title: Lebrikizumab treatment in adults with asthma.
abstract: BACKGROUND
  Many patients with asthma have uncontrolled disease despite treatment with inhaled glucocorticoids. One potential cause of the variability in response to treatment is heterogeneity in the role of interleukin-13 expression in the clinical asthma phenotype. We hypothesized that anti-interleukin-13 therapy would benefit patients with asthma who had a pretreatment profile consistent with interleukin-13 activity.
  
  
  METHODS
  We conducted a randomized, double-blind, placebo-controlled study of lebrikizumab, a monoclonal antibody to interleukin-13, in 219 adults who had asthma that was inadequately controlled despite inhaled glucocorticoid therapy. The primary efficacy outcome was the relative change in prebronchodilator forced expiratory volume in 1 second (FEV(1)) from baseline to week 12. Among the secondary outcomes was the rate of asthma exacerbations through 24 weeks. Patient subgroups were prespecified according to baseline type 2 helper T-cell (Th2) status (assessed on the basis of total IgE level and blood eosinophil count) and serum periostin level.
  
  
  RESULTS
  At baseline, patients had a mean FEV(1) that was 65% of the predicted value and were taking a mean dose of inhaled glucocorticoids of 580 μg per day; 80% were also taking a long-acting beta-agonist. At week 12, the mean increase in FEV(1) was 5.5 percentage points higher in the lebrikizumab group than in the placebo group (P = 0.02). Among patients in the high-periostin subgroup, the increase from baseline FEV(1) was 8.2 percentage points higher in the lebrikizumab group than in the placebo group (P = 0.03). Among patients in the low-periostin subgroup, the increase from baseline FEV(1) was 1.6 percentage points higher in the lebrikizumab group than in the placebo group (P = 0.61). Musculoskeletal side effects were more common with lebrikizumab than with placebo (13.2% vs. 5.4%, P = 0.045).
  
  
  CONCLUSIONS
  Lebrikizumab treatment was associated with improved lung function. Patients with high pretreatment levels of serum periostin had greater improvement in lung function with lebrikizumab than did patients with low periostin levels. (Funded by Genentech; ClinicalTrials.gov number, NCT00930163 .).
authors.affiliation: Allergy Medical Clinic, Los Angeles, California, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Corren
authors.forename: Robert F
authors.initials: RF
authors.lastname: Lemanske
authors.forename: Nicola A
authors.initials: NA
authors.lastname: Hanania
authors.forename: Phillip E
authors.initials: PE
authors.lastname: Korenblat
authors.forename: Merdad V
authors.initials: MV
authors.lastname: Parsey
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Arron
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Harris
authors.forename: Heleen
authors.initials: H
authors.lastname: Scheerens
authors.forename: Lawren C
authors.initials: LC
authors.lastname: Wu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Su
authors.forename: Sofia
authors.initials: S
authors.lastname: Mosesova
authors.forename: Mark D
authors.initials: MD
authors.lastname: Eisner
authors.forename: Sean P
authors.initials: SP
authors.lastname: Bohen
authors.forename: John G
authors.initials: JG
authors.lastname: Matthews
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000627:therapeutic use; D015815:Cell Adhesion Molecules / Q000097:blood; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D018793:Interleukin-13 / Q000037:antagonists & inhibitors* / Q000276:immunology; D008297:Male
chemical_list: D000911:Antibodies, Monoclonal; D001993:Bronchodilator Agents; D015815:Cell Adhesion Molecules; D005938:Glucocorticoids; D018793:Interleukin-13; C512835:POSTN protein, human; C561806:lebrikizumab