Response to biologics along a gradient of T2 involvement in patients with severe asthma: a data-driven biomarker clustering approach
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Wang,Eileen;Henley,William;Larenas-Linnemann,Désirée;Bulathsinhala,Lakmini;Tran,Trung N.;Wechsler,Michael E.;Aaron,Shawn D.;Al-Ahmad,Mona;Al-Lehebi,Riyad;Altraja,Alan;Barker,Peter;Beastall,Aaron;Belevskiy,Andrey S.;Bergeron,Celine;Bjermer,Leif;Björnsdóttir,Unnur S.;Bosnic-Anticevich,Sinthia Z.;Bourdin,Arnaud;Brusselle,Guy G.;Busby,John;Canonica,Giorgio Walter;Carter,Victoria;Chapman,Kenneth R.;Chapman,Nicholas;Christoff,George C.;Cosio,Borja G.;Costello,Richard W.;Fingleton,James;Ioa Fonseca,João A.;Gaga,Mina;Gibson,Peter G.;Hansen,Susanne;Heaney,Liam G.;Heffler,Enrico;Hew,Mark;Horiguchi,Takahiko;Hoyte,Flavia;Hubbard,Richard B.;Iwanaga,Takashi;Jackson,David J.;Katial,Rohit;Koh,Mariko Siyue;Kostikas,Konstantinos;Kuna,Piotr;Lehmann,Sverre;Lehtimäki,Lauri;Louis,Renaud;LúdvÃksdóttir,Dóra;Lugogo,Njira;Mahboub,Bassam;Martin,Neil;Máspero,Jorge;Menzies-Gow,Andrew N.;Mohan,Arjun;Murray,Ruth B.;Nagano,Tatsuya;Papadopoulos,Nikolaos G.;Papaioannou,Andriana I.;Patel,Pujan H.;Perez-de-Llano,Luis;Perng,Diahn-Warng;Peters,Matthew J.;Pfeffer,Paul E.;Pitrez,Paulo Márcio;Pleasants,Roy Alton;Popov,Todor A.;Porsbjerg,Celeste M.;Puggioni,Francesca;Quinton,Anna;Rhee,Chin Kook;Sadatsafavi,Mohsen;Salvi,Sundeep;Scioscia,Giulia;Sheu,Chau-Chyun;Sirena,Concetta;Taillé,Camille;Taube,Christian;Torres-Duque,Carlos A.;Tsai,Ming-Ju;Tunsäter,Alf;Ulrik,Charlotte Suppli;Price,David B.
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2025
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BACKGROUND: Asthma with low levels of T2-biomarkers is poorly understood. OBJECTIVE: To characterize severe asthma phenotypes and compare pre- to post-biologic change in asthma outcomes along a gradient of T2-involvement. METHODS: This was a registry-based, cohort study including data from 24 countries. Biomarker distribution (BEC, FeNO, IgE) was quantified pre-biologic initiation. Clusters were identified using a five-component Gaussian finite mixture model and phenotypically characterized. Change in asthma and healthcare utilization outcomes between 1-year pre- and post-biologic initiation were compared between clusters and by biologic class. RESULTS: Amongst 3,675 patients Five biomarker clusters) were identified along a gradient of T2-involvement: Cluster A with the lowest T2-involvement (16.4%), Cluster B (20.4%), Cluster C (22.9%), Cluster D (30.3%), and cluster E with the highest T2-involvement (10.0%). In multivariable analysis, biologic use was associated with improved outcomes in all clusters but tended to be better at the higher end of the T2 spectrum. For example, patients in cluster C had a significantly greater increase in FEV(1) relative to cluster A (difference 0.16L [95% CI 0.08, 0.25]; p<0.001). The odds of uncontrolled asthma were approximately 0.6 for all clusters relative to cluster A.Overall, exacerbation rates were lower and greater improvements in lung function and asthma control were noted for anti-IL-5/5R (but not anti-IgE or anti-IL4Rα) for all clusters relative to cluster A. CONCLUSION: T2-targeting biologics have utility in the management of asthma with low T2 involvement, but more effective therapies are needed. Further research is warranted to identify specific pathogenic pathways at the lower end of the T2 spectrum that can be effectively targeted by biologics.
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The journal of allergy and clinical immunology.In practice