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Daclizumab Improves Asthma Control in Patients with Moderate to Severe Persistent Asthma

A Randomized, Controlled Trial

¹ Section of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; ² Brigham and Women's Hospital, Boston, Massachusetts; ³ National Jewish Medical and Research Center, Denver, Colorado; ⁴ Allergy, Asthma, and Dermatology Research Center, Lake Oswego, Oregon; ⁵ Cough and Sinus Center, Aurora Advanced Healthcare, Inc., Milwaukee, Wisconsin; ⁶ PDL BioPharma, Inc., Redwood City, California

Correspondence and requests for reprints should be addressed to William W. Busse, M.D., University of Wisconsin School of Medicine and Public Health, J5/219 CSC, Box 2454, 600 Highland Ave., Madison, WI 53792. E-mail wwb{at}medicine.wisc.edu

Rationale: Airway inflammation in asthma is associated with increased activated CD25⁺ T cells, IL-2, and soluble IL-2 receptors (IL-2Rs).

Objectives: 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 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.

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 β₂-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).

Key Words: pulmonary function • asthma • daclizumab • airway inflammation

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Daclizumab is a humanized monoclonal antibody that binds specifically to the (Tac, CD25) subunit of the high-affinity IL-2R, and inhibits IL-2 binding and its biological activity. However, there is limited information concerning potential benefits of daclizumab in asthma. What This Study Adds to the Field The use of daclizumab, an anti-CD25 antibody, in patients with moderate to severe asthma was associated with a small improvement in lung function and asthma control along with a reduction in blood eosinophils.

 

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