Dupilumab suppresses type 2 inflammatory biomarkers across multiple atopic, allergic diseases.
Antibodies, Monoclonal, Humanized
/ therapeutic use
Biomarkers
/ blood
Cell Adhesion Molecules
/ blood
Chemokine CCL17
/ blood
Chemokine CCL26
/ blood
Eosinophils
/ drug effects
Humans
Hypersensitivity, Immediate
/ drug therapy
Immunoglobulin E
/ blood
Inflammation
/ drug therapy
Randomized Controlled Trials as Topic
asthma
atopic dermatitis
chronic rhinosinusitis with nasal polyposis
dupilumab
eosinophilic esophagitis
Journal
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
ISSN: 1365-2222
Titre abrégé: Clin Exp Allergy
Pays: England
ID NLM: 8906443
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
revised:
13
04
2021
received:
21
12
2020
accepted:
23
04
2021
pubmed:
27
5
2021
medline:
1
3
2022
entrez:
26
5
2021
Statut:
ppublish
Résumé
Type 2 inflammation is common in numerous atopic/allergic diseases and can be identified by elevated biomarker levels. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key and central drivers of type 2 inflammation. Assessment of dupilumab effect on type 2 inflammatory biomarkers in atopic dermatitis (AD), asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and eosinophilic esophagitis (EoE). Data were extracted from three randomized placebo-controlled trials of dupilumab in AD (NCT02277743, N = 671; NCT02277769, N = 708; NCT02260986, N = 740); and one each in asthma (NCT02414854, N = 1902); CRSwNP (NCT02898454, N = 448); and EoE (NCT02379052, N = 47). Biomarkers assessed were serum thymus and activation-regulated chemokine (TARC), plasma eotaxin-3, serum total immunoglobulin E (IgE), serum periostin and blood eosinophil count. Dupilumab versus placebo significantly suppressed most type 2 inflammatory biomarker levels across all studies/indications where data were assessed. Reductions in serum TARC, plasma eotaxin-3 and serum periostin occurred rapidly, whereas reductions in serum total IgE were more gradual. Across diseases, at the end of treatment, median percentage change from baseline in TARC levels ranged from -24.8% to -88.6% (placebo +2.6% to -53.6%); -38.2% to -51.5% (placebo +8.3% to -0.16%) in eotaxin-3; -24.8% to -76.7% (placebo +8.3% to -4.4%) in total IgE; and -13.6% to -41.1% (placebo +10.1% to -6.94%) in periostin levels. Blood eosinophil responses to dupilumab varied by disease, with minimal changes in AD in the SOLO studies (median percentage change from baseline to end of treatment: 0% [95% CI: -15.8, 0]); transient increases followed by decreases to below-baseline levels in asthma (-14.6% [-20.0, -7.7]) and CRSwNP (-29.4% [-40.0, -16.3]); and significant decreases in EoE (-50.0% [-50.0, -33.3]). Dupilumab reduced levels of type 2 biomarkers across clinical studies in patients with AD, asthma, CRSwNP and EoE.
Sections du résumé
BACKGROUND
Type 2 inflammation is common in numerous atopic/allergic diseases and can be identified by elevated biomarker levels. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key and central drivers of type 2 inflammation.
OBJECTIVE
Assessment of dupilumab effect on type 2 inflammatory biomarkers in atopic dermatitis (AD), asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and eosinophilic esophagitis (EoE).
METHODS
Data were extracted from three randomized placebo-controlled trials of dupilumab in AD (NCT02277743, N = 671; NCT02277769, N = 708; NCT02260986, N = 740); and one each in asthma (NCT02414854, N = 1902); CRSwNP (NCT02898454, N = 448); and EoE (NCT02379052, N = 47). Biomarkers assessed were serum thymus and activation-regulated chemokine (TARC), plasma eotaxin-3, serum total immunoglobulin E (IgE), serum periostin and blood eosinophil count.
RESULTS
Dupilumab versus placebo significantly suppressed most type 2 inflammatory biomarker levels across all studies/indications where data were assessed. Reductions in serum TARC, plasma eotaxin-3 and serum periostin occurred rapidly, whereas reductions in serum total IgE were more gradual. Across diseases, at the end of treatment, median percentage change from baseline in TARC levels ranged from -24.8% to -88.6% (placebo +2.6% to -53.6%); -38.2% to -51.5% (placebo +8.3% to -0.16%) in eotaxin-3; -24.8% to -76.7% (placebo +8.3% to -4.4%) in total IgE; and -13.6% to -41.1% (placebo +10.1% to -6.94%) in periostin levels. Blood eosinophil responses to dupilumab varied by disease, with minimal changes in AD in the SOLO studies (median percentage change from baseline to end of treatment: 0% [95% CI: -15.8, 0]); transient increases followed by decreases to below-baseline levels in asthma (-14.6% [-20.0, -7.7]) and CRSwNP (-29.4% [-40.0, -16.3]); and significant decreases in EoE (-50.0% [-50.0, -33.3]).
CONCLUSION AND CLINICAL RELEVANCE
Dupilumab reduced levels of type 2 biomarkers across clinical studies in patients with AD, asthma, CRSwNP and EoE.
