Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma
(2024) In Frontiers in Immunology 15.- Abstract
- Background: To date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials. Aim: To elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life. Methods: This was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to... (More)
- Background: To date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials. Aim: To elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life. Methods: This was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers. Results: Overall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher pre-biologic BEC and FeNO were both associated with greater post-biologic improvement in FEV1 for both anti-IgE and anti-IL5/5R, with a trend for anti-IL4Rα. Mean FEV1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/µL), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and -anti-IL4Rα, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4Rα, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.392; p=0.001) post-biologic for anti-IL5/5R. Pre-biologic IgE was a poor predictor of subsequent pre-to-post-biologic change for all outcomes assessed for all biologics. The combination of BEC + FeNO marginally improved the prediction of post-biologic FEV1 increase (adjusted R2: 0.751), compared to BEC (adjusted R2: 0.747) or FeNO alone (adjusted R2: 0.743) (p=0.005 and (Less)
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https://lup.lub.lu.se/record/21ec4227-57fe-4d9a-aefa-ed6be3acbf69
- author
- Porsbjerg, C.M. ; Bjermer, L. LU and Price, D.B.
- author collaboration
- organization
- publishing date
- 2024
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- biologics, biomarkers, eosinophil (EOS), FeNO (Fraction of exhaled Nitric Oxide), FEV1, personalized medicine (PM), severe asthma
- in
- Frontiers in Immunology
- volume
- 15
- article number
- 1361891
- publisher
- Frontiers Media S. A.
- external identifiers
-
- scopus:85192184245
- pmid:38711495
- ISSN
- 1664-3224
- DOI
- 10.3389/fimmu.2024.1361891
- language
- English
- LU publication?
- yes
- id
- 21ec4227-57fe-4d9a-aefa-ed6be3acbf69
- date added to LUP
- 2024-05-14 11:30:01
- date last changed
- 2024-05-15 11:00:20
@article{21ec4227-57fe-4d9a-aefa-ed6be3acbf69, abstract = {{Background: To date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials. Aim: To elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life. Methods: This was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers. Results: Overall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher pre-biologic BEC and FeNO were both associated with greater post-biologic improvement in FEV1 for both anti-IgE and anti-IL5/5R, with a trend for anti-IL4Rα. Mean FEV1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/µL), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and -anti-IL4Rα, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4Rα, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.392; p=0.001) post-biologic for anti-IL5/5R. Pre-biologic IgE was a poor predictor of subsequent pre-to-post-biologic change for all outcomes assessed for all biologics. The combination of BEC + FeNO marginally improved the prediction of post-biologic FEV1 increase (adjusted R2: 0.751), compared to BEC (adjusted R2: 0.747) or FeNO alone (adjusted R2: 0.743) (p=0.005 and}}, author = {{Porsbjerg, C.M. and Bjermer, L. and Price, D.B.}}, issn = {{1664-3224}}, keywords = {{biologics; biomarkers; eosinophil (EOS); FeNO (Fraction of exhaled Nitric Oxide); FEV1; personalized medicine (PM); severe asthma}}, language = {{eng}}, publisher = {{Frontiers Media S. A.}}, series = {{Frontiers in Immunology}}, title = {{Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma}}, url = {{http://dx.doi.org/10.3389/fimmu.2024.1361891}}, doi = {{10.3389/fimmu.2024.1361891}}, volume = {{15}}, year = {{2024}}, }