Biomarker Predictors of Clinical Efficacy of the Anti-IgE Biologic Omalizumab in Severe Asthma in Adults: Results of the SoMOSA Study.

Autor:	Djukanović R; School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton and National Institute for Health and Care Research Southampton Biomedical Research Centre, Southampton, United Kingdom., Brinkman P; Department of Respiratory Medicine, Amsterdam University Medical Center, University of Amsterdam, the Netherlands., Kolmert J; Institute of Environmental Medicine, Karolinska Institutet, and the Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden., Gomez C; Institute of Environmental Medicine, Karolinska Institutet, and the Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden., Schofield J; School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton and National Institute for Health and Care Research Southampton Biomedical Research Centre, Southampton, United Kingdom.; Biological Sciences, University of Southampton, Southampton, United Kingdom., Brandsma J; School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton and National Institute for Health and Care Research Southampton Biomedical Research Centre, Southampton, United Kingdom., Shapanis A; Biological Sciences, University of Southampton, Southampton, United Kingdom., Skipp PJS; School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton and National Institute for Health and Care Research Southampton Biomedical Research Centre, Southampton, United Kingdom.; Biological Sciences, University of Southampton, Southampton, United Kingdom., Postle A; School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton and National Institute for Health and Care Research Southampton Biomedical Research Centre, Southampton, United Kingdom., Wheelock C; Institute of Environmental Medicine, Karolinska Institutet, and the Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden., Dahlen SE; Institute of Environmental Medicine, Karolinska Institutet, and the Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden., Sterk PJ; Department of Respiratory Medicine, Amsterdam University Medical Center, University of Amsterdam, the Netherlands., Brown T; Portsmouth Hospitals University National Health Service Trust, Queen Alexandra Hospital, Portsmouth, United Kingdom., Jackson DJ; Guy's Severe Asthma Centre, School of Immunology & Microbial Sciences, King's College London, London, United Kingdom., Mansur A; University of Birmingham and Heartlands Hospital, University Hospitals Birmingham National Health Service Foundation Trust, Birmingham, United Kingdom., Pavord I; Oxford Respiratory National Institute for Health and Care Research Biomedical Research Centre, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Patel M; Respiratory Medicine and R&D, University Hospitals Plymouth National Health Service Trust, Plymouth, United Kingdom., Brightling C; Institute for Lung Health and Leicester National Institute for Health and Care Research Biomedical Research Centre, University of Leicester, Leicester, United Kingdom., Siddiqui S; Institute for Lung Health and Leicester National Institute for Health and Care Research Biomedical Research Centre, University of Leicester, Leicester, United Kingdom., Bradding P; Institute for Lung Health and Leicester National Institute for Health and Care Research Biomedical Research Centre, University of Leicester, Leicester, United Kingdom., Sabroe I; Clinical Research Facility, Sheffield Teaching Hospitals National Health Service Foundation Trust, Sheffield, United Kingdom., Saralaya D; Bradford Institute for Health Research and the National Patient Recruitment Centre, Bradford, United Kingdom., Chishimba L; Clinical Sciences, Liverpool University Hospitals National Health Service Foundation Trust, Liverpool, United Kingdom., Porter J; University College London Respiratory and National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, London, United Kingdom., Robinson D; University College London Respiratory and National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, London, United Kingdom., Fowler S; Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester, United Kingdom.; Manchester Academic Health Science Centre and National Institute for Health and Care Research Manchester Biomedical Research Centre, Manchester University Hospitals National Health Service Foundation Trust, Manchester, United Kingdom., Howarth PH; School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton and National Institute for Health and Care Research Southampton Biomedical Research Centre, Southampton, United Kingdom., Little L; Southampton Clinical Trials Unit, University of Southampton, and University Hospital Southampton National Health Service Foundation Trust, Southampton, United Kingdom., Oliver T; Southampton Clinical Trials Unit, University of Southampton, and University Hospital Southampton National Health Service Foundation Trust, Southampton, United Kingdom., Hill K; Southampton Clinical Trials Unit, University of Southampton, and University Hospital Southampton National Health Service Foundation Trust, Southampton, United Kingdom., Stanton L; Southampton Clinical Trials Unit, University of Southampton, and University Hospital Southampton National Health Service Foundation Trust, Southampton, United Kingdom., Allen A; Southampton Clinical Trials Unit, University of Southampton, and University Hospital Southampton National Health Service Foundation Trust, Southampton, United Kingdom., Ellis D; Southampton Clinical Trials Unit, University of Southampton, and University Hospital Southampton National Health Service Foundation Trust, Southampton, United Kingdom., Griffiths G; Southampton Clinical Trials Unit, University of Southampton, and University Hospital Southampton National Health Service Foundation Trust, Southampton, United Kingdom., Harrison T; Nottingham Respiratory National Institute for Health and Care Research Biomedical Research Centre, University of Nottingham, Nottingham, United Kingdom., Akenroye A; Division of Allergy and Clinical Immunology and.; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts., Lasky-Su J; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts., Heaney L; Wellcome-Wolfson Institute for Experimental Medicine, Belfast, Northern Ireland; and., Chaudhuri R; Gartnavel General Hospital and School of Infection & Immunity, University of Glasgow, Glasgow, United Kingdom., Kurukulaaratchy R; School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton and National Institute for Health and Care Research Southampton Biomedical Research Centre, Southampton, United Kingdom.
Jazyk:	angličtina
Zdroj:	American journal of respiratory and critical care medicine [Am J Respir Crit Care Med] 2024 Aug 01; Vol. 210 (3), pp. 288-297.
DOI:	10.1164/rccm.202310-1730OC
Abstrakt:	Background: The anti-IgE monoclonal antibody omalizumab is widely used for severe asthma. This study aimed to identify biomarkers that predict clinical improvement during 1 year of omalizumab treatment. Methods: One-year open-label Study of Mechanisms of action of Omalizumab in Severe Asthma (SoMOSA) involving 216 patients with severe (Global Initiative for Asthma step 4/5) uncontrolled atopic asthma (at least two severe exacerbations in the previous year) taking high-dose inhaled corticosteroids and long-acting β-agonists with or without maintenance oral corticosteroids. It had two phases: 0-16 weeks, to assess early clinical improvement by Global Evaluation of Therapeutic Effectiveness (GETE); and 16-52 weeks, to assess late responses based on ⩾50% reduction in exacerbations or mOCS dose. All participants provided samples (exhaled breath, blood, sputum, urine) before and after 16 weeks of omalizumab treatment. Measurements and Main Results: A total of 191 patients completed phase 1; 63% had early improvement. Of 173 who completed phase 2, 69% had reduced exacerbations by ⩾50% and 57% (37 of 65) taking mOCSs had reduced their dose by ⩾50%. The primary outcomes 2,3-dinor-11-β-PGF2α, GETE score, and standard clinical biomarkers (blood and sputum eosinophils, exhaled nitric oxide, serum IgE) did not predict either clinical response. Five volatile organic compounds and five plasma lipid biomarkers strongly predicted the ⩾50% reduction in exacerbations (receiver operating characteristic areas under the curve of 0.780 and 0.922, respectively) and early responses (areas under the curve of 0.835 and 0.949, respectively). In an independent cohort, gas chromatography/mass spectrometry biomarkers differentiated between severe and mild asthma. Conclusions: This is the first discovery of omics biomarkers that predict improvement in asthma with biologic agent treatment. Prospective validation and development for clinical use is justified.
Databáze:	MEDLINE
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