Published ahead of print on September 11, 2008, doi:10.1164/rccm.200708-1200OC Am. J. Respir. Crit. Care Med., Volume 178, Number 10, November 2008, 1002-1008 A more recent version of this article appeared on November 15, 2008
Submitted on August 14, 2007 Daclizumab Improves Asthma Control in Patients with Moderate to Severe Persistent AsthmaWilliam W Busse1*,1 Section of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA, 2 Brigham and Women's Hospital, Boston, MA, USA, 3 National Jewish Medical and Research Center, Denver, CO, USA, 4 Allergy, Asthma and Dermatology Research Center, Lake Oswego, OR, USA, 5 Cough and Sinus Center, Aurora Advanced Healthcare, Inc., Milwaukee, WI, USA, 6 PDL BioPharma, Inc., Redwood City, CA, USA * To whom correspondence should be addressed. E-mail: wwb{at}medicine.wisc.edu.
Rationale: Airway inflammation in asthma is associated with increased activated CD25+ T cells, interleukin-2 (IL-2), and soluble IL-2 receptors.
Objectives: A randomized, double-blinded, placebo-controlled study evaluated the safety and efficacy of daclizumab, a humanized IgG1 monoclonal antibody against the IL-2 receptor Key words: Pulmonary function; asthma; daclizumab; airway inflammation
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-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 (TAA). Patients dependent on ICS were randomized (3:1) to daclizumab (loading dose 2 mg/kg IV, then 1 mg/kg IV) 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 study drug and were followed for 16 weeks off study drug.
Measurements and Main 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 FEV1 (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 
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 daclizumab-treated patients.
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 pro-inflammatory cytokine generation by IL-2 receptor blockade in activated T cells.
Clinical Trials Registry Information: ID#NCT00028288 registered at www.clinicaltrials.gov
