• Ratko Djukanović, Paul Brinkman, Johan Kolmert, Cristina Gomez, James Schofield, Joost Brandsma, Andy Shapanis, Paul J S Skipp, Anthony Postle, Craig Wheelock, Sven-Erik Dahlen, Peter J Sterk, Thomas Brown, David J Jackson, Adel Mansur, Ian Pavord, Mitesh Patel, Christopher Brightling, Salman Siddiqui, Peter Bradding, Ian Sabroe, Dinesh Saralaya, Livingstone Chishimba, Joanna Porter, Douglas Robinson, Stephen Fowler, Peter H Howarth, Louisa Little, Thomas Oliver, Kayleigh Hill, Louise Stanton, Alexander Allen, Deborah Ellis, Gareth Griffiths, Tim Harrison, Ayobami Akenroye, Jessica Lasky-Su, Liam Heaney, Rekha Chaudhuri, Ramesh Kurukulaaratchy, and SoMOSA study team and the U-BIOPRED study team.
• 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.
• Am. J. Respir. Crit. Care Med. 2024 Aug 1; 210 (3): 288297288-297.

AbstractBackground: 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.

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