title: The effects of an anti-CD11a mAb, efalizumab, on allergen-induced airway responses and airway inflammation in subjects with atopic asthma.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Medicine, McMaster University, Health Sciences Centre, Hamilton, ON, Canada.
authors.forename: Gail M
authors.initials: GM
authors.lastname: Gauvreau
authors.forename: Allan B
authors.initials: AB
authors.lastname: Becker
authors.forename: Louis-Philippe
authors.initials: LP
authors.lastname: Boulet
authors.forename: Jamila
authors.initials: J
authors.lastname: Chakir
authors.forename: Robert B
authors.initials: RB
authors.lastname: Fick
authors.forename: William L
authors.initials: WL
authors.lastname: Greene
authors.forename: Kieran J
authors.initials: KJ
authors.lastname: Killian
authors.forename: Paul M
authors.initials: PM
authors.lastname: O'byrne
authors.forename: John K
authors.initials: JK
authors.lastname: Reid
authors.forename: Donald W
authors.initials: DW
authors.lastname: Cockcroft
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001249:Asthma / Q000150:complications / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D001798:Blood Proteins / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000209:etiology; D001991:Bronchitis / Q000188:drug therapy* / Q000209:etiology; D040881:CD11a Antigen / Q000276:immunology*; D004311:Double-Blind Method; D047091:Eosinophil Granule Proteins; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D006967:Hypersensitivity / Q000150:complications*; D008297:Male; D008875:Middle Aged; D012260:Ribonucleases; D013183:Sputum / Q000166:cytology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001798:Blood Proteins; D040881:CD11a Antigen; D047091:Eosinophil Granule Proteins; D012260:Ribonucleases; C472181:efalizumab