TY - JOUR
T1 - Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma
AU - Porsbjerg, Celeste M.
AU - Townend, John
AU - Bergeron, Celine
AU - Christoff, George C.
AU - Katsoulotos, Gregory P.
AU - Larenas-Linnemann, Désirée
AU - Tran, Trung N.
AU - Al-Lehebi, Riyad
AU - Bosnic-Anticevich, Sinthia Z.
AU - Busby, John
AU - Hew, Mark
AU - Kostikas, Konstantinos
AU - Papadopoulos, Nikolaos G.
AU - Pfeffer, Paul E.
AU - Popov, Todor A.
AU - Rhee, Chin Kook
AU - Sadatsafavi, Mohsen
AU - Tsai, Ming Ju
AU - Ulrik, Charlotte Suppli
AU - Al-Ahmad, Mona
AU - Altraja, Alan
AU - Beastall, Aaron
AU - Bulathsinhala, Lakmini
AU - Carter, Victoria
AU - Cosio, Borja G.
AU - Fletton, Kirsty
AU - Hansen, Susanne
AU - Heaney, Liam G.
AU - Hubbard, Richard B.
AU - Kuna, Piotr
AU - Murray, Ruth B.
AU - Nagano, Tatsuya
AU - Pini, Laura
AU - Cano Rosales, Diana Jimena
AU - Schleich, Florence
AU - Wechsler, Michael E.
AU - Amaral, Rita
AU - Bourdin, Arnaud
AU - Brusselle, Guy G.
AU - Chen, Wenjia
AU - Chung, Li Ping
AU - Denton, Eve
AU - Fonseca, Joao A.
AU - Hoyte, Flavia
AU - Jackson, David J.
AU - Katial, Rohit
AU - Kirenga, Bruce J.
AU - Koh, Mariko Siyue
AU - Ławkiedraj, Agnieszka
AU - Lehtimäki, Lauri
AU - Liew, Mei Fong
AU - Mahboub, Bassam
AU - Martin, Neil
AU - Menzies-Gow, Andrew N.
AU - Pang, Pee Hwee
AU - Papaioannou, Andriana I.
AU - Patel, Pujan H.
AU - Perez-De-Llano, Luis
AU - Peters, Matthew J.
AU - Ricciardi, Luisa
AU - Rodríguez-Cáceres, Bellanid
AU - Solarte, Ivan
AU - Tay, Tunn Ren
AU - Torres-Duque, Carlos A.
AU - Wang, Eileen
AU - Zappa, Martina
AU - Abisheganaden, John
AU - Assing, Karin Dahl
AU - Costello, Richard W.
AU - Gibson, Peter G.
AU - Heffler, Enrico
AU - Máspero, Jorge
AU - Nicola, Stefania
AU - Perng, Diahn Warng
AU - Puggioni, Francesca
AU - Salvi, Sundeep
AU - Sheu, Chau Chyun
AU - Sirena, Concetta
AU - Taillé, Camille
AU - Tan, Tze Lee
AU - Bjermer, Leif
AU - Canonica, Giorgio Walter
AU - Iwanaga, Takashi
AU - Jiménez-Maldonado, Libardo
AU - Taube, Christian
AU - Brussino, Luisa
AU - Price, David B.
N1 - Publisher Copyright:
Copyright © 2024 Porsbjerg, Townend, Bergeron, Christoff, Katsoulotos, Larenas-Linnemann, Tran, Al-Lehebi, Bosnic-Anticevich, Busby, Hew, Kostikas, Papadopoulos, Pfeffer, Popov, Rhee, Sadatsafavi, Tsai, Ulrik, Al-Ahmad, Altraja, Beastall, Bulathsinhala, Carter, Cosio, Fletton, Hansen, Heaney, Hubbard, Kuna, Murray, Nagano, Pini, Cano Rosales, Schleich, Wechsler, Amaral, Bourdin, Brusselle, Chen, Chung, Denton, Fonseca, Hoyte, Jackson, Katial, Kirenga, Koh, Ławkiedraj, Lehtimäki, Liew, Mahboub, Martin, Menzies-Gow, Pang, Papaioannou, Patel, Perez-De-Llano, Peters, Ricciardi, Rodríguez-Cáceres, Solarte, Tay, Torres-Duque, Wang, Zappa, Abisheganaden, Assing, Costello, Gibson, Heffler, Máspero, Nicola, Perng (Steve), Puggioni, Salvi, Sheu, Sirena, Taillé, Tan, Bjermer, Canonica, Iwanaga, Jiménez-Maldonado, Taube, Brussino and Price.
PY - 2024
Y1 - 2024
N2 - 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 <0.001, respectively); however, this prediction was not improved by the addition of IgE. Conclusions: The ability of higher baseline BEC, FeNO and their combination to predict biologic-associated lung function improvement may encourage earlier intervention in patients with impaired lung function or at risk of accelerated lung function decline.
AB - 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 <0.001, respectively); however, this prediction was not improved by the addition of IgE. Conclusions: The ability of higher baseline BEC, FeNO and their combination to predict biologic-associated lung function improvement may encourage earlier intervention in patients with impaired lung function or at risk of accelerated lung function decline.
KW - FEV1
KW - FeNO (Fraction of exhaled Nitric Oxide)
KW - biologics
KW - biomarkers
KW - eosinophil (EOS)
KW - personalized medicine (PM)
KW - severe asthma
UR - http://www.scopus.com/inward/record.url?scp=85192184245&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2024.1361891
DO - 10.3389/fimmu.2024.1361891
M3 - Article
C2 - 38711495
AN - SCOPUS:85192184245
SN - 1664-3224
VL - 15
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 1361891
ER -