Abstract | BACKGROUND: 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.
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Authors | Gail 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 |
Journal | The 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 |
PMID | 12897739
(Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Blood Proteins
- CD11a Antigen
- Eosinophil Granule Proteins
- Ribonucleases
- efalizumab
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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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