RT Journal Article
SR Electronic
T1 Lebrikizumab reduces serum periostin in asthma patients with elevated baseline periostin
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P2167
VO 40
IS Suppl 56
A1 Heleen Scheerens
A1 Joseph Arron
A1 David Choy
A1 Sofia Mosesova
A1 Preeti Lal
A1 John Matthews
YR 2012
UL http://erj.ersjournals.com/content/40/Suppl_56/P2167.abstract
AB 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 (<median) based on baseline serum levels.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<0.001). At 12 weeks, periostin reductions were 9.7% (p<0.001) for all lebrikizumab-treated pts vs PB and 14.4% (p<0.001) in periostin-high pts. Periostin-low pts had no significant reduction in periostin (2.9%; p=0.3). This effect was sustained at Week 32. Most pts (>90%) who were periostin-low at baseline maintained the periostin levels <median, whereas 72% of periostin-high pts treated with PB and only 40% treated with lebrikizumab maintained periostin levels ≥median at Week 12.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.