenterology. 2019; 158(1):111-122.e10. DOI: 10.1053/j.gastro.2019.09.042. View

Laidlaw T, Boyce J . Aspirin-Exacerbated Respiratory Disease--New Prime Suspects. N Engl J Med. 2016; 374(5):484-8. DOI: 10.1056/NEJMcibr1514013. View

Steinke J, Payne S, Borish L . Eosinophils and Mast Cells in Aspirin-Exacerbated Respiratory Disease. Immunol Allergy Clin North Am. 2016; 36(4):719-734. PMC: 5116300. DOI: 10.1016/j.iac.2016.06.008. View

Rabe K, Nair P, Brusselle G, Maspero J, Castro M, Sher L . Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma. N Engl J Med. 2018; 378(26):2475-2485. DOI: 10.1056/NEJMoa1804093. View

Williams A, Simon R, Woessner K, Stevenson D . The relationship between historical aspirin-induced asthma and severity of asthma induced during oral aspirin challenges. J Allergy Clin Immunol. 2007; 120(2):273-7. DOI: 10.1016/j.jaci.2007.03.020. View

Stevens W, Peters A, Hirsch A, Nordberg C, Schwartz B, Mercer D . Clinical Characteristics of Patients with Chronic Rhinosinusitis with Nasal Polyps, Asthma, and Aspirin-Exacerbated Respiratory Disease. J Allergy Clin Immunol Pract. 2017; 5(4):1061-1070.e3. PMC: 5503772. DOI: 10.1016/j.jaip.2016.12.027. View

10.

Bachert C, Han J, Wagenmann M, Hosemann W, Lee S, Backer V . EUFOREA expert board meeting on uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) and biologics: Definitions and management. J Allergy Clin Immunol. 2020; 147(1):29-36. DOI: 10.1016/j.jaci.2020.11.013. View

11.

Willsmore Z, Woolf R, Hughes C, Menon B, Kirkham B, Smith C . Development of inflammatory arthritis and enthesitis in patients on dupilumab: a case series. Br J Dermatol. 2019; 181(5):1068-1070. DOI: 10.1111/bjd.18031. View

12.

White A, Doherty T . Role of group 2 innate lymphocytes in aspirin-exacerbated respiratory disease pathogenesis. Am J Rhinol Allergy. 2018; 32(1):7-11. PMC: 5780331. DOI: 10.2500/ajra.2018.32.4498. View

13.

Choby G, OBrien E, Smith A, Barnes J, Hagan J, Stokken J . Elevated Urine Leukotriene E4 Is Associated With Worse Objective Markers in Nasal Polyposis Patients. Laryngoscope. 2020; 131(5):961-966. DOI: 10.1002/lary.29137. View

14.

Stevens W, Jerschow E, Baptist A, Borish L, Bosso J, Buchheit K . The role of aspirin desensitization followed by oral aspirin therapy in managing patients with aspirin-exacerbated respiratory disease: A Work Group Report from the Rhinitis, Rhinosinusitis and Ocular Allergy Committee of the American Academy of.... J Allergy Clin Immunol. 2020; 147(3):827-844. PMC: 7980229. DOI: 10.1016/j.jaci.2020.10.043. View

15.

Macdonald L, Karow M, Stevens S, Auerbach W, Poueymirou W, Yasenchak J . Precise and in situ genetic humanization of 6 Mb of mouse immunoglobulin genes. Proc Natl Acad Sci U S A. 2014; 111(14):5147-52. PMC: 3986150. DOI: 10.1073/pnas.1323896111. View

16.

de Wijs L, van der Waa J, de Jong P, Hijnen D . Acute arthritis and arthralgia as an adverse drug reaction to dupilumab. Clin Exp Dermatol. 2019; 45(2):262-263. DOI: 10.1111/ced.14050. View

17.

Kariyawasam H, James L, Gane S . Dupilumab: Clinical Efficacy of Blocking IL-4/IL-13 Signalling in Chronic Rhinosinusitis with Nasal Polyps. Drug Des Devel Ther. 2020; 14:1757-1769. PMC: 7217316. DOI: 10.2147/DDDT.S243053. View

18.

Castro M, Corren J, Pavord I, Maspero J, Wenzel S, Rabe K . Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma. N Engl J Med. 2018; 378(26):2486-2496. DOI: 10.1056/NEJMoa1804092. View

19.

Fokkens W, Lund V, Hopkins C, Hellings P, Kern R, Reitsma S . European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Rhinology. 2020; 58(Suppl S29):1-464. DOI: 10.4193/Rhin20.600. View

20.

Workman A, Kohanski M, Cohen N . Biomarkers in Chronic Rhinosinusitis with Nasal Polyps. Immunol Allergy Clin North Am. 2018; 38(4):679-692. PMC: 6201304. DOI: 10.1016/j.iac.2018.06.006. View