Effects of Interleukin-13 Blockade on Allergen-induced Airway Responses in Mild Atopic Asthma.
Rationale: Extensive evidence in animal models supports a role for IL-13 in the pathobiology of asthma. IMA-638 and IMA-026 are fully humanized IgG(1) antibodies that bind to different epitopes and neutralize IL-13 bioactivity. Objectives: We hypothesized that anti-IL-13 treatment would inhibit alle...
| Publicado en: | American Journal of Respiratory & Critical Care Medicine Vol. 183; no. 8; pp. 1007 - 1015 |
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| Autores principales: | , , , , , , , , , , , , , , , , , , |
| Formato: | research randomized controlled trial Journal Article |
| Publicado: |
Oxford University Press / USA
4/15/2011
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104873215&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104873215 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 1073449X 1FG jtl: American Journal of Respiratory & Critical Care Medicine issn: 1073449X maglogo: N pubinfo: dt: 4/15/2011 vid: 183 iid: 8 pid: 622 pub: Oxford University Press / USA artinfo: ui: 104873215 2011013816 10.1164/rccm.201008-1210OC NLM21057005 104873215 ppf: 1007 ppct: 8 formats: tig: atl: Effects of Interleukin-13 Blockade on Allergen-induced Airway Responses in Mild Atopic Asthma. aug: au: Gauvreau GM Boulet LP Cockcroft DW Fitzgerald JM Carlsten C Davis BE Deschesnes F Duong M Durn BL Howie KJ Hui L Kasaian MT Killian KJ Strinich TX Watson RM Y N Zhou S Raible D O'Byrne PM affil: HSC 3U26, McMaster University, 1200 Main St West, Hamilton, ON, L8N 3Z5 Canada. gauvreau@mcmaster.ca. sug: subj: Antibodies Therapeutic Use Asthma Drug Therapy Interleukins Antagonists and Inhibitors Adolescence Adult Allergens Immunology Antibodies Blood Antibodies Immunology Double-Blind Studies Female Forced Expiratory Volume Human Immunoglobulins Blood Immunoglobulins Immunology Immunoglobulins Therapeutic Use Interleukins Blood Interleukins Immunology Male Middle Age Randomized Controlled Trials Sputum Sputum Immunology Treatment Outcomes Young Adult Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Female Male ab: Rationale: Extensive evidence in animal models supports a role for IL-13 in the pathobiology of asthma. IMA-638 and IMA-026 are fully humanized IgG(1) antibodies that bind to different epitopes and neutralize IL-13 bioactivity. Objectives: We hypothesized that anti-IL-13 treatment would inhibit allergen-induced late-phase asthmatic responses, airway hyperresponsiveness, and inflammation in subjects with asthma. Methods: Fifty-six subjects with mild, atopic asthma were recruited for two double-blind, randomized, placebo-controlled, parallel group trials to compare IMA-638 and IMA-026 IL-13 antibody treatments with placebo treatment. Drug was administered on Days 1 and 8, and allergen challenges were performed on Days 14 and 35. The primary outcome variable was the late-phase area under the curve (AUC), and secondary outcome variables were the early- and late-phase maximum percent fall in FEV(1), early AUC, allergen-induced shift in airway hyperresponsiveness, and sputum eosinophils. Measurements and Main Results: The treatment difference with IMA-638 on Day 14 was -19.1 FEV(1) x hour (95% confidence interval: -36.2, -1.9) for the allergen-induced early AUC and -23.8 FEV(1) x hour (95% confidence interval: -46.4, -1.2) for the late AUC (both P < 0.05), but this effect was lost by Day 35. Treatment with IMA-026 did not attenuate the asthmatic responses on Day 14 or Day 35. There was no effect of either antibody on allergen-induced airway hyperresponsiveness or sputum eosinophils. The frequency of adverse events after administration of the IL-13 antibodies was similar to placebo. Conclusions: IL-13 has a role in allergen-induced airway responses in humans. Further study is required to determine whether anti-IL-13 monoclonal antibodies will be beneficial clinically. Clinical trial registered with www.clinicaltrials.gov (NCT 00410280 and NCT 00725582). pubtype: Academic Journal doctype: research randomized controlled trial Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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