Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma

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

Research output: Journal PublicationArticlepeer-review


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.

Original languageEnglish
Article number1361891
JournalFrontiers in Immunology
Publication statusPublished - 2024
Externally publishedYes


  • biologics
  • biomarkers
  • eosinophil (EOS)
  • FeNO (Fraction of exhaled Nitric Oxide)
  • FEV1
  • personalized medicine (PM)
  • severe asthma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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