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: T B Casale, I L Bernstein, W W Busse, C F LaForce, D G Tinkelman, R R Stoltz, R J Dockhorn, J Reimann, J Q Su, R B Fick Jr, D C Adelman
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 100 Issue 1 Pg. 110-21 (Jul 1997) ISSN: 0091-6749 [Print] United States
• PMID: 9257795 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Anti-Idiotypic
• Antibodies, Monoclonal
• Recombinant Fusion Proteins
• anti-IgE antibodies
• Immunoglobulin E

Topics

• Adolescent
• Adult
• Aged
• Animals
• Antibodies, Anti-Idiotypic (adverse effects, therapeutic use)
• Antibodies, Monoclonal (adverse effects, pharmacokinetics, pharmacology)
• Antibody Specificity
• Demography
• Double-Blind Method
• Female
• Humans
• Immunization, Passive (adverse effects)
• Immunoglobulin E (immunology)
• Male
• Mice
• Middle Aged
• Poaceae (immunology)
• Pollen (immunology)
• Recombinant Fusion Proteins (adverse effects, immunology, therapeutic use)
• Rhinitis, Allergic, Seasonal (etiology, immunology, therapy)
• Severity of Illness Index
• Skin Tests
• Titrimetry