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FDA Approves Omalizumab (Xolair), a Recombinant Anti-IgE Antibody, to Treat Moderate to Severe Allergic Asthma For Professionals Hot Topics articles are provided by AAAAI as a service to its members for educational and informational purposes only. They are provided solely on an "as is" basis and any use or reliance on the information contained in such articles is solely at the user's risk. Hot Topics articles are not intended to serve as the primary basis for making medical decisions. These articles are prepared and reviewed by AAAAI members and reflect the opinions of the author(s) and do no necessarily represent the opinions or positions of AAAAI. As with all such resources, these articles reflect medical science at the time they are written; AAAAI assumes no responsibility to update these articles or to remove them from its web site as future developments occur. DateJune 23, 2003 Background Omalizumab (Xolair) is a recombinant humanized monoclonal anti-IgE antibody that binds to IgE on the same Fc site as Fc R1. Omalizumab causes a reduction in total serum IgE in atopic patients, which attenuates the amount of antigen-specific IgE that can bind to and sensitize tissue mast cells and basophils. This, in turn, leads to a decrease in symptoms of allergic diseases. The monoclonal antibody contains 5% murine sequences (needed for the IgE binding portion) and 95% human residues from a human IgG 1 kappa framework. Omalizumab reduces the amount of free IgE (the unbound form present in the circulation) available to bind to Fc R1 receptors and results in a reduction in the expression of high affinity IgE receptors. Omalizumab does not bind to IgE already bound to effector cells. Study Results Phase II studies with omalizumab indicated it was safe and effective for the treatment of allergic asthma. Three pivotal Phase III studies enrolled participants 6 to 75 years of age who had allergic asthma. Xolair is indicated for adults and adolescents (12 years of age and above) so we will focus only on two pivotal studies involving that population. In these studies, 1071 patients (542 who received omalizumab) with allergic asthma who were symptomatic despite daily treatment with orally inhaled BDP (420 to1680 mcg/day) were enrolled. Omalizumab dosing was tailored to baseline body weight and serum IgE levels (.016 mg/kg/IgE [IU/mL]). These trials consisted of four phases: a run-in phase of four to six weeks prior to randomization; a steroid stable phase of sixteen weeks during which participants received omalizumab or placebo added to their standard BDP dose; a steroid withdrawal phase of twelve weeks with an attempt to reduce steroids by 25% every two weeks; and a five month extension safety period. During the steroid stable phase in the omalizumab group, the mean number of asthma exacerbations per patient was reduced to 48 - 58% of that in the placebo group and the proportion of patients experiencing one or more asthma exacerbations was reduced to 37 - 58% of that in the placebo group. In addition, there was a significant improvement in asthma symptom scores and albuterol rescue use. After 16 weeks of treatment, the median percent reduction in the dose of BDP was significantly greater in the omalizumab-treated than placebo-treated patients (75 - 83% vs. 50%). Twice as many patients were able to completely withdraw BDP (approximately 40% vs. 20%). During the steroid withdrawal phase, the number of asthma exacerbations in the omalizumab group was significantly less than those in the placebo group. Omalizumab improved standard symptom scores, quality of life and pulmonary functions as well as reduced the frequency of urgent care visits. Adverse event profiles were similar in omalizumab and placebo-treated patients. In addition to these two pivotal Phase III studies, data from 6 - 11 year old children and adolescents and adults with more severe asthma also favored omalizumab. In other trials omalizumab has also been shown to be effective in allergic rhinitis. Discussion This therapy represents a new approach in the use of immunomodulators aimed at critical steps in the pathogenesis of allergic diseases. Its use should be limited to those patients with moderate to severe persistent allergic asthma who: 1) are inadequately controlled with appropriate combination therapy; 2) have complications due to inhaled or oral corticosteroid use; 3) have increased need for urgent care, emergency department or inpatient services due to asthma exacerbations; 4) have significant impairment in activities of daily living; or 5) have unresolved adherence issues. Omalizumab should be administered every two to four weeks by subcutaneous injection based on body weight and total serum IgE levels. Omalizumab should not be used off label until appropriate dosages and adverse event potential are adequately assessed. Bottom Line Synopsis Omalizumab is a new addition to the armamentarium of agents available for the treatment of patients with moderate to severe persistent asthma. Patients require an appropriate evaluation by a specialist (allergist/immunologist, pulmonologist or PCP with specific interests and experience in asthma). There is a critical need for communication among physicians administering omalizumab, patients and their primary care physicians. It may offer benefits in patients with high-risk asthma. Disclosure Author: Dr. Thomas B. Casale is a consultant for both Novartis and Genentech, and has been an investigator in omalizumab studies sponsored by Novartis and Genentech. Reviewed by:
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