%0 Journal Article
%A Porsbjerg, Celeste M
%A Townend, John
%A Bergeron, Celine
%A Christoff, George C
%A Katsoulotos, Gregory P
%A Larenas-Linnemann, Désirée
%A Tran, Trung N
%A Al-Lehebi, Riyad
%A Bosnic-Anticevich, Sinthia Z
%A Busby, John
%A Hew, Mark
%A Kostikas, Konstantinos
%A Papadopoulos, Nikolaos G
%A Pfeffer, Paul E
%A Popov, Todor A
%A Rhee, Chin Kook
%A Sadatsafavi, Mohsen
%A Tsai, Ming-Ju
%A Ulrik, Charlotte Suppli
%A Al-Ahmad, Mona
%A Altraja, Alan
%A Beastall, Aaron
%A Bulathsinhala, Lakmini
%A Carter, Victoria
%A García-Cosío, Borja 
%A Fletton, Kirsty
%A Hansen, Susanne
%A Heaney, Liam G
%A Hubbard, Richard B
%A Kuna, Piotr
%A Murray, Ruth B
%A Nagano, Tatsuya
%A Pini, Laura
%A Cano Rosales, Diana Jimena
%A Schleich, Florence
%A Wechsler, Michael E
%A Amaral, Rita
%A Bourdin, Arnaud
%A Brusselle, Guy G.
%A Chen, Wenjia
%A Chung, Li Ping
%A Denton, Eve
%A Fonseca, Joao A
%A Hoyte, Flavia
%A Jackson, David J
%A Katial, Rohit
%A Kirenga, Bruce J
%A Koh, Mariko Siyue
%A Ławkiedraj, Agnieszka
%A Lehtimäki, Lauri
%A Liew, Mei Fong
%A Mahboub, Bassam
%A Martin, Neil
%A Menzies-Gow, Andrew N
%A Pang, Pee Hwee
%A Papaioannou, Andriana I
%A Patel, Pujan H
%A Perez-De-Llano, Luis
%A Peters, Matthew J
%A Ricciardi, Luisa
%A Rodríguez-Cáceres, Bellanid
%A Solarte, Ivan
%A Tay, Tunn Ren
%A Torres-Duque, Carlos A
%A Wang, Eileen
%A Zappa, Martina
%A Abisheganaden, John
%A Assing, Karin Dahl
%A Costello, Richard W.
%A Gibson, Peter G
%A Heffler, Enrico
%A Máspero, Jorge
%A Nicola, Stefania
%A Perng Steve, Diahn-Warng
%A Puggioni, Francesca
%A Salvi, Sundeep
%A Sheu, Chau-Chyun
%A Sirena, Concetta
%A Taillé, Camille
%A Tan, Tze Lee
%A Bjermer, Leif
%A Canonica, Giorgio Walter
%A Iwanaga, Takashi
%A Jiménez-Maldonado, Libardo
%A Taube, Christian
%A Brussino, Luisa
%A Price, David B
%T Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma
%D 2024
%U https://hdl.handle.net/20.500.13003/20337
%X 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.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.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.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.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.
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