Lebrikizumab reduces serum periostin in asthma patients with elevated baseline periostin
Heleen Scheerens, Joseph R. Arron, David F. Choy, Sofia Mosesova, Preeti G. Lal, John G. Matthews
Abstract
Heleen Scheerens, Joseph R. Arron, David F. Choy, Sofia Mosesova, Preeti G. Lal, John G. Matthews
Abstract
Background: Periostin is a matricellular protein induced in airway epithelia by interleukin-13 (IL13) and a good systemic biomarker for IL13 activity. Lebrikizumab, a humanized monoclonal antibody, binds IL13 and improved lung function in moderate-to-severe asthma patients (pts) with elevated baseline serum periostin in a Phase II study. Aims: To examine the effect of blocking IL13 on systemic periostin levels in pts with uncontrolled asthma, despite inhaled corticosteriods. Methods: Pts (n=218) were randomized to lebrikizumab 250 mg (n=106) or placebo (PB) (n=112) SC every 4 weeks for 6 doses, with 12 weeks follow-up (NCT00930163). Serum periostin was measured at baseline and throughout the study. Pts were classified as periostin-high (≥median) or periostin-low ( Results: PB-corrected reductions in periostin were evident after 1 week of lebrikizumab treatment: 5.4% baseline reduction across all pts and 7.3% baseline reduction in periostin-high pts (p 90%) who were periostin-low at baseline maintained the periostin levels Conclusions: Lebrikizumab reduced serum periostin in periostin-high, but not periostin-low pts, vs placebo. These data suggest that in asthma pts, elevated serum periostin levels are dependent on IL13 activity.
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Background: Periostin is a matricellular protein induced in airway epithelia by interleukin-13 (IL13) and a good systemic biomarker for IL13 activity. Lebrikizumab, a humanized monoclonal antibody, binds IL13 and improved lung function in moderate-to-severe asthma patients (pts) with elevated baseline serum periostin in a Phase II study. Aims: To examine the effect of blocking IL13 on systemic periostin levels in pts with uncontrolled asthma, despite inhaled corticosteriods. Methods: Pts (n=218) were randomized to lebrikizumab 250 mg (n=106) or placebo (PB) (n=112) SC every 4 weeks for 6 doses, with 12 weeks follow-up (NCT00930163). Serum periostin was measured at baseline and throughout the study. Pts were classified as periostin-high (≥median) or periostin-low ( Results: PB-corrected reductions in periostin were evident after 1 week of lebrikizumab treatment: 5.4% baseline reduction across all pts and 7.3% baseline reduction in periostin-high pts (p 90%) who were periostin-low at baseline maintained the periostin levels Conclusions: Lebrikizumab reduced serum periostin in periostin-high, but not periostin-low pts, vs placebo. These data suggest that in asthma pts, elevated serum periostin levels are dependent on IL13 activity.
Key concepts: Periostin, Matricellular protein, Medicine, Asthma, Placebo, Biomarker, Internal medicine, Gastroenterology