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

2024; American Thoracic Society; Volume: 210; Issue: 3 Linguagem: Inglês

10.1164/rccm.202310-1730oc

1535-4970

Ratko Djukanović, Paul Brinkman, Johan Kolmert, Cristina Gómez, James Schofield, Joost Brandsma, Andy Shapanis, Paul Skipp, Anthony D. Postle, Craig E. Wheelock, Barbro Dahlén, Peter J. Sterk, Thomas Brown, David J. Jackson, Adel Mansur, Ian Pavord, Mitesh Patel, Christopher E. Brightling, Salman Siddiqui, Peter Bradding, Ian Sabroe, Dinesh Saralaya, Livingstone Chishimba, Joanna C. Porter, Douglas S. Robinson, Stephen J. Fowler, Peter Howarth, Louisa Little, Thomas Oliver, Kayleigh Hill, Louise Stanton, Allen Alexander, Deborah A. Ellis, Gareth Griffiths, Tim Harrison, Ayobami Akenroye, Jessica Lasky‐Su, Liam G. Heaney, Rekha Chaudhuri, Ramesh Kurukulaaratchy, Ratko Djukanović, Anthony D. Postle, Craig E. Wheelock, Peter J. Sterk, Paul Skipp, Gareth Griffiths, Louisa Little, Borislav D. Dimitrov, Liam G. Heaney, Rekha Chaudhuri, Peter Bradding, Ratko Djukanović, Liam G. Heaney, Rekha Chaudhuri, Tim Harrison, Robert Niven, Tom Stokes, Thomas Oliver, Rekha Chaudhuri, Robin Gore, Liam G. Heaney, Adel Mansur, Dinesh Saralaya, Ian Pavord, Mitesh Patel, Christopher E. Brightling, David J. Jackson, Tim Harrison, Thomas Brown, Ian Sabroe, Livingstone Chishimba, Ramesh Kurukulaaratchy, Joanna C. Porter, Stephen J. Fowler, Vanessa Brown, Alison Clinton, Christine McAnally, Rahul Shrimanker, Gareth Hynes, Mary Green, Salman Siddiqui, Peter Bradding, Christobelle White, Richard Russell, Michelle Bourne, Beverley Hargadon, Vijay Mistry, Tracey Thornton, Sarah Diver, Joanne Kavanagh, Diana Roque, Brittan A. Durham, Linda J. Kay, Matthew Austin, A. Ian Smith, Mercy Korley, Steven W. Anderson, Lynn Haslam‐Larmer, Katherine Smith, Helen Smith, Christopher J. Brereton, Kamran Tariq, Laura Presland, Clair Barber, Jonathan Ward, Jagdeep Sahota, Joel Solis, Akif A. Khawaja, Valarie Magaya, Sarah Davies, Mary Bellamy, Lesley Horton, Tamika Thompson, Jacqui Galloway, Tom Dymond, Matthew Masoli, J. L. Anderton, Natasha Wilmhurst, Jack Kingdon, Thomas W. Jones, Jonathon Winter, Scott Elliott, Daniela M. Ferreira, Jesús Reiné Esther, John Blakey, Elena Mitsi, Carla Solórzano, Elissavet Nikolaou, Catherine Lowe, Freda Yang, Steven Smith, Diane Murray, Tracyanne Grandison, Marc Jones, Gareth Griffiths, Thomas Oliver, Louisa Little, Jessica Rajaram, Nicholas Das, Zina Eminton, Jacqui Nuttall, Susi Renz, C.D. Forbes, Allen Alexander, Deborah A. Ellis, Emma Tilt, Emma Wrixon, Nicola Scott, Kayleigh Hill, Kerensa Thorne, Angeliki Galanopolous, Louise Stanton, Paul Brinkman, James Schofield, Johan Kolmert, Joost Brandsma, Gareth J Griffith, Ratko Djukanović, Borislav D. Dimitrov, Ayobami Akenroye, Jessica Lasky‐Su, Kathryn Clark, Keira Fines, Benjamin Sale,

Pharmacological Effects and Assays

Background: The anti-IgE monoclonal, omalizumab, is widely used for severe asthma. This study aimed to identify biomarkers that predict clinical improvement during one year of omalizumab treatment. Methods: 1-year, open-label, Study of Mechanisms of action of Omalizumab in Severe Asthma (SoMOSA) involving 216 severe (GINA step 4/5) uncontrolled atopic asthmatics (≥2 severe exacerbations in previous year) on high-dose inhaled corticosteroids, long-acting β-agonists, ± mOCS. 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 by ≥50% reduction in exacerbations or dose of maintenance oral corticosteroids (mOCS). All participants provided samples (exhaled breath, blood, sputum, urine) before and after 16 weeks of omalizumab treatment. Results: 191 patients completed phase 1; 63% had early improvement. Of 173 who completed phase 2, 69% had reduced exacerbations by ≥50%, while 57% (37/65) on mOCS reduced their dose by ≥50%. The primary outcome 2, 3-dinor-11-β-PGF2α, GETE and standard clinical biomarkers (blood and sputum eosinophils, exhaled nitric oxide, serum IgE) did not predict either clinical response. Five breathomics (GC-MS) and 5 plasma lipid biomarkers strongly predicted the ≥50% reduction in exacerbations (receiver operating characteristic area under the curve (AUC): 0.780 and 0.922, respectively) and early responses (AUC:0.835 and 0.949, respectively). In independent cohorts, the GC-MS biomarkers differentiated between severe and mild asthma. Conclusions This is the first discovery of omics biomarkers that predict improvement to a biologic for asthma. Their prospective validation and development for clinical use is justified.