BACKGROUND: We examined levels of hyaluronan, a matrix glycosaminoglycan and 
versican, a matrix proteoglycan, in the sputum of asthmatics treated with 
mepolizumab (anti-IL-5 monoclonal antibody) versus placebo to evaluate the 
utility of these measurements as possible biomarkers of asthma control and 
airway remodeling.
METHODS: Patients with severe, prednisone-dependent asthma received either 
mepolizumab or placebo as described in a previously published randomized, 
double-blind, placebo-controlled study. We measured hyaluronan and versican 
levels by enzyme-linked immunosorbent assay in sputum collected before and after 
the 16-week treatment phase. Patients underwent a predefined prednisone tapering 
schedule if they remained exacerbation free, and sputum eosinophil percentage, 
asthma control questionnaire (ACQ) and spirometry were monitored.
RESULTS: After 6 months of mepolizumab therapy and prednisone tapering, there 
was a significant increase in sputum hyaluronan in the placebo group compared 
with baseline (p = 0.003). In contrast, there was a significant decrease in 
sputum hyaluronan in the active treatment group compared with placebo (p = 
0.007), which correlated with improvements in percent forced expiratory volume 
in 1 s (FEV1%) (p = 0.001) and ACQ scores (p = 0.009) as well as a decrease in 
sputum eosinophils (p = 0.02). There was a nonsignificant increase in sputum 
versican in the placebo group (p = 0.16), a decrease in the mepolizumab group (p 
= 0.13) and a significant inverse correlation between versican reduction and 
FEV1% improvement (p = 0.03).
CONCLUSIONS: Sputum hyaluronan values are reduced with mepolizumab therapy and 
correlate with improved clinical and spirometry values, suggesting this 
measurement may serve as a noninvasive biomarker of asthma control.