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.
Adult
Anti-Inflammatory Agents, Non-Steroidal
/ adverse effects
Antibodies, Monoclonal, Humanized
/ adverse effects
Asthma
/ drug therapy
Chronic Disease
Clinical Trials, Phase III as Topic
Humans
Nasal Polyps
/ complications
Randomized Controlled Trials as Topic
Respiration Disorders
/ complications
Sinusitis
/ drug therapy
Treatment Outcome
IL-13
IL-4
chronic rhinosinusitis with nasal polyps
dupilumab
non-steroidal anti-inflammatory drug-exacerbated respiratory disease
Journal
Allergy
ISSN: 1398-9995
Titre abrégé: Allergy
Pays: Denmark
ID NLM: 7804028
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
22
12
2020
accepted:
12
08
2021
pubmed:
31
8
2021
medline:
22
4
2022
entrez:
30
8
2021
Statut:
ppublish
Résumé
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. 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. 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). 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.
Sections du résumé
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.
Identifiants
pubmed: 34459002
doi: 10.1111/all.15067
pmc: PMC9292324
doi:
Substances chimiques
Anti-Inflammatory Agents, Non-Steroidal
0
Antibodies, Monoclonal, Humanized
0
dupilumab
420K487FSG
Banques de données
ClinicalTrials.gov
['NCT02912468', 'NCT02898454']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1231-1244Informations de copyright
© 2021 Sanofi Genzyme. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
Références
World J Otorhinolaryngol Head Neck Surg. 2020 Nov 16;6(4):220-229
pubmed: 33336177
Am J Respir Crit Care Med. 2015 Sep 15;192(6):682-94
pubmed: 26067893
Laryngoscope. 2017 Apr;127(4):776-777
pubmed: 27813100
Gastroenterology. 2020 Jan;158(1):111-122.e10
pubmed: 31593702
N Engl J Med. 2016 Feb 4;374(5):484-8
pubmed: 26840139
Immunol Allergy Clin North Am. 2016 Nov;36(4):719-734
pubmed: 27712766
N Engl J Med. 2018 Jun 28;378(26):2475-2485
pubmed: 29782224
J Allergy Clin Immunol. 2007 Aug;120(2):273-7
pubmed: 17481713
J Allergy Clin Immunol Pract. 2017 Jul - Aug;5(4):1061-1070.e3
pubmed: 28286156
J Allergy Clin Immunol. 2021 Jan;147(1):29-36
pubmed: 33227318
Br J Dermatol. 2019 Nov;181(5):1068-1070
pubmed: 31017658
Am J Rhinol Allergy. 2018 Jan 1;32(1):7-11
pubmed: 29336282
Laryngoscope. 2021 May;131(5):961-966
pubmed: 33001452
J Allergy Clin Immunol. 2021 Mar;147(3):827-844
pubmed: 33307116
Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5147-52
pubmed: 24706858
Clin Exp Dermatol. 2020 Mar;45(2):262-263
pubmed: 31323136
Drug Des Devel Ther. 2020 May 08;14:1757-1769
pubmed: 32440101
N Engl J Med. 2018 Jun 28;378(26):2486-2496
pubmed: 29782217
Rhinology. 2020 Feb 20;58(Suppl S29):1-464
pubmed: 32077450
Immunol Allergy Clin North Am. 2018 Nov;38(4):679-692
pubmed: 30342588
J Clin Med. 2020 Mar 28;9(4):
pubmed: 32231056
Nat Rev Dis Primers. 2020 Oct 29;6(1):86
pubmed: 33122665
Allergy. 2019 Apr;74(4):743-752
pubmed: 30488542
Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5153-8
pubmed: 24706856
J Allergy Clin Immunol Pract. 2016 Jul-Aug;4(4):565-72
pubmed: 27393770
Lancet. 2019 Nov 2;394(10209):1638-1650
pubmed: 31543428
Am J Rhinol Allergy. 2021 May;35(3):399-407
pubmed: 32967430
J Allergy Clin Immunol. 2015 Mar;135(3):676-81.e1
pubmed: 25282015
Allergy. 2022 Apr;77(4):1231-1244
pubmed: 34459002
J Allergy Clin Immunol Pract. 2019 May - Jun;7(5):1580-1588
pubmed: 30580047
Expert Rev Clin Immunol. 2017 May;13(5):425-437
pubmed: 28277826
Allergy. 2019 Jan;74(1):28-39
pubmed: 30216468
Cochrane Database Syst Rev. 2020 Feb 27;2:CD013513
pubmed: 32102112