Dupilumab Suppresses Fractional Exhaled Nitric Oxide (FeNO) and Biomarkers of Type 2 Inflammation in Adult Patients with Persistent Uncontrolled Asthma Despite Use of Medium-to-High Dose Inhaled Corticosteroids Plus Long-Acting Beta-Agonists (ICS/LABAs)
Sunday, March 6, 2016: 4:45 PM
Concourse Foyer (Convention Center)
Brian N. Swanson, PhD, Ariel Teper, MD, Jennifer D. Hamilton, PhD, Bingzhi Zhang, PhD, Heribert Staudinger, MD, Nian Tian, Ying Wang, PhD, Jeffrey E. Ming, MD, PhD, Neil M.H. Graham, MD, Gianluca Pirozzi, MD, PhD
Rationale: Dupilumab, a fully human IL-4Rα monoclonal antibody, inhibits interleukins 4 and 13 signaling and showed significant efficacy in a phase 2b asthma trial (NCT01854047). We now report the effects of 24 weeks of dupilumab treatment on FeNO and blood biomarkers.

Methods: Adults (N=776) with persistent uncontrolled asthma for ≥12 months (medians: FEV1 = 62% of predicted; ACQ5 = 2.6) were randomized to 24 weeks of dupilumab (200 mg or 300 mg every 2 weeks [q2w] or every 4 weeks [q4w]), or placebo subcutaneously, on top of medium-to-high dose ICS/LABA. FeNO and blood biomarkers were measured using commercial assays. Percent changes from baseline were assessed using least-squares (LS) means derived from a mixed-effect model with repeated measures.

Results: LS mean percent changes from baseline to Week 24 for 300 mg q2w/200 mg q2w/placebo, respectively, were: FeNO (−29.4%/−21.9%/+10.9%), serum TARC (−26.7%/−29.4%/+11.0%), plasma eotaxin-3 (−26.6%/−37.8%/+20.0%), and serum total IgE (−46.9%/−52.2%/+11.6%); all P≤0.0001 versus placebo. Dupilumab suppressed FeNO, TARC and eotaxin-3 with near-maximal decreases by Week 2 which were similar and sustained for the q2w regimens, but smaller for q4w dosing. Serum total IgE gradually declined throughout dupilumab treatment without clear dose-differentiation, while total IgG, IgM and IgA did not decline compared to placebo. The most common adverse event was injection-site reaction (13–26% vs 13% placebo).

Conclusions: The 300 mg q2w and 200 mg q2w regimens of dupilumab achieved sustained suppression of type 2 inflammatory biomarkers versus placebo. A specific decline in IgE indicated immunoglobulin switching away from an allergic phenotype in dupilumab treated patients.