The effects of an anti–IL-13 mAb on cytokine levels and nasal symptoms following nasal allergen challenge Grant C. Nicholson, BSc, Harsha H. Kariyawasam,

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Presentation transcript:

The effects of an anti–IL-13 mAb on cytokine levels and nasal symptoms following nasal allergen challenge Grant C. Nicholson, BSc, Harsha H. Kariyawasam, MBBS, PhD, Andrew J. Tan, MSc, Jens M. Hohlfeld, MD, Deborah Quinn, MD, Christoph Walker, PhD, David Rodman, MD, John Westwick, PhD, Stipo Jurcevic, PhD, Onn Min Kon, MD, Peter J. Barnes, FMedSci, FRS, Norbert Krug, MD, Trevor T. Hansel, MBBCh, PhD Journal of Allergy and Clinical Immunology Volume 128, Issue 4, Pages 800-807.e9 (October 2011) DOI: 10.1016/j.jaci.2011.05.013 Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Overview of study design for the parallel group study that examined the effects of an mAbagainst IL-13 compared with placebo and topical nasal fluticasone propionate. Intravenous anti–IL-13 or intravenous placebo was administered on day 1, while NAC were performed at screening and on days 5, 6, and 7. Journal of Allergy and Clinical Immunology 2011 128, 800-807.e9DOI: (10.1016/j.jaci.2011.05.013) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 IL-13 levels in SAM eluates from individual subjects in relation to NAC. Anti–IL-13 treatment significantly decreased IL-13 levels when compared with placebo after NAC, expressed as AUC change from baseline (P < .05 on day 5 and P < .01 on day 7). Nasal fluticasone caused decreased IL-13 levels on day 5 (P < .05). Journal of Allergy and Clinical Immunology 2011 128, 800-807.e9DOI: (10.1016/j.jaci.2011.05.013) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 IL-5 levels in SAM eluates from individual subjects in relation to NAC. Data for each subject are connected, and each subject has an individual color code that is retained for Figs 2 and 3 in the publication. Nasal fluticasone significantly decreased IL-5 levels expressed as AUC change from baseline after NAC when compared with placebo (P < .01 on day 5). Journal of Allergy and Clinical Immunology 2011 128, 800-807.e9DOI: (10.1016/j.jaci.2011.05.013) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 TNSS in relation to NAC recorded from 0 to 8 hours on 4 separate visits (pretreatment/placebo, days 5, 6, and 7). Data are presented as medians at various times. There were no significant effects of anti–IL-13 treatment or fluticasone propionate treatment on TNSS in unselected patients. Journal of Allergy and Clinical Immunology 2011 128, 800-807.e9DOI: (10.1016/j.jaci.2011.05.013) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Levels of IL-13, IL-5, and eotaxin measured in SAM eluates are shown as box-whisker plots (median, quartiles, and range). Changes in nasal IL-13 AUC levels were found to be significantly decreased on day 5 (P < .05) and day 7 (P < .01) after anti–IL-13 treatment in comparison with placebo (Table II). Changes in IL-13 AUC levels on day 5 (P < .05) and IL-5 levels on day 5 (P < .01) were found to be significantly decreased after fluticasone propionate treatment versus placebo (Table II). AUC, Area under the curve. Journal of Allergy and Clinical Immunology 2011 128, 800-807.e9DOI: (10.1016/j.jaci.2011.05.013) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Eotaxin levels in SAM eluates from individual subjects in relation to NAC. Data for each subject are connected, and each subject has an individual color code that is also retained for Figs 2 and 3 in the published manuscript and in Fig E4. Journal of Allergy and Clinical Immunology 2011 128, 800-807.e9DOI: (10.1016/j.jaci.2011.05.013) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 The percentage of eosinophils among leukocytes in nasal lavage is presented. The eosinophil differential was obtained on light microscopy of stained cytospins from nasal lavages. Data are shown as box-whisker plots (median, quartiles, and range). Journal of Allergy and Clinical Immunology 2011 128, 800-807.e9DOI: (10.1016/j.jaci.2011.05.013) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 TNSS from the cohort receiving anti–IL-13 treatment. Subjects have been separated into high IL-13 (n = 4) and low IL-13 (n = 11) groups based on IL-13 levels measurement from SAM eluates at 7 and 8 hours post-NAC at screening. Post hoc analysis of TNSS between groups (high vs low IL-13 levels at screening) showed a trend for a difference on day 5 (P < .10) (Table E1). Journal of Allergy and Clinical Immunology 2011 128, 800-807.e9DOI: (10.1016/j.jaci.2011.05.013) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E5 TNSS from cohort receiving anti–IL-13 treatment. Subjects are separated into high IL-13 and low IL-13 groups based on IL-13 levels measurement from SAM eluates at 7 and 8 hours post-NAC at screening. Data are expressed as medians with quartiles and range. Post hoc analysis of TNSS between groups (high vs low IL-13 levels at screening) showed a trend for a difference on day 5 (P < .10) (Table E1). Journal of Allergy and Clinical Immunology 2011 128, 800-807.e9DOI: (10.1016/j.jaci.2011.05.013) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions