Lebrikizumab (LEB) was studied for treating immune mediated disorders, including asthma and atopic dermatitis. LAVOLTA I (NCT01867125) and II (NCT01868061) (LI&LII) were duplicate randomized, placebo-controlled Phase 3 LEB trials in uncontrolled asthma that enrolled subjects irrespective of asthma exacerbation history, baseline blood eosinophilia, or FeNO. LI&II failed to show consistently significant results in asthma exacerbation rate reduction. Here, effects of LEB on inflammatory biomarkers were assessed in patients with asthma. Serum samples were tested using immunoassays for periostin (IL-13 activation marker), CCL13 (driver of chemotaxis in immune cells), CCL17 (driver of chemotaxis in Th2 cells), and IgE (hallmark of allergic inflammation). Mean changes from baseline in these markers are reported and change from baseline comparisons were evaluated using MMRM with different contrasts. Within-biomarker multiplicity controls were performed. In LI, for 125mg LEB Q4W (N=359) vs placebo Q4W (N=362) at week 1, reductions from baseline were -35.6 vs -1.7 pg/mL for CCL13; -59.3 vs -4.6 pg/mL for CCL17; and -5.3 vs -1.2 ng/mL for periostin; and week 12 reductions from baseline were -49.5 vs -8.8 IU/mL for IgE. Differences with 125mg LEB Q4W were significant (p <0.0001), differences with placebo were not. Similar reductions were seen for LEB 37.5mg Q4W and for LII. Reductions were maintained during the 52-week LI&LII treatment periods. LEB treatment decreased inflammatory biomarkers in asthma. Reductions in circulating inflammatory biomarkers were observed as early as 1 week following a single LEB dose. Improvements in inflammation were maintained during 52 weeks of LEB treatment.