INEXAS: A Phase 2 Randomized Trial of On-demand Inhaled Interferon Beta-1a in Severe Asthmatics.

Autor: McCrae C; Translational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA.; Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden., Olsson M; Early Biometrics and Statistical Innovation, Data Science and AI, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Gustafson P; BioPharmaceutical Medical, AstraZeneca, Gothenburg, Sweden., Malmgren A; Early Respiratory & Immunology Projects Department, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Aurell M; Early Respiratory & Immunology Clinical Development, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Fagerås M; BioPharmaceutical Medical, AstraZeneca, Gothenburg, Sweden., Da Silva CA; Early Respiratory & Immunology Clinical Development, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Cavallin A; Translational Science and Experimental Medicine, Early Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Paraskos J; Point of Care Diagnostics, Precision Medicine, Oncology R&D, AstraZeneca, Cambridge, UK., Karlsson K; Translational Science and Experimental Medicine, Early Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Wingren C; Translational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA., Monk P; Synairgen Research Ltd, Southampton University Hospital, Southampton, UK., Marsden R; Synairgen Research Ltd, Southampton University Hospital, Southampton, UK., Harrison T; Nottingham NIHR Biomedical Research Centre, University of Nottingham, Nottingham City Hospital, Nottingham, UK.
Jazyk: angličtina
Zdroj: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology [Clin Exp Allergy] 2021 Feb; Vol. 51 (2), pp. 273-283. Date of Electronic Publication: 2020 Nov 03.
DOI: 10.1111/cea.13765
Abstrakt: Background: Upper respiratory tract infections (URTIs) are important triggers for asthma exacerbations. We hypothesized that inhalation of the anti-viral cytokine, interferon (IFN)-β, during URTI, could prevent these exacerbations.
Objective: To evaluate the efficacy of on-demand inhaled IFN-β1a (AZD9412) to prevent severe asthma exacerbations following symptomatic URTI.
Methods: This was a randomized, double-blind, placebo-controlled trial in which patients with severe asthma (GINA 4-5; n = 121) reporting URTI symptoms were randomized to 14 days of once-daily nebulized AZD9412 or placebo. The primary endpoint was severe exacerbations during treatment. Secondary endpoints included 6-item asthma control questionnaire (ACQ-6) and lung function. Exploratory biomarkers included IFN-response markers in serum and sputum, blood leucocyte counts and serum inflammatory cytokines.
Results: Following a pre-planned interim analysis, the trial was terminated early due to an unexpectedly low exacerbation rate. Asthma worsenings were generally mild and tended to peak at randomization, possibly contributing to the lack of benefit of AZD9412 on other asthma endpoints. Numerically, AZD9412 did not reduce severe exacerbation rate, ACQ-6, asthma symptom scores or reliever medication use. AZD9412 improved lung function (morning peak expiratory flow; mPEF) by 19.7 L/min. Exploratory post hoc analyses indicated a greater mPEF improvement by AZD9412 in patients with high blood eosinophils (>0.3 × 10 9 /L) at screening and low serum interleukin-18 relative change at pre-treatment baseline. Pharmacodynamic effect of AZD9412 was confirmed using IFN-response markers.
Conclusions & Clinical Relevance: Colds did not have the impact on asthma patients that was expected and, due to the low exacerbation rate, the trial was stopped early. On-demand AZD9412 treatment did not numerically reduce the number of exacerbations, but did attenuate URTI-induced worsening of mPEF. Severe asthma patients with high blood eosinophils or low serum interleukin-18 response are potential subgroups for further investigation of inhaled IFN-β1a.
(@2020 AstraZeneca. International Journal of Cosmetic Science published by John Wiley & Sons.)
Databáze: MEDLINE
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