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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.

Abstract
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.
Author
Djukanović, Ratko
Brinkman, Paul
Kolmert, Johan
Gomez, Cristina
Schofield, James
Brandsma, Joost
Shapanis, Andy
Skipp, Paul J S
Postle, Anthony
Wheelock, Craig
Dahlén, Sven-Erik
Sterk, Peter J
Brown, Thomas
Jackson, David J
Mansur, Adel
Pavord, Ian
Patel, Mitesh
Brightling, Christopher
Siddiqui, Salman
Bradding, Peter
Sabroe, Ian
Saralaya, Dinesh
Chishimba, Livingstone
Porter, Joanna
Robinson, Douglas
Fowler, Stephen J
Howarth, Peter H
Little, Louisa
Oliver, Thomas
Hill, Kayleigh
Stanton, Louise
Allen, Alexander
Ellis, Deborah
Griffiths, Gareth
Harrison, Tim
Akenroye, Ayobami
Lasky-Su, Jessica
Heaney, Liam
Chaudhuri, Rekha
Kurukulaaratchy, Ramesh
Citations
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Date
2024-04-18
Type
Article
Subject
Respiratory medicine
Collections
UHB Respiratory
Evidence Summaries
Evidence Summaries
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Citation
Djukanović R, Brinkman P, Kolmert J, Gomez C, Schofield J, Brandsma J, Shapanis A, Skipp PJS, Postle A, Wheelock C, Dahlén SE, Sterk PJ, Brown T, Jackson DJ, Mansur A, Pavord I, Patel M, Brightling C, Siddiqui S, Bradding P, Sabroe I, Saralaya D, Chishimba L, Porter J, Robinson D, Fowler SJ, Howarth PH, Little L, Oliver T, Hill K, Stanton L, Allen A, Ellis D, Griffiths G, Harrison T, Akenroye A, Lasky-Su J, Heaney L, Chaudhuri R, Kurukulaaratchy R. Biomarker Predictors of Clinical Efficacy of the Anti-IgE Biologic, Omalizumab, in Severe Asthma in Adults: Results of the SoMOSA Study. Am J Respir Crit Care Med. 2024 Apr 18. doi: 10.1164/rccm.202310-1730OC.
Journal / Source Title
American Journal of Respiratory and Critical Care Medicine
DOI
10.1164/rccm.202310-1730OC
URI
http://hdl.handle.net/20.500.14200/4704
PMID
38635834
Publisher
American Thoracic Society
Publisher’s URL
https://www.atsjournals.org/journal/ajrccm
Publisher’s statement
Note / Copyright