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

Data de publicação: Data Ahead of Print:

Autores da FMUP

  • João De Almeida Lopes Da Fonseca

    Autor

Participantes de fora da FMUP

  • Porsbjerg CM
  • Townend J
  • Bergeron C
  • Christoff GC
  • Katsoulotos GP
  • Larenas-Linnemann D
  • Tran TN
  • Al-Lehebi R
  • Bosnic-Anticevich SZ
  • Busby J
  • Hew M
  • Kostikas K
  • Papadopoulos NG
  • Pfeffer PE
  • Popov TA
  • Rhee CK
  • Sadatsafavi M
  • Tsai MJ
  • Ulrik CS
  • Al-Ahmad M
  • Altraja A
  • Beastall A
  • Bulathsinhala L
  • Carter V
  • Cosio BG
  • Fletton K
  • Hansen S
  • Heaney LG
  • Hubbard RB
  • Kuna P
  • Murray RB
  • Nagano T
  • Pini L
  • Cano Rosales DJ
  • Schleich F
  • Wechsler ME
  • Amaral R
  • Bourdin A
  • Brusselle GG
  • Chen W
  • Chung LP
  • Denton E
  • Hoyte F
  • Jackson DJ
  • Katial R
  • Kirenga BJ
  • Koh MS
  • Lawkiedraj A
  • Lehtimäki L
  • Liew MF
  • Mahboub B
  • Martin N
  • Menzies-Gow AN
  • Pang PH
  • Papaioannou AI
  • Patel PH
  • Perez-De-Llano L
  • Peters MJ
  • Ricciardi L
  • Rodríguez-Cáceres B
  • Solarte I
  • Tay TR
  • Torres-Duque CA
  • Wang E
  • Zappa M
  • Abisheganaden J
  • Assing KD
  • Costello RW
  • Gibson PG
  • Heffler E
  • Máspero J
  • Nicola S
  • Perng Steve DW
  • Puggioni F
  • Salvi S
  • Sheu CC
  • Sirena C
  • Taillé C
  • Tan TL
  • Bjermer L
  • Canonica GW
  • Iwanaga T
  • Jiménez-Maldonado L
  • Taube C
  • Brussino L
  • Price DB

Unidades de investigação

Abstract

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 FEV(1) for both anti-IgE and anti-IL5/5R, with a trend for anti-IL4Ra. Mean FEV(1) 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-IL4Ra, 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-IL4Ra, 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 FEV(1) increase (adjusted R(2): 0.751), compared to BEC (adjusted R(2): 0.747) or FeNO alone (adjusted R(2): 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.

Copyright © 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, Lawkiedraj, Lehtimäki, Liew, Mahboub, Martin, Menzies-Gow, Pang, Papaioannou, Patel, Perez-De-Llano, Peters, Ricciardi, Rodríguez-Cáceres, Solarte, Tay, Torres-Duque, Wang, Zappa, Abisheganaden, Assing, Costello, Gibson, Heffler, Máspero, Nicola, Perng (Steve), Puggioni, Salvi, Sheu, Sirena, Taillé, Tan, Bjermer, Canonica, Iwanaga, Jiménez-Maldonado, Taube, Brussino and Price.

Dados da publicação

ISSN/ISSNe:
1664-3224, 1664-3224

Frontiers in Immunology  Frontiers Media S.A.

Tipo:
Article
Páginas:
1361891-1361891
Link para outro recurso:
www.scopus.com

Citações Recebidas na Web of Science: 1

Citações Recebidas na Scopus: 1

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Keywords

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

Proyectos asociados

Prevalence and Characterisation of Asthma Patients According to Disease Severity in Portugal (EPI-ASTHMA) - NCT05169619

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Estudo Clínico Observacional (EPI-ASTHMA) . AstraZeneca . 2021

Effect of a Mobile App on Improving Asthma Control in Adolescents and Adults With Persistent Asthma: A Pilot Randomized Multicentre, Superiority Clinical Trial (mINSPIRERS) - NCT05129527

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Ensaio Clínico Académico (mINSPIRERS) . 2021

Utilização em estudos observacionais do Registo de Asma Grave Portugal.

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Estudo Observacional Académico (RAG) . 2020

Clinical Research Collaboration Severe Heterogenous Asthma Research collaboration, Patient-centered (CRC SHARP).

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Estudo Clínico Observacional (SHARP) . European Respiratory Society . 2021

Multidimensional phenotyping of severe asthma patients and its impact on disease control and therapeutic response - analysis from the Portuguese Severe Asthma Registry.

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Estudo Clínico Observacional (RAG-SPP-GSK) . SPPneumologia . 2022

BREATHE - An oBservational, pRimary data study to characterize severe AsThma pHenotypes and assEss disease burden across the EUCAN region.

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Estudo Clínico Observacional (RAG-AZ-BREATHE) . AstraZeneca . 2022

Efficiency in Spine Care ? Assessing outcomes and costs to inform healthcare improvement

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Estudo Clínico Académico . 2022

Use of secondary data, health technology assessment methods and economic modelling applied to penicillin allergy

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Estudo Clínico Académico . 2020

Using different data sources for the identification of asthma patients and those at high risk of adverse outcomes

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Estudo Clínico Académico . 2020

Phenotypes of Chronic Diseases of the Airways: Towards Multidimensional Data -Driven Profiling

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