Details

Autor(en) / Beteiligte

• Gauvreau, Gail M
• Boulet, Louis-Philippe
• Cockcroft, Donald W
• Fitzgerald, J Mark
• Carlsten, Chris
• Davis, Beth E
• Deschesnes, Francine
• Duong, MyLinh
• Durn, Billie L
• Howie, Karen J
• Hui, Linda
• Kasaian, Marion T
• Killian, Kieran J
• Strinich, Tara X
• Watson, Richard M
• Y, Nathalie
• Zhou, Simon
• Raible, Donald
• O'Byrne, Paul M

Titel

Effects of interleukin-13 blockade on allergen-induced airway responses in mild atopic asthma

Ist Teil von

• American journal of respiratory and critical care medicine, 2011-04, Vol.183 (8), p.1007-1014

Ort / Verlag

United States: American Thoracic Society

Erscheinungsjahr

2011

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. We hypothesized that anti-IL-13 treatment would inhibit allergen-induced late-phase asthmatic responses, airway hyperresponsiveness, and inflammation in subjects with asthma. 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. The treatment difference with IMA-638 on Day 14 was -19.1 FEV(1) × hour (95% confidence interval: -36.2, -1.9) for the allergen-induced early AUC and -23.8 FEV(1) × 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. 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.