학술논문
Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma
Document Type
article
Author
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-Ahmad; Alan 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 (Steve); 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
Source
Frontiers in Immunology, Vol 15 (2024)
Subject
Language
English
ISSN
1664-3224
Abstract
BackgroundTo 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.AimTo elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life.MethodsThis 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.ResultsOverall, 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