@article{2e5880e813c14827aa26b0a08d4c677d,
title = "From DREAM to REALITI-A and beyond: Mepolizumab for the treatment of eosinophil-driven diseases",
abstract = "Effective treatment of inflammatory diseases is often challenging owing to their heterogeneous pathophysiology. Understanding of the underlying disease mechanisms is improving and it is now clear that eosinophils play a complex pathophysiological role in a broad range of type 2 inflammatory diseases. Standard of care for these conditions often still includes oral corticosteroids (OCS) and/or cytotoxic immune therapies, which are associated with debilitating side effects. Selective, biological eosinophil-reducing agents provide treatment options that improve clinical symptoms associated with eosinophilic inflammation and reduce OCS use. Mepolizumab is a humanized monoclonal antibody that binds to and neutralizes interleukin-5, the major cytokine involved in eosinophil proliferation, activation, and survival. Mepolizumab is approved for the treatment of severe eosinophilic asthma, eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome. Additionally, the efficacy of add-on mepolizumab has been observed in patients with severe chronic rhinosinusitis with nasal polyposis and chronic obstructive pulmonary disease with an eosinophilic phenotype. Here, we review the development, approval, and real-world effectiveness of mepolizumab for the treatment of patients with severe eosinophilic asthma, from the DREAM to REALITI-A studies, and describe how knowledge from this journey extended to the use of mepolizumab and other biologics across a broad spectrum of eosinophilic diseases.",
keywords = "clinical trials, eosinophilic diseases, interleukin-5, mepolizumab, real-world data",
author = "Pavord, {Ian D.} and Bel, {Elisabeth H.} and Arnaud Bourdin and Robert Chan and Han, {Joseph K.} and Keene, {Oliver N.} and Liu, {Mark C.} and Neil Martin and Alberto Papi and Florence Roufosse and Jonathan Steinfeld and Wechsler, {Michael E.} and Yancey, {Steven W.}",
note = "Funding Information: Ian Pavord reports that he has received speaker's honoraria for sponsored meetings from AstraZeneca, Boehringer Ingelheim, Aerocrine, Almirall, Novartis, Teva, Chiesi, Sanofi/Regeneron, and GSK; and payments for organizing educational events from AstraZeneca, GSK, Sanofi/Regeneron, and Teva. He has received honoraria for attending advisory panels with Genentech, Sanofi/Regeneron, AstraZeneca, Boehringer Ingelheim, GSK, Novartis, Teva, Merck, Circassia, Chiesi, and Knopp; and payments to support FDA approval meetings from GSK. He has received sponsorship to attend international scientific meetings from Boehringer Ingelheim, GSK, AstraZeneca, Teva, and Chiesi. He has received a grant from Chiesi to support a Phase II clinical trial in Oxford. He is co‐patent holder of the rights to the Leicester Cough Questionnaire; and has received payments for its use in clinical trials from Merck, Bayer, and Insmed. In 2014–15, he was an expert witness for a patent dispute involving AstraZeneca and Teva. Elisabeth H Bel reports grants from GSK and Teva; and personal fees from AstraZeneca, GSK, Sanofi/Regeneron, Sterna Biologicals, and Chiesi. Arnaud Bourdin has received grants from Boehringer Ingelheim and AstraZeneca; has participated in clinical research projects (as an investigator) with GSK, AstraZeneca, Boehringer Ingelheim, Chiesi, Novartis, and Sanofi; and has received personal fees from GSK, AstraZeneca, Regeneron‐Sanofi, Novartis, and Chiesi. Robert Chan, Oliver N Keene, Jonathan Steinfeld, and Steven W Yancey are employees of GSK and own stocks/shares. Neil Martin is a former employee of GSK and owns stocks and shares. Joseph K Han has received consultancy fees from Sanofi Genzyme, Regeneron, Genentech, Novartis, AstraZeneca, GSK, and Gossamer Bio. Mark C Liu reports funding for clinical trials or personal fees for advisory board participation from AstraZeneca, Boehringer Ingelheim, Gossamer Bio, GSK, and MedImmune. Alberto Papi has received grants, personal fees and non‐financial support and other from AstraZeneca, Teva, Mundipharma, GSK, Chiesi, and Boehringer Ingelheim; has received personal fees and non‐financial support from Novartis, Menarini, and Zambon; and has received grants from Sanofi. Florence Roufosse reports consultancy fees from AstraZeneca and GSK; and royalties from UpToDate. Michael E Wechsler has research grants with the National Institute of Allergy and Infectious Diseases and the National Heart, Lung, and Blood Institute and is a consultant with GSK, Genentech, Sanofi, Regeneron, AstraZeneca, Teva, Novartis, Boehringer Ingelheim, Sentien, and Equillium. Funding Information: Editorial support (in the form of writing assistance, including preparation of the draft manuscript under the direction and guidance of the authors, collating and incorporating authors{\textquoteright} comments for each draft, assembling tables and figures, grammatical editing and referencing) was provided by Roisin McCorkell MSc and Elizabeth Hutchinson PhD CMPP, at Fishawack Indicia Ltd, UK, part of Fishawack Health, and was funded by GlaxoSmithKline (GSK). Publisher Copyright: {\textcopyright} 2021 GlaxoSmithKline. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.",
year = "2021",
doi = "10.1111/all.15056",
language = "English (US)",
journal = "Allergy: European Journal of Allergy and Clinical Immunology",
issn = "0105-4538",
publisher = "Wiley-Blackwell",
}