title: Efficacy and safety of an anti-IL-13 mAb in patients with severe asthma: a randomized trial.
abstract: BACKGROUND
  Approximately 5% to 10% of asthmatic patients achieve incomplete symptom control on current therapies. The association of IL-13 with asthma pathology and reduced corticosteroid sensitivity suggests a potential benefit of anti-IL-13 therapy in refractory asthma. GSK679586, a humanized mAb, inhibits IL-13 binding to both IL-13 receptor α1 and α2.
  
  
  OBJECTIVE
  We sought to evaluate the efficacy and safety of GSK679586 in patients with severe asthma refractory to maximally indicated doses of inhaled corticosteroids.
  
  
  METHODS
  Patients who remained symptomatic (Asthma Control Questionnaire score ≥1.5) after uptitration to 1000 μg/d fluticasone propionate or greater were randomized to 3 once-monthly intravenous infusions of 10 mg/kg GSK679586 (n = 99) or placebo (n = 99).
  
  
  RESULTS
  Treatment differences in adjusted mean change from baseline over 12 weeks were nonsignificant for Asthma Control Questionnaire symptom scores (the primary end point; GSK679586 = -0.31, placebo = -0.17, P = .058) and FEV₁ (GSK679586 = -0.01, placebo = 0.03, P = .276). Similar analyses in patients with increased serum IgE levels, blood eosinophil counts, or both were also negative. Incidence of asthma exacerbations was similar between treatments. Most adverse events were nonserious and unrelated to treatment. Two GSK679586-treated patients had treatment-related serious adverse events (lethargy and supraventricular extrasystoles).
  
  
  CONCLUSIONS
  Although well tolerated, GSK679586 did not demonstrate clinically meaningful improvements in asthma control, pulmonary function, or exacerbations in patients with severe asthma. Further studies are needed to determine whether therapies targeting IL-13, the functionally related IL-4 cytokine, or both can provide clinical benefit in patients with severe refractory asthma or a subpopulation of these patients beyond that achievable with high-dose corticosteroids.
authors.affiliation: Alternative Discovery and Development, GlaxoSmithKline, King of Prussia, Pa. Electronic address: erika.h.deboever@gsk.com.
authors.forename: Erika H
authors.initials: EH
authors.lastname: De Boever
authors.affiliation: Biopharm Research, GlaxoSmithKline, Stevenage, United Kingdom.
authors.forename: Claire
authors.initials: C
authors.lastname: Ashman
authors.affiliation: Respiratory Discovery Medicine, GlaxoSmithKline, Stevenage, United Kingdom.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Cahn
authors.affiliation: Respiratory Medicines Development, GlaxoSmithKline, Research Triangle Park, NC.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Locantore
authors.affiliation: II/Biopharm Clinical Statistics, GlaxoSmithKline, Stevenage, United Kingdom.
authors.forename: Phil
authors.initials: P
authors.lastname: Overend
authors.affiliation: Clinical Pharmacology Modeling and Simulation, GlaxoSmithKline, Middlesex, United Kingdom.
authors.forename: Isabelle J
authors.initials: IJ
authors.lastname: Pouliquen
authors.affiliation: Genentech, Research and Early Development, San Francisco, Calif.
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Serone
authors.affiliation: Biopharm Research, GlaxoSmithKline, Stevenage, United Kingdom.
authors.forename: Tracey J
authors.initials: TJ
authors.lastname: Wright
authors.affiliation: Emerging Markets R&D, GlaxoSmithKline, Brentford, United Kingdom.
authors.forename: Mair M
authors.initials: MM
authors.lastname: Jenkins
authors.affiliation: ISP Pharma, Birmingham, United Kingdom.
authors.forename: Inderpal S
authors.initials: IS
authors.lastname: Panesar
authors.affiliation: Global Medical Safety, Janssen Pharmaceuticals, High Wycombe, United Kingdom.
authors.forename: Sivayogan S
authors.initials: SS
authors.lastname: Thiagarajah
authors.affiliation: Asthma Institute, University of Pittsburgh Medical Center, Pittsburgh, Pa.
authors.forename: Sally E
authors.initials: SE
authors.lastname: Wenzel
mesh_terms: D000328:Adult; D018927:Anti-Asthmatic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D018793:Interleukin-13 / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018927:Anti-Asthmatic Agents; D000911:Antibodies, Monoclonal; D018793:Interleukin-13
keywords: IL-13; IL13Rα1; IL13Rα2; efficacy; pharmacodynamics; pharmacokinetics; safety