Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma
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 biomar...
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| Формат: | Journal Article |
| Язык: | English |
| Опубликовано: |
2024
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| Online-ссылка: | https://hdl.handle.net/10356/179929 |
| _version_ | 1826121250991243264 |
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| author | Porsbjerg, Celeste M. Townend, John Bergeron, Celine Christoff, George C. Katsoulotos, Gregory P. Larenas-Linnemann, Désirée Tran, Trung N. Al-Lehebi, Riyad Bosnic-Anticevich, Sinthia Z. Busby, John Hew, Mark Kostikas, Konstantinos Papadopoulos, Nikolaos G. Pfeffer, Paul E. Popov, Todor A. Rhee, Chin Kook Sadatsafavi, Mohsen Tsai, Ming-Ju Ulrik, Charlotte Suppli Al-Ahmad, Mona Altraja, Alan Beastall, Aaron Bulathsinhala, Lakmini Carter, Victoria Cosio, Borja G. Fletton, Kirsty Hansen, Susanne Heaney, Liam G. Hubbard, Richard B. Kuna, Piotr Murray, Ruth B. Nagano, Tatsuya Pini, Laura Rosales, Diana Jimena Cano Schleich, Florence Wechsler, Michael E. Amaral, Rita Bourdin, Arnaud Brusselle, Guy G. Chen, Wenjia Chung, Li Ping Denton, Eve Fonseca, Joao A. Hoyte, Flavia Jackson, David J. Katial, Rohit Kirenga, Bruce J. Koh, Mariko Siyue Ławkiedraj, Agnieszka Lehtimäki, Lauri Liew, Mei Fong Mahboub, Bassam Martin, Neil Menzies-Gow, Andrew N. Pang, Pee Hwee Papaioannou, Andriana I. Patel, Pujan H. Perez-De-Llano, Luis Peters, Matthew J. Ricciardi, Luisa Rodríguez-Cáceres, Bellanid Solarte, Ivan Tay, Tunn Ren Torres-Duque, Carlos A. Wang, Eileen Zappa, Martina Abisheganaden, John Assing, Karin Dahl Costello, Richard W. Gibson, Peter G. Heffler, Enrico Máspero, Jorge Nicola, Stefania Perng, Diahn-Warng Steve Puggioni, Francesca Salvi, Sundeep Sheu, Chau-Chyun Sirena, Concetta Taillé, Camille Tan, Tze Lee Bjermer, Leif Canonica, Giorgio Walter Iwanaga, Takashi Jiménez-Maldonado, Libardo Taube, Christian Brussino, Luisa Price, David B. |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Porsbjerg, Celeste M. Townend, John Bergeron, Celine Christoff, George C. Katsoulotos, Gregory P. Larenas-Linnemann, Désirée Tran, Trung N. Al-Lehebi, Riyad Bosnic-Anticevich, Sinthia Z. Busby, John Hew, Mark Kostikas, Konstantinos Papadopoulos, Nikolaos G. Pfeffer, Paul E. Popov, Todor A. Rhee, Chin Kook Sadatsafavi, Mohsen Tsai, Ming-Ju Ulrik, Charlotte Suppli Al-Ahmad, Mona Altraja, Alan Beastall, Aaron Bulathsinhala, Lakmini Carter, Victoria Cosio, Borja G. Fletton, Kirsty Hansen, Susanne Heaney, Liam G. Hubbard, Richard B. Kuna, Piotr Murray, Ruth B. Nagano, Tatsuya Pini, Laura Rosales, Diana Jimena Cano Schleich, Florence Wechsler, Michael E. Amaral, Rita Bourdin, Arnaud Brusselle, Guy G. Chen, Wenjia Chung, Li Ping Denton, Eve Fonseca, Joao A. Hoyte, Flavia Jackson, David J. Katial, Rohit Kirenga, Bruce J. Koh, Mariko Siyue Ławkiedraj, Agnieszka Lehtimäki, Lauri Liew, Mei Fong Mahboub, Bassam Martin, Neil Menzies-Gow, Andrew N. Pang, Pee Hwee Papaioannou, Andriana I. Patel, Pujan H. Perez-De-Llano, Luis Peters, Matthew J. Ricciardi, Luisa Rodríguez-Cáceres, Bellanid Solarte, Ivan Tay, Tunn Ren Torres-Duque, Carlos A. Wang, Eileen Zappa, Martina Abisheganaden, John Assing, Karin Dahl Costello, Richard W. Gibson, Peter G. Heffler, Enrico Máspero, Jorge Nicola, Stefania Perng, Diahn-Warng Steve Puggioni, Francesca Salvi, Sundeep Sheu, Chau-Chyun Sirena, Concetta Taillé, Camille Tan, Tze Lee Bjermer, Leif Canonica, Giorgio Walter Iwanaga, Takashi Jiménez-Maldonado, Libardo Taube, Christian Brussino, Luisa Price, David B. |
