RT Journal Article
T1 Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma
A1 Porsbjerg, Celeste M
A1 Townend, John
A1 Bergeron, Celine
A1 Christoff, George C
A1 Katsoulotos, Gregory P
A1 Larenas-Linnemann, Désirée
A1 Tran, Trung N
A1 Al-Lehebi, Riyad
A1 Bosnic-Anticevich, Sinthia Z
A1 Busby, John
A1 Hew, Mark
A1 Kostikas, Konstantinos
A1 Papadopoulos, Nikolaos G
A1 Pfeffer, Paul E
A1 Popov, Todor A
A1 Rhee, Chin Kook
A1 Sadatsafavi, Mohsen
A1 Tsai, Ming-Ju
A1 Ulrik, Charlotte Suppli
A1 Al-Ahmad, Mona
A1 Altraja, Alan
A1 Beastall, Aaron
A1 Bulathsinhala, Lakmini
A1 Carter, Victoria
A1 García-Cosío, Borja
A1 Fletton, Kirsty
A1 Hansen, Susanne
A1 Heaney, Liam G
A1 Hubbard, Richard B
A1 Kuna, Piotr
A1 Murray, Ruth B
A1 Nagano, Tatsuya
A1 Pini, Laura
A1 Cano Rosales, Diana Jimena
A1 Schleich, Florence
A1 Wechsler, Michael E
A1 Amaral, Rita
A1 Bourdin, Arnaud
A1 Brusselle, Guy G.
A1 Chen, Wenjia
A1 Chung, Li Ping
A1 Denton, Eve
A1 Fonseca, Joao A
A1 Hoyte, Flavia
A1 Jackson, David J
A1 Katial, Rohit
A1 Kirenga, Bruce J
A1 Koh, Mariko Siyue
A1 Ławkiedraj, Agnieszka
A1 Lehtimäki, Lauri
A1 Liew, Mei Fong
A1 Mahboub, Bassam
A1 Martin, Neil
A1 Menzies-Gow, Andrew N
A1 Pang, Pee Hwee
A1 Papaioannou, Andriana I
A1 Patel, Pujan H
A1 Perez-De-Llano, Luis
A1 Peters, Matthew J
A1 Ricciardi, Luisa
A1 Rodríguez-Cáceres, Bellanid
A1 Solarte, Ivan
A1 Tay, Tunn Ren
A1 Torres-Duque, Carlos A
A1 Wang, Eileen
A1 Zappa, Martina
A1 Abisheganaden, John
A1 Assing, Karin Dahl
A1 Costello, Richard W.
A1 Gibson, Peter G
A1 Heffler, Enrico
A1 Máspero, Jorge
A1 Nicola, Stefania
A1 Perng Steve, Diahn-Warng
A1 Puggioni, Francesca
A1 Salvi, Sundeep
A1 Sheu, Chau-Chyun
A1 Sirena, Concetta
A1 Taillé, Camille
A1 Tan, Tze Lee
A1 Bjermer, Leif
A1 Canonica, Giorgio Walter
A1 Iwanaga, Takashi
A1 Jiménez-Maldonado, Libardo
A1 Taube, Christian
A1 Brussino, Luisa
A1 Price, David B
AB 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.
PB Frontiers
YR 2024
FD 2024
LK https://hdl.handle.net/20.500.13003/20337
UL https://hdl.handle.net/20.500.13003/20337
LA eng
NO Porsbjerg CM, Townend J, Bergeron C, Christoff GC, Katsoulotos GP, Larenas-Linnemann D, et al. Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma. Front Immunol. 2024 Apr 19;15.
DS Docusalut
RD 31 jul. 2026