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

Autores da FMUP
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
- Tipo:
- Article
- Páginas:
- 1361891-1361891
- Link para outro recurso:
- www.scopus.com
Frontiers in Immunology Frontiers Media S.A.
Citações Recebidas na Web of Science: 1
Citações Recebidas na Scopus: 1
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Filiações
Keywords
- FEV1; FeNO (Fraction of exhaled Nitric Oxide); biologics; biomarkers; eosinophil (EOS); personalized medicine (PM); severe asthma
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Citar a publicação
Porsbjerg CM,Townend J,Bergeron C,Christoff GC,Katsoulotos GP,Larenas D,Tran TN,Al R,Bosnic SZ,Busby J,Hew M,Kostikas K,Papadopoulos NG,Pfeffer PE,Popov TA,Rhee CK,Sadatsafavi M,Tsai MJ,Ulrik CS,Al 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 DJ,Schleich F,Wechsler ME,Amaral R,Bourdin A,Brusselle GG,Chen W,Chung LP,Denton E,Fonseca JA,Hoyte F,Jackson DJ,Katial R,Kirenga BJ,Koh MS,Lawkiedraj A,Lehtimäki L,Liew MF,Mahboub B,Martin N,Menzies AN,Pang PH,Papaioannou AI,Patel PH,Perez L,Peters MJ,Ricciardi L,Rodríguez B,Solarte I,Tay TR,Torres CA,Wang E,Zappa M,Abisheganaden J,Assing KD,Costello RW,Gibson PG,Heffler E,Máspero J,Nicola S,Perng DW,Puggioni F,Salvi S,Sheu CC,Sirena C,Taillé C,Tan TL,Bjermer L,Canonica GW,Iwanaga T,Jiménez L,Taube C,Brussino L,Price DB. Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma. Front. Immunol. 2024. 15. p. 1361891-1361891. IF:7,300. (1).