Identifiants
pubmed: 34037993
doi: 10.1111/cea.13954
pmc: PMC8362102
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Biomarkers
0
CCL17 protein, human
0
CCL26 protein, human
0
Cell Adhesion Molecules
0
Chemokine CCL17
0
Chemokine CCL26
0
POSTN protein, human
0
Immunoglobulin E
37341-29-0
dupilumab
420K487FSG
Banques de données
ClinicalTrials.gov
['NCT02277743', 'NCT02277769', 'NCT02260986', 'NCT02414854', 'NCT02898454', 'NCT02379052']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
915-931Subventions
Organisme : Sanofi and Regeneron Pharmaceuticals Inc
Informations de copyright
© 2021 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.
Références
Lancet Respir Med. 2021 Jun 25;:
pubmed: 34181876
Sci Signal. 2008 Dec 23;1(51):pe55
pubmed: 19109238
Ann Allergy Asthma Immunol. 2017 May;118(5):582-590.e2
pubmed: 28366582
J Allergy Clin Immunol. 2001 Mar;107(3):429-40
pubmed: 11240941
Int J Dermatol. 2015 Jul;54(7):e261-5
pubmed: 26108268
Expert Rev Clin Immunol. 2017 May;13(5):425-437
pubmed: 28277826
Nat Rev Drug Discov. 2013 Feb;12(2):117-29
pubmed: 23334207
J Dermatol Sci. 2019 May;94(2):266-275
pubmed: 31109652
JAMA. 2016 Feb 2;315(5):469-79
pubmed: 26836729
Thorax. 2003 Feb;58(2):175-82
pubmed: 12554905
Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5147-52
pubmed: 24706858
Allergy. 2018 Jun;73(6):1331-1336
pubmed: 29380876
Curr Allergy Asthma Rep. 2016 Feb;16(2):9
pubmed: 26758862
J Immunol. 2006 Apr 1;176(7):4352-60
pubmed: 16547273
Thorax. 1996 Feb;51(2):218-20
pubmed: 8711662
N Engl J Med. 2018 Jun 28;378(26):2486-2496
pubmed: 29782217
Allergy. 2020 May;75(5):1188-1204
pubmed: 31838750
Allergy. 2019 Apr;74(4):743-752
pubmed: 30488542
JAKSTAT. 2013 Oct 1;2(4):e25301
pubmed: 24416647
Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5153-8
pubmed: 24706856
J Immunol. 1992 Feb 15;148(4):1086-92
pubmed: 1371130
J Allergy Clin Immunol. 2017 Sep;140(3):710-719
pubmed: 28089872
Adv Ther. 2018 May;35(5):737-748
pubmed: 29725983
J Physiol Pharmacol. 2003 Dec;54(4):469-87
pubmed: 14726604
Nat Rev Drug Discov. 2016 Jan;15(1):35-50
pubmed: 26471366
JAMA Pediatr. 2020 Jan 1;174(1):15-16
pubmed: 31764954
Gastroenterology. 2020 Jan;158(1):111-122.e10
pubmed: 31593702
Eur J Immunol. 2006 Jul;36(7):1882-91
pubmed: 16810739
J Biol Chem. 2018 Sep 21;293(38):14646-14658
pubmed: 30076218
Lancet. 2019 Nov 2;394(10209):1638-1650
pubmed: 31543428
Pediatr Allergy Immunol. 2012 May;23(3):278-84
pubmed: 22017510
J Asthma Allergy. 2020 Dec 16;13:701-711
pubmed: 33364789
J Allergy Clin Immunol. 2019 Jan;143(1):155-172
pubmed: 30194992
J Allergy Clin Immunol Pract. 2018 Sep - Oct;6(5):1528-1533
pubmed: 29954692
N Engl J Med. 2014 Jul 10;371(2):130-9
pubmed: 25006719
N Engl J Med. 2016 Dec 15;375(24):2335-2348
pubmed: 27690741
J Allergy Clin Immunol. 2013 May;131(5):1350-60
pubmed: 23541327
N Engl J Med. 2018 Jun 28;378(26):2475-2485
pubmed: 29782224
N Engl J Med. 2015 Oct 22;373(17):1640-8
pubmed: 26488694
Clin Exp Allergy. 2017 Feb;47(2):161-175
pubmed: 28036144
J Allergy Clin Immunol Pract. 2020 Feb;8(2):527-539.e9
pubmed: 31351189
Clin Exp Allergy. 2021 Jul;51(7):915-931
pubmed: 34037993
Int Immunol. 2018 Aug 30;30(9):403-412
pubmed: 30053010
Nat Rev Immunol. 2015 Jan;15(1):57-65
pubmed: 25534623
Acta Derm Venereol. 2010 Nov;90(6):589-94
pubmed: 21057741
Lancet. 2017 Jun 10;389(10086):2287-2303
pubmed: 28478972
J Allergy Clin Immunol. 2014 Dec;134(6):1293-1300
pubmed: 25482871
Cell Mol Life Sci. 2017 Dec;74(23):4293-4303
pubmed: 28887633
Clin Rev Allergy Immunol. 2019 Aug;57(1):111-127
pubmed: 30903437