• Respiratory medicine · Feb 2016

    Randomized Controlled Trial Multicenter Study

    Reductions in eosinophil biomarkers by benralizumab in patients with asthma.

    • Tuyet-Hang Pham, Gautam Damera, Paul Newbold, and Koustubh Ranade.
    • Translational Sciences, MedImmune LLC, Gaithersburg, MD, USA. Electronic address: PhamTu@MedImmune.com.
    • Respir Med. 2016 Feb 1; 111: 21-9.

    BackgroundEosinophilic inflammation is frequently associated with increased asthma severity. Benralizumab is a humanized, afucosylated, anti-interleukin-5Rα monoclonal antibody that selectively depletes eosinophils and basophils through enhanced antibody-dependent cell-mediated cytotoxicity.ObjectiveTo study effects of benralizumab on eosinophil counts and activity following administration to asthma patients.MethodsSera were collected from asthma patients enrolled in two clinical studies. Placebo or benralizumab was subcutaneously administered to patients in Phase I (100 or 200 mg, multiple doses; N = 14; NCT00659659) and Phase IIa (25, 100, or 200 mg every 4 weeks; N = 24; NCT00783289) studies. Sera were also collected from healthy volunteers (N = 20) for comparison. Blood eosinophils, IL-5, eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), eotaxin/chemokine (C-C motif) 11 (CCL11), eotaxin-2/CCL24, tumor necrosis factor (TNF), and interferon-γ (IFN-γ) were measured at baseline and post-treatment.ResultsIncreased EDN concentrations were observed in sera of patients from both studies relative to healthy volunteers (p < 0.05). At baseline, sera EDN concentrations correlated with blood eosinophil counts (rs = 0.5; p < 0.05). Benralizumab reduced blood eosinophil numbers and sera EDN and ECP relative to baseline (p < 0.05). No changes in TNF or IFN-γ were observed, while serum IL-5, eotaxin/CCL11, and eotaxin-2/CCL24 increased after benralizumab administration vs. placebo (p < 0.05).ConclusionsIn two independent studies, serum IL-5, EDN, and ECP were modulated following benralizumab. Eosinophil depletion after benralizumab also resulted in significant reductions in EDN and ECP concentrations, suggesting that cytotoxic granule proteins were not released after eosinophil reduction.Copyright © 2016 Elsevier Ltd. All rights reserved.

      Pubmed     Free full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…