Frontiers in Immunology (Apr 2024)

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

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

DOI
https://doi.org/10.3389/fimmu.2024.1361891
Journal volume & issue
Vol. 15

Abstract

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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 <0.001, respectively); however, this prediction was not improved by the addition of IgE.ConclusionsThe 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.

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