Blood eosinophils predict therapeutic effects of a GATA3-specific DNAzyme in asthma patients Norbert Krug, MD, Jens M. Hohlfeld, MD, Roland Buhl, MD,

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Presentation transcript:

Blood eosinophils predict therapeutic effects of a GATA3-specific DNAzyme in asthma patients Norbert Krug, MD, Jens M. Hohlfeld, MD, Roland Buhl, MD, Jonas Renz, MA, Holger Garn, PhD, Harald Renz, MD Journal of Allergy and Clinical Immunology Volume 140, Issue 2, Pages 625-628.e5 (August 2017) DOI: 10.1016/j.jaci.2017.02.024 Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Patient flowchart and study protocol. Twenty-one patients in the SB010 treatment group and 19 patients in the placebo group reached the primary end point of the study. Patients were further stratified according to prespecified subgroups defined by relative blood eosinophil counts at enrollment. AC, Allergen challenge; Eos, eosinophil; MCh, methacholine provocation for airway hyperresponsiveness analysis; n.e., not eligible; SAE, severe adverse event. Journal of Allergy and Clinical Immunology 2017 140, 625-628.e5DOI: (10.1016/j.jaci.2017.02.024) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Lung function following allergen challenges before and after 4 weeks of treatment. Pretreatment and posttreatment FEV1 curves (as percent of baseline) for SB010 ■ and placebo ▲ treatment for subgroups with blood eosinophils of 3% or more, 4% or more, and 5% or more, respectively (mean values ± SEM). Insert boxes indicate % improvement in the area under the FEV1 curve (AUC) in the SB010 treatment group as compared with placebo for the early-phase response (left box, Wilcoxon rank sum test) and the late-phase response (right box, analysis of covariance). Journal of Allergy and Clinical Immunology 2017 140, 625-628.e5DOI: (10.1016/j.jaci.2017.02.024) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Overview of study design and procedures. AC, Allergen challenge; D, day; hgd40, human GATA-3 DNAzyme 40 for inhaled application; IS, induced sputum; MCh, methacholine provocation for airway hyperresponsiveness analysis. Journal of Allergy and Clinical Immunology 2017 140, 625-628.e5DOI: (10.1016/j.jaci.2017.02.024) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Changes in sputum eosinophils and blood IL-5 levels following allergen challenge before and after treatment with placebo or SB010. Relative sputum eosinophil numbers (left) and blood IL-5 concentrations (right) were measured after the pretreatment and posttreatment allergen challenges. Absolute changes were calculated and expressed as means ± SEM for all the 3 subgroups for each treatment condition, respectively. Positive values reflect increased levels after posttreatment challenges as compared with pretreatment values, and, vice versa, negative values reflect lower levels after treatment. For IL-5, all patients were evaluated who exhibited detectable blood IL-5 levels either before and/or after treatment. Journal of Allergy and Clinical Immunology 2017 140, 625-628.e5DOI: (10.1016/j.jaci.2017.02.024) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Relative changes in Feno levels at day 13 following allergen challenge and onset of treatment. Eos, Eosinophils. Feno levels were determined at pretreatment/prechallenge and at day 13 after allergen challenge and onset of placebo or SB010 treatment. Data are expressed as percent change compared with prechallenge values for the 3 subgroups identified by increasing prechallenge blood eosinophil counts. Noteworthy to mention that initial changes in Feno levels directly after allergen challenge were comparably high in all subgroups. Journal of Allergy and Clinical Immunology 2017 140, 625-628.e5DOI: (10.1016/j.jaci.2017.02.024) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 Changes in lung function following allergen challenges before and after 4 weeks of treatment in a subgroup of patients stratified by 40 ppb or more prechallenge Feno levels compared with the whole patient population. Shown are differences in percent changes in area under the curve (A) or maximum decline (B) in FEV1 following allergen challenges before and after 4 weeks of treatment between placebo and SB010 treatment groups of the whole patient population (black bars) or patients with 40 ppb or more Feno before initial allergen challenge for the late allergic response (LAR; left) and the early allergic response (EAR; right). Journal of Allergy and Clinical Immunology 2017 140, 625-628.e5DOI: (10.1016/j.jaci.2017.02.024) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions