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The effects of an anti-CD11a mAb, efalizumab, on allergen-induced airway responses and airway inflammation in subjects with atopic asthma.

AbstractBACKGROUND:
Efalizumab is a humanized IgG(1) mAb against the lymphocyte function antigen-1 (LFA-1) alpha chain, CD11a. Blocking of LFA-1/intercellular adhesion molecule interactions could inhibit asthmatic inflammation by blocking adhesion and activation of LFA-1-positive leukocytes.
OBJECTIVE:
A randomized, double-blinded, placebo-controlled, parallel group, multicenter study investigated the effects of efalizumab on allergen-induced airway responsiveness and airway inflammation.
METHODS:
Thirty-five nonsmoking subjects with mild allergic asthma were randomized to receive efalizumab (n = 24) or placebo (n = 11) in 8 weekly subcutaneous doses (0.7 mg/kg conditioning dose followed by 7 weekly doses of 2.0 mg/kg). Allergen challenges were performed at screening and after 4 and 8 weeks of treatment. Samples of sputum (n = 18 subjects) and blood (n = 35 subjects) were collected the day before challenges, and sputum was collected again at 7 and 24 hours after each challenge. Nonparametric tests were used to compare allergen-induced differences between efalizumab and placebo groups.
RESULTS:
Subjects receiving efalizumab developed headache (48%) and flu syndrome (28%) compared to subjects receiving placebo (0%). After 8 weeks of efalizumab, the maximum late percent fall in FEV(1) (late asthmatic response) was inhibited by 50%, but neither the late response nor the late area under the curve was statistically different than placebo (P =.098 and.062, respectively). Efalizumab had no effect on the maximum early percent fall in FEV(1) (early asthmatic response) or early area under the curve compared to placebo (P >.59). Efalizu-mab significantly reduced the postallergen increase in sputum EG2-positive cells and metachromatic cells (P <.05). No other comparisons were statistically different.
CONCLUSIONS:
Blocking of LFA-1/intercellular adhesion module interactions by efalizumab inhibits the development of allergen-induced cellular inflammatory responses measured in induced sputum and might attenuate the late asthmatic response. Larger studies are needed to confirm this.
AuthorsGail M Gauvreau, Allan B Becker, Louis-Philippe Boulet, Jamila Chakir, Robert B Fick, William L Greene, Kieran J Killian, Paul M O'byrne, John K Reid, Donald W Cockcroft
JournalThe Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 112 Issue 2 Pg. 331-8 (Aug 2003) ISSN: 0091-6749 [Print] United States
PMID12897739 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Blood Proteins
  • CD11a Antigen
  • Eosinophil Granule Proteins
  • Ribonucleases
  • efalizumab
Topics
  • Adult
  • Antibodies, Monoclonal (adverse effects, immunology, therapeutic use)
  • Antibodies, Monoclonal, Humanized
  • Asthma (complications, drug therapy, etiology, pathology, physiopathology)
  • Blood Proteins (metabolism)
  • Bronchial Hyperreactivity (drug therapy, etiology)
  • Bronchitis (drug therapy, etiology)
  • CD11a Antigen (immunology)
  • Double-Blind Method
  • Eosinophil Granule Proteins
  • Female
  • Forced Expiratory Volume (drug effects)
  • Humans
  • Hypersensitivity (complications)
  • Male
  • Middle Aged
  • Ribonucleases
  • Sputum (cytology, metabolism)

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