Biomarker Predictors of Clinical Efficacy of the Anti-IgE Biologic Omalizumab in Severe Asthma in Adults: Results of the SoMOSA Study
Authors: 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, Ratko Djukanović, Anthony Postle, Craig Wheelock, Peter J. Sterk, Paul Skipp, Gareth Griffiths, Louisa Little, Borislav Dimitrov, Liam Heaney, Rekha Chaudhuri, Peter Bradding, Ratko Djukanović, Liam Heaney, Rekha Chaudhuri, Tim Harrison, Robert Niven, Tom Stokes, Thomas Oliver, Rekha Chaudhuri, Robin Gore, Liam Heaney, Adel Mansur, Dinesh Saralaya, Ian Pavord, Mitesh Patel, Christopher Brightling, David Jackson, Tim Harrison, Thomas Brown, Ian Sabroe, Livingstone Chishimba, Ramesh Kurukulaaratchy, Joanna Porter, Stephen 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, Ben Durham, Linda Kay, Matthew Austin, Ian Smith, Mercy Korley, Sam Anderson, Liam Haslam, Katherine Smith, Helen Smith, Christopher Brereton, Kamran Tariq, Laura Presland, Clair Barber, Jon Ward, Jagdeep Sahota, Joel Solis, Akif Khawaja, Valarie Magaya, Sarah Davies, Mary Bellamy, Lesley Horton, Tamika Thompson, Jacqui Galloway, Tom Dymond, Matthew Masoli, Julie Anderton, Natasha Wilmhurst, Jennifer Kingdon, Thomas Jones, Jonathon Winter, Scott Elliott, Daniela Ferreira, Jesús Reiné Esther, John Blakey, Elena Mitsi, Carla Solorzano, 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, Claire Forbes, Alexander Allen, Deborah Ellis, Emma Tilt, Emma Wrixon, Nicola Scott, Kayleigh Hill, Kerensa Thorne, Angeliki Galanopolous, Louise Stanton, Paul Brinkman, James Schofield, Johan Kolmert, Joost Brandsma, Gareth Griffith, Ratko Djukanović, Borislav Dimitrov, Ayobami Akenroye, Jessica Lasky-Su, Kathryn Clark, Keira Fines, Benjamin Sale
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

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.