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

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

Author information

1
Genentech, South San Francisco, CA, USA.

Abstract

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

PMID:
24131304
PMCID:
PMC4204278
DOI:
10.1111/cea.12220
[Indexed for MEDLINE]
Free PMC Article

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