Dupilumab shows rapid and sustained suppression of inflammatory biomarkers in asthma patients in LIBERTY ASTHMA QUEST

Background: Dupilumab (DPL), a fully human anti-IL-4Rα mAb that inhibits IL-4/IL-13, is approved for treatment of adults with inadequately controlled moderate-to-severe atopic dermatitis. DPL previously suppressed type 2 inflammatory biomarkers during 24 weeks of treatment (NCT01854047). In a phase 3 study (NCT02414854), asthma patients (pts) aged ≥12 years, with no minimum baseline (BL) eosinophil requirement, uncontrolled with medium-to-high-dose ICS, plus 1 or 2 controllers received DPL 200/300mg or placebo (PBO) every 2 weeks for 52 weeks. DPL reduced severe asthma exacerbations, improved FEV1 and quality of life measures, and was generally well tolerated. Aim: Report effect of DPL on pharmacodynamic (PD) parameters. Methods: PD parameters: change from BL in FeNO, eotaxin-3, total IgE, periostin and TARC at Weeks 12 and 52. Results: BL biomarker values were elevated and comparable in all groups (Table). Pts receiving DPL demonstrated a statistically significant decrease in biomarkers concomitant with efficacy. A near-maximal effect was observed by Week 12 and sustained over the 52-week treatment period. Most common AE, with higher frequency in 200/300mg DPL vs PBO, was injection-site reactions (21%/24% vs 6%/14%). Conclusion: DPL showed rapid and sustained suppression of systemic and airway type 2 inflammatory biomarkers (including FeNO and IgE) in asthma pts, and was generally well tolerated.