- Title
- Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma
- Creator
- Porsbjerg, Celeste M.; Townend, John; Hew, Mark; Kostikas, Konstantinos; Papadopoulos, Nikolaos G.; Pfeffer, Paul E.; Popov, Todor A.; Rhee, Chin Kook; Sadatsafavi, Mohsen; Tsai, Ming-Ju; Ulrik, Charlotte Suppli; Al-Ahmad, Mona; Bergeron, Celine; Altraja, A; Beastall, A; Bulathsinhala, L; Carter, V; Cosio, BG; Fletton, K; Hansen, S; Heaney, LG; Hubbard, RB; Kuna, P; Christoff, George C.; Murray, RB; Nagano, T; Pini, L; Cano Rosales, DJ; Schleich, F; Wechsler, ME; Amaral, R; Bourdin, A; Brusselle, GG; Chen, W; Katsoulotos, Gregory P.; Chung, LP; Denton, E; Fonseca, JA; Hoyte, F; Jackson, DJ; Katial, R; Kirenga, BJ; Koh, MS; Ławkiedraj, A; Lehtimäki, L; Larenas-Linnemann, Desiree; Liew, MF; Mahboub, B; Martin, N; Menzies-Gow, AN; Pang, PH; Papaioannou, AI; Patel, PH; Perez-De-Llano, L; Peters, MJ; Ricciardi, L; Tran, Tran N.; Rodríguez-Cáceres, B; Solarte, I; Tay, TR; Torres-Duque, CA; Wang, E; Zappa, M; Abisheganaden, J; Assing, KD; Costello, RW; Gibson, Peter G.; Al-Lehebi, Riyad; Heffler, E; Máspero, J; Nicola, S; Perng, DW; Puggioni, F; Salvi, S; Sheu, CC; Sirena, C; Taillé, C; Tan, TL; Bosnic-Anticevich, Sinthia Z.; Bjermer, L; Canonica, GW; Iwanaga, T; Jiménez-Maldonado, L; Taube, C; Brussino, L; Price, DB; Busby, John
- Relation
- Frontiers in Immunology Vol. 15, no. 1361891
- Publisher Link
- http://dx.doi.org/10.3389/fimmu.2024.1361891
- Publisher
- Frontiers Research Foundation
- Resource Type
- journal article
- Date
- 2024
- Description
- 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.
- Subject
- severe asthma; biomarkers; eosinophil (EOS); FeNO (fraction of exhaled nitric oxide); biologics; FEV1; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1503688
- Identifier
- uon:55374
- Identifier
- ISSN:1664-3224
- Language
- eng
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