title: Daclizumab improves asthma control in patients with moderate to severe persistent asthma: a randomized, controlled trial.
abstract: BACKGROUND
  Airway inflammation in asthma is associated with increased activated CD25(+) T cells, IL-2, and soluble IL-2 receptors (IL-2Rs).
  
  
  OBJECTIVE
  A randomized, double-blinded, placebo-controlled study was used to evaluate the safety and efficacy of daclizumab, a humanized IgG1 monoclonal antibody against the IL-2R alpha chain (CD25) of activated lymphocytes, in adults with moderate to severe persistent asthma.
  
  
  METHODS
  Patients with obstructive pulmonary functions, despite inhaled corticosteroids (ICS), were switched to equivalent dose inhaled triamcinolone acetate acetonide (TAA). Patients dependent on ICS were randomized (3:1) to daclizumab (intravenous loading dose, 2 mg/kg, then 1 mg/kg) or placebo every 2 weeks, added to stable-dose TAA through Week 12 (Treatment Period 1). Over Weeks 12-20 (Treatment Period 2), patients tapered TAA while on the study drug, and were followed for 16 weeks off the study drug.
  
  
  RESULTS
  Among 115 evaluable patients (88 daclizumab, 27 placebo), groups had similar age, disease duration, and length of ICS use. During Treatment Period 1, daclizumab improved FEV(1) (daclizumab, 4.4 +/- 1.80% vs. placebo, 1.5 +/- 2.39%; P = 0.05), and reduced daytime asthma symptoms (P = 0.018) and short-acting inhaled beta(2)-agonist use (P = 0.009). Daclizumab treatment prolonged time to exacerbation (P = 0.024). Adverse events were evenly distributed between groups, although there were more serious adverse events in the patients treated with daclizumab.
  
  
  CONCLUSIONS
  Daclizumab improved pulmonary function and asthma control in patients with moderate to severe chronic asthma inadequately controlled on ICS. The mechanism of action likely involves inhibition of proinflammatory cytokine generation by IL-2R blockade in activated T cells. Clinical trial registered with www.clinicaltrials.gov (NCT00028288).
authors.affiliation: Department of Medicine , Section of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA. wwb@medicine.wisc.edu
authors.forename: William W
authors.initials: WW
authors.lastname: Busse
authors.forename: Elliot
authors.initials: E
authors.lastname: Israel
authors.forename: Harold S
authors.initials: HS
authors.lastname: Nelson
authors.forename: James W
authors.initials: JW
authors.lastname: Baker
authors.forename: B Lauren
authors.initials: BL
authors.lastname: Charous
authors.forename: Donald Y
authors.initials: DY
authors.lastname: Young
authors.forename: Vladimir
authors.initials: V
authors.lastname: Vexler
authors.forename: Richard S
authors.initials: RS
authors.lastname: Shames
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D000077561:Daclizumab; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000037:antagonists & inhibitors*; D053645:Interleukin-2 Receptor alpha Subunit; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000188:drug therapy / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D000077561:Daclizumab