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Relationship Between Benralizumab Exposure and Efficacy for Patients With Severe Eosinophilic Asthma

We evaluated the relationship between benralizumab (30 mg every 4 and 8 weeks (Q4W, Q8W)) pharmacokinetic (PK) exposure and end points of asthma exacerbation rates (AERs) and change from baseline in prebronchodilator forced expiratory volume in 1 second (FEV (1)) for patients with severe, uncontroll...

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Detalles Bibliográficos
Autores principales: Chia, Yen Lin, Yan, Li, Yu, Binbing, Wang, Bing, Barker, Peter, Goldman, Mitchell, Roskos, Lorin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767326/
https://www.ncbi.nlm.nih.gov/pubmed/30661249
http://dx.doi.org/10.1002/cpt.1371
Descripción
Sumario:We evaluated the relationship between benralizumab (30 mg every 4 and 8 weeks (Q4W, Q8W)) pharmacokinetic (PK) exposure and end points of asthma exacerbation rates (AERs) and change from baseline in prebronchodilator forced expiratory volume in 1 second (FEV (1)) for patients with severe, uncontrolled eosinophilic asthma in the SIROCCO/CALIMA phase III trials. In empirical assessment, AER ratios in SIROCCO were similar across PK quartiles. However, the lowest PK quartile in CALIMA had reduced efficacy; low CALIMA placebo AER possibly confounded this result. In population modeling, estimated benralizumab 90% effective concentration for AER reduction was 927 ng/mL, below the Q8W dosage steady‐state average PK concentration (1,066 ng/mL). Benralizumab treatment resulted in more rapid FEV (1) improvement vs. placebo (estimated half‐maximum time: 7.6 vs. 18 days); this response was greater for patients with greater baseline eosinophil counts. These results confirmed 30 mg Q8W is the optimal benralizumab dosage for patients with severe eosinophilic asthma.