Introduction: In a pivotal phase 2b trial (NCT01854047), adult patients (pts) with uncontrolled persistent asthma using ICS+LABA were randomized to 24 weeks (wks) of add-on therapy with dupilumab (DPL; an anti-IL-4Rα antibody), 200 or 300 mg every 2 weeks (q2w) or q4w, or placebo (PBO). DPL significantly reduced the rate of severe exacerbation when administered q2w. Most common adverse events (DPL vs PBO) were upper respiratory tract infections (12−15% vs 18%) and injection site erythema (8−22% vs 8%). We aimed to evaluate whether DPL, a dual antagonist of both IL-4 and IL-13, reduced severe exacerbations irrespective of baseline levels of serum periostin (PN; a biomarker of IL-13 activity). Methods: PN was assayed by ELISA (Shino-Test, Tokyo). Annualized rates of severe exacerbation in the 24-wk treatment period are given for “PN-high” and “PN-low” subgroups (≥ and Results: PN levels decreased on DPL vs PBO. Both DPL q2w regimens significantly reduced the rates of severe exacerbation in both PN-high and PN-low subgroups vs PBO. On PBO, the rate of exacerbation was 2-fold higher in PN-high vs PN-low pts. Conclusions : Dupilumab treatment, 200 and 300 mg q2w, reduces serum PN and the risk of severe exacerbation in both the more-frequently exacerbating PN-high and less-frequently exacerbating PN-low asthma pts.