The effects of lebrikizumab in patients with mild asthma following whole lung allergen challenge

Clin Exp Allergy. 2014 Jan;44(1):38-46. doi: 10.1111/cea.12220.


Background: Interleukin 13 (IL13) is a T-helper type 2 (Th2) cytokine associated with inflammation and pathology in allergic diseases such as bronchial asthma. We have shown that treatment with lebrikizumab, an anti-IL13 monoclonal antibody, significantly improves prebronchodilator forced expiratory volume in 1 s (FEV(1)) in a subset of subjects with uncontrolled asthma.

Objective: To evaluate efficacy and safety of lebrikizumab in subjects with mild asthma who underwent bronchial allergen challenge.

Methods: Twenty-nine subjects were randomized 1 : 1-5 mg/kg lebrikizumab (n = 13) or placebo (n = 16) administered subcutaneously every 4 weeks over 12 weeks, a total of four doses. Primary efficacy outcome was late asthmatic response (LAR) at Week 13, defined as area under the curve of FEV1 measured 2-8 h following inhaled allergen challenge. Serum biomarkers were measured to verify IL13 pathway inhibition and identify patients with an increased response to lebrikizumab.

Results: At Week 13, the LAR in lebrikizumab subjects was reduced by 48% compared with placebo subjects, although this was not statistically significant (95% confidence interval, -19%, 90%). Exploratory analysis indicated that lebrikizumab-treated subjects with elevated baseline levels of peripheral blood eosinophils, serum IgE, or periostin exhibited a greater reduction in LAR compared with subjects with lower baseline levels of these biomarkers. Lebrikizumab exerted systemic effects on markers of Th2 inflammation, reducing serum immunoglobulin E (IgE), chemokine ligands 13 and 17 by approximately 25% (P < 0.01). Lebrikizumab was well tolerated.

Conclusion and clinical relevance: Lebrikizumab reduced the LAR in subjects with mild asthma. Clinical trial number NCT00781443.

Keywords: IL13; Th2 inflammation; allergen challenge; asthma; biomarkers; lebrikizumab.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Allergens / immunology*
  • Anti-Asthmatic Agents / adverse effects
  • Anti-Asthmatic Agents / pharmacology
  • Anti-Asthmatic Agents / therapeutic use*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Asthma / blood
  • Asthma / drug therapy*
  • Asthma / immunology*
  • Biomarkers / blood
  • Bronchial Provocation Tests
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Interleukin-13
  • Lung / immunology
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Treatment Outcome
  • Young Adult


  • Allergens
  • Anti-Asthmatic Agents
  • Antibodies, Monoclonal
  • Biomarkers
  • Interleukin-13
  • lebrikizumab

Associated data