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Defining a Severe Asthma Super-Responder: Findings from a Delphi Process

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the Delphi Panel, John W. Upham, Chantal Le Lievre, David J. Jackson, Matthew Masoli, Michael E. Wechsler, David B. Price, Adel Mansur, Aikaterini Detoraki, Alan Altraja, Alan James, Alexandra Nanzer-Kelly, Andréanne Côté, Andrew Menzies-Gow, Andriana Papaioannou, Anne Maree Cheffins, Arnaud Bourdin, Bassam Mahboub, Brian Lipworth, Carlos Andrés Celis-Preciado & 31 more Carlos Torres-Duque, Caterina Bucca, Celeste Porsbjerg, Charlotte Ulrik, Chris Corrigan, Christian Taube, Claude Farah, Constance Katelaris, David Langton, Dermot Ryan, Désirée Larenas-Linnemann, Eleftherios Zervas, Enrico Heffler, Flavia Hoyte, Francesca Puggioni, George Christoff, Giorgio Walter Canonica, Giovanna Elisiana Carpagnano, Giuseppe Guida, Gregory Katsoulotos, Guy Brusselle, Hitashi Rupani, Hubertus Jersmann, Ian Clifton, Jaideep Dhariwal, James Fingleton, Jane Duke, Janet Rimmer, Jo Douglass, Maria Conte, Paul Pfeffer

Original languageEnglish
Pages (from-to)3997-4004
Number of pages8
JournalJournal of Allergy and Clinical Immunology: In Practice
Volume9
Issue number11
DOIs
Accepted/In press2021
PublishedNov 2021

Bibliographical note

Funding Information: Conflicts of interest: J.W. Upham reports personal fees from AstraZeneca, GlaxoSmithKline, Sanofi, Boehringer Ingelheim, and Novartis, outside the submitted work. D.J. Jackson reports personal fees from AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Teva, Napp, Chiesi, and Novartis; and grants from AstraZeneca , outside the submitted work. M. Masoli reports personal fees from Novartis and AstraZeneca, outside the submitted work. M.E. Wechsler reports grants and personal fees from Novartis , Sanofi , and Cohero Health ; personal fees from Regeneron, Genentech, Sentien, Restorbio, Equillium, and Genzyme; grants, personal fees, and nonfinancial support from Teva and AstraZeneca ; personal fees and nonfinancial support from Boehringer Ingelheim ; and personal fees from GSK, outside the submitted work. D.B. Price reports grants from AKL Research and Development Ltd , British Lung Foundation , Respiratory Effectiveness Group , and UK National Health Service ; grants and personal fees from AstraZeneca , Boehringer Ingelheim , Chiesi , Mylan , Novartis , Regeneron Pharmaceuticals , Sanofi Genzyme , Theravance , Zentiva (Sanofi Generics); personal fees from Cipla, GlaxoSmithKline, Kyorin, Merck, Mundipharma, Airway Vista Secretariat, EPG Communication Holdings Ltd, FIECON Ltd, Fieldwork International, OM Pharma SA, PeerVoice, Phadia AB, Spirosure Inc, Strategic North Limited, Synapse Research Management Partners S.L, Talos Health Solutions, and WebMD Global LLC, outside the submitted work; nonfinancial support from Efficacy and Mechanism Evaluation programme and Health Technology Assessment; and stock/stock options from AKL Research and Development Ltd, which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 92.61% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); and 5% shareholding in Timestamp, which develops adherence monitoring technology. The rest of the authors declare that they have no relevant conflicts of interest. Funding Information: This project was supported by in kind contributions from the Observational and Pragmatic Research Institute and the University of Queensland Faculty of Medicine . No pharmaceutical companies were involved in the study design or execution. Funding Information: This project was supported by in kind contributions from the Observational and Pragmatic Research Institute and the University of Queensland Faculty of Medicine. No pharmaceutical companies were involved in the study design or execution.Conflicts of interest: J.W. Upham reports personal fees from AstraZeneca, GlaxoSmithKline, Sanofi, Boehringer Ingelheim, and Novartis, outside the submitted work. D.J. Jackson reports personal fees from AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Teva, Napp, Chiesi, and Novartis; and grants from AstraZeneca, outside the submitted work. M. Masoli reports personal fees from Novartis and AstraZeneca, outside the submitted work. M.E. Wechsler reports grants and personal fees from Novartis, Sanofi, and Cohero Health; personal fees from Regeneron, Genentech, Sentien, Restorbio, Equillium, and Genzyme; grants, personal fees, and nonfinancial support from Teva and AstraZeneca; personal fees and nonfinancial support from Boehringer Ingelheim; and personal fees from GSK, outside the submitted work. D.B. Price reports grants from AKL Research and Development Ltd, British Lung Foundation, Respiratory Effectiveness Group, and UK National Health Service; grants and personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, Theravance, Zentiva (Sanofi Generics); personal fees from Cipla, GlaxoSmithKline, Kyorin, Merck, Mundipharma, Airway Vista Secretariat, EPG Communication Holdings Ltd, FIECON Ltd, Fieldwork International, OM Pharma SA, PeerVoice, Phadia AB, Spirosure Inc, Strategic North Limited, Synapse Research Management Partners S.L, Talos Health Solutions, and WebMD Global LLC, outside the submitted work; nonfinancial support from Efficacy and Mechanism Evaluation programme and Health Technology Assessment; and stock/stock options from AKL Research and Development Ltd, which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 92.61% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); and 5% shareholding in Timestamp, which develops adherence monitoring technology. The rest of the authors declare that they have no relevant conflicts of interest. Publisher Copyright: © 2021 American Academy of Allergy, Asthma & Immunology

King's Authors

Abstract

Background: Clinicians are increasingly recognizing severe asthma patients in whom biologics and other add-on therapies lead to dramatic improvement. Currently, there is no agreed-upon super-responder (SR) definition. Objective: To survey severe asthma experts using a modified Delphi process, to develop an international consensus-based definition of a severe asthma SR. Methods: The Delphi panel was composed of 81 participants (94% specialist pulmonologists or allergists) from 24 countries and consisted of three iterative online voting rounds. Consensus on individual items, whether acceptance or rejection, required at least 70% agreement by panel members. Results: Consensus was achieved that the SR definition should be based on improvement across three or more domains assessed over 12 months. Major SR criteria included exacerbation elimination, a large improvement in asthma control (two or more times the minimal clinically important difference), and cessation of maintenance of oral steroids (or weaning to adrenal insufficiency). Minor SR criteria were composed of a 75% exacerbation reduction, having well-controlled asthma, and 500 mL or greater improvement in FEV1. The SR definition requires improvement in at least two major criteria. In the future, the SR definition should be expanded to incorporate quality of life measures, although current tools can be difficult to implement in a clinical setting and further research is needed. Conclusions: This international consensus-based definition of severe asthma SRs is an important prerequisite for better understanding SR prevalence, predictive factors, and the mechanisms involved. Further research is needed to understand the patient's perspective and to measure quality of life more precisely in SRs.

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