Dupilumab suppresses type 2 inflammatory biomarkers across multiple atopic, allergic diseases. Issue 7 (26th June 2021)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Clinical & experimental allergy. Volume 51:Issue 7(2021)
• Page Start: 915
• Page End: 931
• Publication Date: 2021-06-26
• Subjects: asthma -- atopic dermatitis -- chronic rhinosinusitis with nasal polyposis -- dupilumab -- eosinophilic esophagitis; Allergy -- Periodicals; Immunology -- Periodicals; 616.97
• DOI: 10.1111/cea.13954
• Languages: English
• ISSNs: 0954-7894

Abstract

Abstract: 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. Abstract : This analysis assessed dupilumab effect on biomarkers of type 2 inflammation in atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps, and eosinophilic esophagitis. Dupilumab vs. placebo suppressed thymus and activation‐regulated chemokine, total immunoglobulin E, periostin, and eotaxin‐3 in all studies/indications where assessed; blood eosinophil responses varied by disease. Dupilumab may affect a shared pathophysiological mechanism fundamental to type 2 inflammatory diseases.