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

Am J Respir Crit Care Med. 2011 Apr 15;183(8):1007-14. doi: 10.1164/rccm.201008-1210OC. Epub 2010 Nov 5.


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) × 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.

Trial registration: ClinicalTrials.gov NCT00410280 NCT00725582.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Allergens / immunology
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / therapeutic use*
  • Asthma / drug therapy*
  • Double-Blind Method
  • Female
  • Forced Expiratory Volume
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Immunoglobulin G / therapeutic use
  • Interleukin-13 / antagonists & inhibitors*
  • Interleukin-13 / blood
  • Interleukin-13 / immunology
  • Male
  • Middle Aged
  • Sputum / cytology
  • Sputum / immunology
  • Treatment Outcome
  • Young Adult


  • Allergens
  • Antibodies, Neutralizing
  • Immunoglobulin G
  • Interleukin-13

Associated data

  • ClinicalTrials.gov/NCT00410280
  • ClinicalTrials.gov/NCT00725582