@article{20.500.13003/20337,
year = {2024},
url = {https://hdl.handle.net/20.500.13003/20337},
abstract = {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.},
publisher = {Frontiers},
title = {Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma},
doi = {10.3389/fimmu.2024.1361891},
journal = {Frontiers in immunology},
volume = {15},
author = {Porsbjerg, Celeste M and Townend, John and Bergeron, Celine and Christoff, George C and Katsoulotos, Gregory P and Larenas-Linnemann, Désirée and Tran, Trung N and Al-Lehebi, Riyad and Bosnic-Anticevich, Sinthia Z and Busby, John and Hew, Mark and Kostikas, Konstantinos and Papadopoulos, Nikolaos G and Pfeffer, Paul E and Popov, Todor A and Rhee, Chin Kook and Sadatsafavi, Mohsen and Tsai, Ming-Ju and Ulrik, Charlotte Suppli and Al-Ahmad, Mona and Altraja, Alan and Beastall, Aaron and Bulathsinhala, Lakmini and Carter, Victoria and García-Cosío, Borja  and Fletton, Kirsty and Hansen, Susanne and Heaney, Liam G and Hubbard, Richard B and Kuna, Piotr and Murray, Ruth B and Nagano, Tatsuya and Pini, Laura and Cano Rosales, Diana Jimena and Schleich, Florence and Wechsler, Michael E and Amaral, Rita and Bourdin, Arnaud and Brusselle, Guy G.
 and Chen, Wenjia and Chung, Li Ping and Denton, Eve and Fonseca, Joao A and Hoyte, Flavia and Jackson, David J and Katial, Rohit and Kirenga, Bruce J and Koh, Mariko Siyue and Ławkiedraj, Agnieszka and Lehtimäki, Lauri and Liew, Mei Fong and Mahboub, Bassam and Martin, Neil and Menzies-Gow, Andrew N and Pang, Pee Hwee and Papaioannou, Andriana I and Patel, Pujan H and Perez-De-Llano, Luis and Peters, Matthew J and Ricciardi, Luisa and Rodríguez-Cáceres, Bellanid and Solarte, Ivan and Tay, Tunn Ren and Torres-Duque, Carlos A and Wang, Eileen and Zappa, Martina and Abisheganaden, John and Assing, Karin Dahl and Costello, Richard W. and Gibson, Peter G and Heffler, Enrico and Máspero, Jorge and Nicola, Stefania and Perng Steve, Diahn-Warng and Puggioni, Francesca and Salvi, Sundeep and Sheu, Chau-Chyun and Sirena, Concetta and Taillé, Camille and Tan, Tze Lee and Bjermer, Leif and Canonica, Giorgio Walter and Iwanaga, Takashi and Jiménez-Maldonado, Libardo and Taube, Christian and Brussino, Luisa and Price, David B},
}