PMID- 34037993 OWN - NLM STAT- MEDLINE DCOM- 20220228 LR - 20240403 IS - 1365-2222 (Electronic) IS - 0954-7894 (Print) IS - 0954-7894 (Linking) VI - 51 IP - 7 DP - 2021 Jul TI - Dupilumab suppresses type 2 inflammatory biomarkers across multiple atopic, allergic diseases. PG - 915-931 LID - 10.1111/cea.13954 [doi] AB - 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. CI - (c) 2021 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd. FAU - Hamilton, Jennifer D AU - Hamilton JD AUID- ORCID: 0000-0003-1236-5245 AD - Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA. FAU - Harel, Sivan AU - Harel S AD - Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA. FAU - Swanson, Brian N AU - Swanson BN AD - Sanofi, Bridgewater, NJ, USA. FAU - Brian, William AU - Brian W AD - Sanofi, Bridgewater, NJ, USA. FAU - Chen, Zhen AU - Chen Z AD - Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA. FAU - Rice, Megan S AU - Rice MS AD - Sanofi, Cambridge, MA, USA. FAU - Amin, Nikhil AU - Amin N AD - Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA. FAU - Ardeleanu, Marius AU - Ardeleanu M AD - Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA. FAU - Radin, Allen AU - Radin A AD - Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA. FAU - Shumel, Brad AU - Shumel B AD - Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA. FAU - Ruddy, Marcella AU - Ruddy M AD - Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA. FAU - Patel, Naimish AU - Patel N AD - Sanofi, Bridgewater, NJ, USA. FAU - Pirozzi, Gianluca AU - Pirozzi G AD - Sanofi, Bridgewater, NJ, USA. FAU - Mannent, Leda AU - Mannent L AD - Sanofi, Chilly-Mazarin, France. FAU - Graham, Neil M H AU - Graham NMH AD - Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA. LA - eng SI - ClinicalTrials.gov/NCT02277743 SI - ClinicalTrials.gov/NCT02277769 SI - ClinicalTrials.gov/NCT02260986 SI - ClinicalTrials.gov/NCT02414854 SI - ClinicalTrials.gov/NCT02898454 SI - ClinicalTrials.gov/NCT02379052 GR - Sanofi and Regeneron Pharmaceuticals Inc/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210626 PL - England TA - Clin Exp Allergy JT - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology JID - 8906443 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Biomarkers) RN - 0 (CCL17 protein, human) RN - 0 (CCL26 protein, human) RN - 0 (Cell Adhesion Molecules) RN - 0 (Chemokine CCL17) RN - 0 (Chemokine CCL26) RN - 0 (POSTN protein, human) RN - 37341-29-0 (Immunoglobulin E) RN - 420K487FSG (dupilumab) SB - IM MH - Antibodies, Monoclonal, Humanized/*therapeutic use MH - Biomarkers/*blood MH - Cell Adhesion Molecules/blood/drug effects MH - Chemokine CCL17/blood/drug effects MH - Chemokine CCL26/blood/drug effects MH - Eosinophils/drug effects MH - Humans MH - Hypersensitivity, Immediate/*drug therapy/*immunology MH - Immunoglobulin E/blood/drug effects MH - Inflammation/drug therapy/immunology MH - Randomized Controlled Trials as Topic PMC - PMC8362102 OTO - NOTNLM OT - asthma OT - atopic dermatitis OT - chronic rhinosinusitis with nasal polyposis OT - dupilumab OT - eosinophilic esophagitis COIS- JDH, SH, ZC, NA, MA, AR, BS and MR are employees and shareholders of Regeneron Pharmaceuticals, Inc. NMHG is a prior employee and shareholder of Regeneron Pharmaceuticals, Inc. WB, MSR, NP and LM are employees and may hold stock and/or stock options in Sanofi. BG and GP are prior employees and may hold stock and/or stock options in Sanofi. EDAT- 2021/05/27 06:00 MHDA- 2022/03/01 06:00 PMCR- 2021/08/13 CRDT- 2021/05/26 12:45 PHST- 2021/04/13 00:00 [revised] PHST- 2020/12/21 00:00 [received] PHST- 2021/04/23 00:00 [accepted] PHST- 2021/05/27 06:00 [pubmed] PHST- 2022/03/01 06:00 [medline] PHST- 2021/05/26 12:45 [entrez] PHST- 2021/08/13 00:00 [pmc-release] AID - CEA13954 [pii] AID - 10.1111/cea.13954 [doi] PST - ppublish SO - Clin Exp Allergy. 2021 Jul;51(7):915-931. doi: 10.1111/cea.13954. Epub 2021 Jun 26.