| author_sort | Porsbjerg, Celeste M. |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T05:29:38Z |
| format | Journal Article |
| id | ntu-10356/179929 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:29:38Z |
| publishDate | 2024 |
| record_format | dspace |
| spelling | ntu-10356/1799292024-09-08T15:38:14Z Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma Porsbjerg, Celeste M. Townend, John Bergeron, Celine Christoff, George C. Katsoulotos, Gregory P. Larenas-Linnemann, Désirée Tran, Trung N. Al-Lehebi, Riyad Bosnic-Anticevich, Sinthia Z. Busby, John Hew, Mark Kostikas, Konstantinos Papadopoulos, Nikolaos G. Pfeffer, Paul E. Popov, Todor A. Rhee, Chin Kook Sadatsafavi, Mohsen Tsai, Ming-Ju Ulrik, Charlotte Suppli Al-Ahmad, Mona Altraja, Alan Beastall, Aaron Bulathsinhala, Lakmini Carter, Victoria Cosio, Borja G. Fletton, Kirsty Hansen, Susanne Heaney, Liam G. Hubbard, Richard B. Kuna, Piotr Murray, Ruth B. Nagano, Tatsuya Pini, Laura Rosales, Diana Jimena Cano Schleich, Florence Wechsler, Michael E. Amaral, Rita Bourdin, Arnaud Brusselle, Guy G. Chen, Wenjia Chung, Li Ping Denton, Eve Fonseca, Joao A. Hoyte, Flavia Jackson, David J. Katial, Rohit Kirenga, Bruce J. Koh, Mariko Siyue Ławkiedraj, Agnieszka Lehtimäki, Lauri Liew, Mei Fong Mahboub, Bassam Martin, Neil Menzies-Gow, Andrew N. Pang, Pee Hwee Papaioannou, Andriana I. Patel, Pujan H. Perez-De-Llano, Luis Peters, Matthew J. Ricciardi, Luisa Rodríguez-Cáceres, Bellanid Solarte, Ivan Tay, Tunn Ren Torres-Duque, Carlos A. Wang, Eileen Zappa, Martina Abisheganaden, John Assing, Karin Dahl Costello, Richard W. Gibson, Peter G. Heffler, Enrico Máspero, Jorge Nicola, Stefania Perng, Diahn-Warng Steve Puggioni, Francesca Salvi, Sundeep Sheu, Chau-Chyun Sirena, Concetta Taillé, Camille Tan, Tze Lee Bjermer, Leif Canonica, Giorgio Walter Iwanaga, Takashi Jiménez-Maldonado, Libardo Taube, Christian Brussino, Luisa Price, David B. Lee Kong Chian School of Medicine (LKCMedicine) Tan Tock Seng Hospital National Healthcare Group, Singapore Medicine, Health and Life Sciences Biologics Biomarkers 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. Published version The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was conducted by the Observational and Pragmatic Research Institute (OPRI) Pte Ltd and was partially funded by Optimum Patient Care Global (OPCG) and AstraZeneca Ltd. No funding was received by the OPRI for its contribution. The International Severe Asthma Registry (ISAR) is operated by OPCG and co-funded by OPCG and AstraZeneca. 2024-09-03T05:43:52Z 2024-09-03T05:43:52Z 2024 Journal Article Porsbjerg, C. M., Townend, J., Bergeron, C., Christoff, G. C., Katsoulotos, G. P., Larenas-Linnemann, D., Tran, T. N., Al-Lehebi, R., Bosnic-Anticevich, S. Z., Busby, J., Hew, M., Kostikas, K., Papadopoulos, N. G., Pfeffer, P. E., Popov, T. A., Rhee, C. K., Sadatsafavi, M., Tsai, M., Ulrik, C. S., ...Price, D. B. (2024). Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma. Frontiers in Immunology, 15, 1361891-. https://dx.doi.org/10.3389/fimmu.2024.1361891 1664-3224 https://hdl.handle.net/10356/179929 10.3389/fimmu.2024.1361891 38711495 2-s2.0-85192184245 15 1361891 en Frontiers in Immunology © 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, Rodrıguez-Ca ́ ceres, ́ Solarte, Tay, Torres-Duque, Wang, Zappa, Abisheganaden, Assing, Costello, Gibson, Heffler, Maspero, Nicola, Perng (Steve), Puggioni, Salvi, Sheu, Sirena, ́ Taillé , Tan, Bjermer, Canonica, Iwanaga, Jimenez-Maldonado, Taube, Brussino ́ and Price. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. application/pdf |
| spellingShingle | Medicine, Health and Life Sciences Biologics Biomarkers Porsbjerg, Celeste M. Townend, John Bergeron, Celine Christoff, George C. Katsoulotos, Gregory P. Larenas-Linnemann, Désirée Tran, Trung N. Al-Lehebi, Riyad Bosnic-Anticevich, Sinthia Z. Busby, John Hew, Mark Kostikas, Konstantinos Papadopoulos, Nikolaos G. Pfeffer, Paul E. Popov, Todor A. Rhee, Chin Kook Sadatsafavi, Mohsen Tsai, Ming-Ju Ulrik, Charlotte Suppli Al-Ahmad, Mona Altraja, Alan Beastall, Aaron Bulathsinhala, Lakmini Carter, Victoria Cosio, Borja G. Fletton, Kirsty Hansen, Susanne Heaney, Liam G. Hubbard, Richard B. Kuna, Piotr Murray, Ruth B. Nagano, Tatsuya Pini, Laura Rosales, Diana Jimena Cano Schleich, Florence Wechsler, Michael E. Amaral, Rita Bourdin, Arnaud Brusselle, Guy G. Chen, Wenjia Chung, Li Ping Denton, Eve Fonseca, Joao A. Hoyte, Flavia Jackson, David J. Katial, Rohit Kirenga, Bruce J. Koh, Mariko Siyue Ławkiedraj, Agnieszka Lehtimäki, Lauri Liew, Mei Fong Mahboub, Bassam Martin, Neil Menzies-Gow, Andrew N. Pang, Pee Hwee Papaioannou, Andriana I. Patel, Pujan H. Perez-De-Llano, Luis Peters, Matthew J. Ricciardi, Luisa Rodríguez-Cáceres, Bellanid Solarte, Ivan Tay, Tunn Ren Torres-Duque, Carlos A. Wang, Eileen Zappa, Martina Abisheganaden, John Assing, Karin Dahl Costello, Richard W. Gibson, Peter G. Heffler, Enrico Máspero, Jorge Nicola, Stefania Perng, Diahn-Warng Steve Puggioni, Francesca Salvi, Sundeep Sheu, Chau-Chyun Sirena, Concetta Taillé, Camille Tan, Tze Lee Bjermer, Leif Canonica, Giorgio Walter Iwanaga, Takashi Jiménez-Maldonado, Libardo Taube, Christian Brussino, Luisa Price, David B. Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma |
| title | Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma |
| title_full | Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma |
| title_fullStr | Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma |
| title_full_unstemmed | Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma |
| title_short | Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma |
| title_sort | association between pre biologic t2 biomarker combinations and response to biologics in patients with severe asthma |
| topic | Medicine, Health and Life Sciences Biologics Biomarkers |
| url | https://hdl.handle.net/10356/179929 |
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