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


OBJECTIVE
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.


RESULTS
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.


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.
McMaster University, 1200 Main St West, Hamilton, Ontario, Canada. gauvreau@mcmaster.ca
Gail M
GM
Gauvreau
Louis-Philippe
LP
Boulet
Donald W
DW
Cockcroft
J Mark
JM
Fitzgerald
Chris
C
Carlsten
Beth E
BE
Davis
Francine
F
Deschesnes
MyLinh
M
Duong
Billie L
BL
Durn
Karen J
KJ
Howie
Linda
L
Hui
Marion T
MT
Kasaian
Kieran J
KJ
Killian
Tara X
TX
Strinich
Richard M
RM
Watson
Nathalie
N
Y
Simon
S
Zhou
Donald
D
Raible
Paul M
PM
O'Byrne
D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology / Q000627:therapeutic use; D018793:Interleukin-13 / Q000037:antagonists & inhibitors* / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013183:Sputum / Q000166:cytology / Q000276:immunology; D016896:Treatment Outcome; D055815:Young Adult
D000485:Allergens; D057134:Antibodies, Neutralizing; D007074:Immunoglobulin G; D018793:Interleukin-13