Asthma, Rhinitis, Other Respiratory Diseases
Omalizumab rapidly decreases nasal allergic response and FcεRI on basophils

https://doi.org/10.1016/j.jaci.2003.11.044Get rights and content

Abstract

Background

Omalizumab is a monoclonal anti-IgE antibody that is effective for the treatment of allergic respiratory disorders; however, its onset of action is unknown.

Objective

This study was designed to determine the onset of action of omalizumab through the use of a challenge model to determine time-dependent inhibition of ragweed-induced changes in nasal volume as well as correlate the kinetics of omalizumab-induced decreases in serum free IgE and FcεRI receptors on basophils.

Methods

We conducted a 6-week, randomized, double-blind, placebo-controlled study of 24 rhinitic patients with ragweed allergy. After PD30 ragweed nasal allergen challenge, patients received either omalizumab, ∼0.016 mg/kg per IgE (IU/mL), or placebo at days 0 and 28 and were rechallenged with ragweed PD30 dose biweekly. FcεRI expression on blood basophils was determined by flow cytometry at baseline and 7, 14, 28, and 42 days after treatment. IgE levels were measured at baseline and on days 3, 28, and 42.

Results

Mean IgE levels decreased by 96% (P < .001) from baseline within 3 days in the omalizumab group. Baseline 30% ragweed-induced nasal volume response was decreased to 20.4% at 7 to 14 days (P < .001) and 12.2% at 35 to 42 days (P < .001) for the omalizumab group. There was a median decrease in basophil FcεRI expression of 73% (P < .001) in the omalizumab group, with maximum inhibition occurring within 14 days of treatment. No significant changes in IgE levels, nasal allergen challenge responses, or basophil FcεRI expression were observed throughout the study in the placebo group.

Conclusions

Our study showed that the onset of action by omalizumab in blunting ragweed-induced nasal responses is within 2 weeks, and this response was associated with 2 putative mechanisms of action: decreased serum free IgE and decreased FcεRI receptor expression on immune effector cells.

Section snippets

Subjects

Subjects were between 19 and 50 years of age and had a history of ragweed SAR requiring pharmacotherapy for at least 2 years. All subjects had a positive skin prick test reaction to mixed giant/short/Western ragweed at the screening visit defined by a ragweed-induced wheal at least 5 mm larger in diameter than diluent control and a positive intranasal challenge to ragweed as defined below. Women of childbearing potential had a negative urine pregnancy test result and used effective means of

Demographics

A total of 24 subjects, 16 active and 8 placebo-treated, were enrolled in this single-center study at Creighton University. The mean age for the treated active group was 30.5 years versus 29.4 years for the placebo group. There were 5 men and 11 women in the omalizumab group and 3 men and 5 women in the placebo group. The mean PD30 ragweed dose for the active group was 1.85 AU versus 0.98 AU for the placebo group. The starting IgE level and basophil FcεRI receptor levels were 281 ng/mL and

Discussion

The primary purpose of this study was to determine the onset of action of omalizumab by using a challenge model to better describe how this drug might be used clinically. The second objective of the study was to determine if this clinical end point correlated with immunologic parameters that could explain this onset of action.

We found that omalizumab rapidly inhibited ragweed-induced nasal responses and that this inhibition was seen as early as 7 to 14 days and was even more pronounced by the

Acknowledgments

We thank Mr Bryan Sandlund from Genentech for analysis of the serum-free IgE levels. Hollister-Stier LLC (Spokane, Wash) contributed the mixed giant/short/Western ragweed extracts.

Cited by (256)

View all citing articles on Scopus

Supported by a grant from Genentech, Inc, South San Francisco, California. Basophil flow cytometric analysis was supported by the NIAID Division of Intramural Research, Bethesda, Md.

View full text