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Dupilumab suppresses type 2 inflammatory biomarkers across multiple atopic, allergic diseases
Author(s) -
Hamilton Jennifer D.,
Harel Sivan,
Swanson Brian N.,
Brian William,
Chen Zhen,
Rice Megan S.,
Amin Nikhil,
Ardeleanu Marius,
Radin Allen,
Shumel Brad,
Ruddy Marcella,
Patel Naimish,
Pirozzi Gianluca,
Mannent Leda,
Graham Neil M. H.
Publication year - 2021
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.13954
Subject(s) - eosinophilic esophagitis , periostin , medicine , dupilumab , immunology , eotaxin , eosinophil , placebo , immunoglobulin e , asthma , eosinophil cationic protein , atopic dermatitis , biomarker , tryptase , atopy , interleukin 5 , gastroenterology , interleukin , antibody , mast cell , cytokine , pathology , disease , biology , biochemistry , alternative medicine , extracellular matrix , microbiology and biotechnology
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.