TY - JOUR T1 - Therapeutic blockade of IL-4 and 13 signaling with dupilumab (SAR231893/REGN668) inhibits key biomarkers in asthma JF - European Respiratory Journal JO - Eur Respir J VL - 42 IS - Suppl 57 SP - 3539 AU - Sally Wenzel AU - Jeffrey Ming AU - Jennifer Hamilton AU - Allen Radin AU - Ross Rocklin AU - Thomas Hultsch AU - Lin Wang AU - Franck Skobieranda AU - Gianluca Pirozzi Y1 - 2013/09/01 UR - http://erj.ersjournals.com/content/42/Suppl_57/3539.abstract N2 - Dupilumab is a potent inhibitor of interleukin (IL) 4 and 13 cytokines implicated in asthma.Moderate-to-severe, persistent asthma patients treated with medium-to-high dose inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA) and with blood eosinophils >300 cells/µL (101 patients) or sputum eosinophils >3% (3 patients) were administered dupilumab or placebo for 12 weeks or until asthma exacerbation. At Week 4, LABA was withdrawn. Fluticasone was then withdrawn over 3-4 weeks. Fractional exhaled nitric oxide (FeNO), serum thymus and activation regulated chemokine (TARC), immunoglobulin E (IgE), eotaxin-3 and blood eosinophils were measured. Mixed model analysis with least square mean values are reported.FeNO markedly decreased despite ICS withdrawal (dupilumab vs placebo mean % change at Week 12: -28.7% vs +35.0%; p<0.001). TARC (-22.7% vs +0.3%; p<0.001) and eotaxin-3 (-39.6% vs +12.7%; p<0.001) decreased within 1 week and persisted at Week 12 (TARC: -26.0% vs +7.6%; p<0.001; eotaxin-3: -45.7% vs +5.1%; p<0.001). IgE decreased at Week 4 (-10.1% vs +13.5%; p=0.03) and was further reduced at Week 12 (-36.8% vs -5.5%; p<0.001). No statistically significant change in blood eosinophils was observed at Week 12. Overall, the forced expiratory volume in 1 second (FEV1) improved on dupilumab and this correlated with reduction in FeNO (r=-0.408, p=0.009) at Week 12.Dupilumab reduced bronchial and systemic biomarkers associated with T-helper 2 inflammation (FeNO, TARC, eotaxin-3, IgE) in moderate-to-severe persistent asthma patients. The correlation between reduced FeNO and improved FEV1 suggests that effects on Th2 inflammation lead to improved pulmonary function. ER -