Porsbjerg, Celeste MTownend, JohnBergeron, CelineChristoff, George CKatsoulotos, Gregory PLarenas-Linnemann, DésiréeTran, Trung NAl-Lehebi, RiyadBosnic-Anticevich, Sinthia ZBusby, JohnHew, MarkKostikas, KonstantinosPapadopoulos, Nikolaos GPfeffer, Paul EPopov, Todor ARhee, Chin KookSadatsafavi, MohsenTsai, Ming-JuUlrik, Charlotte SuppliAl-Ahmad, MonaAltraja, AlanBeastall, AaronBulathsinhala, LakminiCarter, VictoriaGarcía-Cosío, BorjaFletton, KirstyHansen, SusanneHeaney, Liam GHubbard, Richard BKuna, PiotrMurray, Ruth BNagano, TatsuyaPini, LauraCano Rosales, Diana JimenaSchleich, FlorenceWechsler, Michael EAmaral, RitaBourdin, ArnaudBrusselle, Guy G.Chen, WenjiaChung, Li PingDenton, EveFonseca, Joao AHoyte, FlaviaJackson, David JKatial, RohitKirenga, Bruce JKoh, Mariko SiyueŁawkiedraj, AgnieszkaLehtimäki, LauriLiew, Mei FongMahboub, BassamMartin, NeilMenzies-Gow, Andrew NPang, Pee HweePapaioannou, Andriana IPatel, Pujan HPerez-De-Llano, LuisPeters, Matthew JRicciardi, LuisaRodríguez-Cáceres, BellanidSolarte, IvanTay, Tunn RenTorres-Duque, Carlos AWang, EileenZappa, MartinaAbisheganaden, JohnAssing, Karin DahlCostello, Richard W.Gibson, Peter GHeffler, EnricoMáspero, JorgeNicola, StefaniaPerng Steve, Diahn-WarngPuggioni, FrancescaSalvi, SundeepSheu, Chau-ChyunSirena, ConcettaTaillé, CamilleTan, Tze LeeBjermer, LeifCanonica, Giorgio WalterIwanaga, TakashiJiménez-Maldonado, LibardoTaube, ChristianBrussino, LuisaPrice, David B2024-05-102024-05-102024Porsbjerg CM, Townend J, Bergeron C, Christoff GC, Katsoulotos GP, Larenas-Linnemann D, et al. Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma. Front Immunol. 2024 Apr 19;15.https://hdl.handle.net/20.500.13003/20337To 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. 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. 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. 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. 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.engAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/AsthmaEosinophilsBiological ProductsAgedAdultLeukocyte CountHumansNitric OxideMiddle AgedMaleSeverity of Illness IndexBiomarkersFemaleAnti-Asthmatic AgentsImmunoglobulin ETreatment OutcomeCohort StudiesRegistriesresearch articleEstudios de CohortesResultado del TratamientoBiomarcadoresAntiasmáticosFemeninoInmunoglobulina EMasculinoHumanosPersona de Mediana EdadÓxido NítricoAsmaÍndice de Severidad de la EnfermedadAncianoEosinófilosProductos BiológicosAdultoRecuento de LeucocitosSistema de RegistrosAsthmaBiomarkersImmunoglobulin EEosinophilsBiological ProductsHumansMaleFemaleMiddle AgedAdultAnti-Asthmatic AgentsTreatment OutcomeRegistriesSeverity of Illness IndexLeukocyte CountNitric OxideAgedCohort Studies10.3389/fimmu.2024.13618911664-322438711495L20297176402-s2.0-85192184245001253451200001open access