title: Use of an anti-IgE humanized monoclonal antibody in ragweed-induced allergic rhinitis.
abstract: BACKGROUND
  Increased serum levels of antigen-specific IgE are often associated with allergic respiratory disorders. RhuMAb-E25, a recombinant humanized monoclonal antibody, decreases free serum IgE by forming biologically inactive immune complexes with free IgE.
  
  
  OBJECTIVE
  We hypothesized that rhuMAb-E25 would decrease total serum IgE and reduce symptoms.
  
  
  METHODS
  Two hundred forty subjects were enrolled into five groups to determine the safety, tolerance, and efficacy of repeated administration of rhuMAb-E25 in adults with ragweed-induced allergic rhinitis and to explore the pharmacodynamic relationship of rhuMAb-E25 and IgE. One hundred eighty-one subjects received an initial intravenous loading dose (day 0, 1 month before ragweed season), followed by administration of rhuMAb-E25 (in mg/kg body weight) of 0.15 mg/kg subcutaneously, 0.15 mg/kg intravenously, or 0.5 mg/kg intravenously on days 7, 14, 28, 42, 56, 70, and 84. A subcutaneous placebo group and an intravenous placebo group were included. The total evaluation time included the 84-day treatment period, followed by a 42-day observation period.
  
  
  RESULTS
  Adverse events were mild, and no differences were observed in the rates between the three active and two placebo treatment groups. Ragweed-specific IgE levels correlated with symptom scores. RhuMAb-E25 decreased serum free IgE levels in a dose- and baseline IgE-dependent fashion. However, only 11 subjects had IgE levels that were suppressed to undetectable levels (< or = 24 ng/ml), a sample too small to demonstrate significant differences and clinical efficacy. Thus the case for efficacy was not proven. Nonetheless, the study confirms that it is safe to repeatedly administer rhuMAb-E25 over a period of months.
  
  
  CONCLUSIONS
  Because rhuMAb-E25 decreased serum free IgE in a dose-dependent fashion and because symptom scores correlated with antigen-specific IgE levels, the results suggest that if given in adequate doses, rhuMAb-E25 should be an effective therapy for allergic diseases.
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, USA.
authors.forename: T B
authors.initials: TB
authors.lastname: Casale
authors.forename: I L
authors.initials: IL
authors.lastname: Bernstein
authors.forename: W W
authors.initials: WW
authors.lastname: Busse
authors.forename: C F
authors.initials: CF
authors.lastname: LaForce
authors.forename: D G
authors.initials: DG
authors.lastname: Tinkelman
authors.forename: R R
authors.initials: RR
authors.lastname: Stoltz
authors.forename: R J
authors.initials: RJ
authors.lastname: Dockhorn
authors.forename: J
authors.initials: J
authors.lastname: Reimann
authors.forename: J Q
authors.initials: JQ
authors.lastname: Su
authors.forename: R B
authors.initials: RB
authors.lastname: Fick
authors.forename: D C
authors.initials: DC
authors.lastname: Adelman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D000918:Antibody Specificity; D003710:Demography; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007116:Immunization, Passive / Q000009:adverse effects; D007073:Immunoglobulin E / Q000276:immunology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D006109:Poaceae / Q000276:immunology; D011058:Pollen / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use*; D006255:Rhinitis, Allergic, Seasonal / Q000209:etiology* / Q000276:immunology / Q000628:therapy*; D012720:Severity of Illness Index; D012882:Skin Tests; D017186:Titrimetry
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D011993:Recombinant Fusion Proteins; C026408:anti-IgE antibodies; D007073:Immunoglobulin E