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