|
||||||||||||||
 |
||||||||||||||
|
Allied Health: Articles of Interest Right drug at right time for moderate to severe allergic asthmatics Xolair (Omalizumab) is the newest and the most revolutionary new drug for the treatment of moderate and severe asthmatic patients. It was introduced over a year ago in which clinical studies evaluated the efficacy and safety of Xolair in patients with the primary goal of reducing exacerbations. Before Xolair was introduced, the only drugs that a severe asthmatic could take only addressed the symptoms. In allergic asthma, exacerbations can occur when immunoglobulin E (IgE) molecules bound to Fce-RI receptors on mast cells are cross-linked by an allergen. The mast cell then degranulates, releasing inflammatory mediators such as histamine, leukotrienes, and tumor necrosis factor alpha, which cause the symptoms of asthma. Xolair (Omalizumab) is a recombinant DNA-derived humanized IgGk monoclonal antibody that selectively binds to human immunoglobulin E (IgE). Xolair inhibits the binding of IgE to the high-affinity IgE receptor (FceRI) on the surface of the mast cells and basophils. Reduction in surface-bound IgE on the high affinity receptor bearing cells limits the degree of release of mediators of the allergic response. It should also be noted that Xolair can reduce the number of FceRI receptors on basophils in atopic patients. The bottom line is that Xolair interrupts the allergic-inflammatory cascade in IgE-mediated asthma. Xolair is indicated for the moderate to severe persistent asthmatic patient who is 12 and older, has a positive skin test or in-vitro reaction to a perennial aeroallergen, and does not have control of their symptoms with inhaled corticosteroids. It has a pregnancy category B that is very unusual for an asthma medicine. Clinical studies have shown that serum-free IgE levels were reduced by 96% within one hour after using the proper dosing requirements (total serum IgE level and body weight). Xolair has arrived just in time for the 17 million asthmatics in the United States. This number is expected to rise to an alarming rate, with emergency rooms across the nation seeing 2 million asthma visitors a year.1 Along with the high number of emergency room visits, related hospitalizations statistics are close to 500,000.2 All of these numbers equal a depressing figure of 5,000 deaths related to asthma.3 The direct cost of asthma is approximately $9.4 billion, and the indirect costs are $4.6 billion.4 Between late 70’s to the mid 90’s, mortality more than doubled with this hard-to-treat disease state.5 Xolair was approved by the FDA based on two pivotal clinical trials in moderate to severe asthmatics. The purpose of these trials was to determine if Xolair would reduce exacerbations compared to the placebo group. One study was written by William W. Busse, MD, FAAAAI and colleagues, and entitled Omalizumab, Anti-IgE Recombinant Humanize Mononclonal Antibody, for the Treatment of Severe Allergic Asthma. It appeared in the Journal of Allergy and Clinical Immunology in 2001. The second study was published in the European Respiratory Journal in 2001 by Dr. M. Soler, et al. entitled The Anti- IgE Antibody Omalizumab Reduces Exacerbations and Steroid Requirements in Allergic Asthmatics. Both pivotal studies were randomized, double-blind, placebo-controlled and multi-center, and involved a parallel group. It was Omalizumab versus placebo and both were administered subcutaneously. All study patients, totaling 1,071, were adults and adolescents with moderate to severe persistent asthma with a positive persistent skin test, and treated with inhaled corticosteroids and rescue medications when appropriate. Omalizumab dosing is based on the level of IgE between 30 to 700 (IU/mL) and body weight of 30 to 150 (kg). There was a 4-to-6 week run-in phase that was for the beclomethasone dipropionate conversion to Omalizumab or placebo. There was an initial phase of the study included a 28-week core evaluation, and was divided into a stable steroid phase at 16 weeks and a steroid reduction phase at 12 weeks. In the steroid reduction phase beclomethasone dipropionate was reduced by 25% every two weeks. The primary endpoints for these two studies were the reduction of exacerbations, defined as worsening of asthma requiring systemic corticosteroids treatment or doubling the inhaled corticosteroid dose from baseline. Both studies provided results of the actual reduction of exacerbations per patient treated with Xolair compared to placebo. In both the stable steroid phase and the steroid reduction phase, exacerbations were reduced between 33% to 75%. When reviewing the studies collectively, the need of beclomethasone dipropionate was reduced by 100% in 41.3% of the patient population studied. There was a 24-week extension of the above trials, authored by Bobby Q. Lanier, MD, FAAAAI and colleagues, that was published in the August 2003 edition of Annals of Allergy, Asthma, and Immunology. During this extension phase, patients were allowed to use other asthma medications, and the investigators were allowed to switch from BDP to other inhaled corticosteroids when necessary. The bottom line to the 24-week extension study confirmed the findings of the original two studies outlined above. In the moderate to severe asthmatic patient, long-term Xolair treatment reflected a reduction in the frequency of exacerbations while reducing the need of their initial asthma medication and/or inhaled corticosteroids. Safety of the drug over one year of complete treatment was reported as excellent. There was a 28% mean exacerbation reduction in the Xolair patient population compared to the placebo group. This finding is remarkable based on the fact the Xolair-treated patients maintained a lower dose of inhaled corticosteroids. In fact, 33% of patients within the Xolair group completed the extension trial without the need of inhaled corticosteroids, compared to 10% within the placebo group. As it relates to this extension trial, Dr. C.E. Owen reported an interesting relation to lung function in Pulmonary Pharmacology Therapeutics in 2002. Owen stated that overall, the improvement in lung function with Omalizumab was consistent with its anti-inflammatory effects attributable to suppression of free IgE levels. This is an important note because in the placebo-treated patients their use of long-acting bronchodilators was higher than the Xolair patient arm of the trial. The adverse reactions most commonly reported with Xolair were injection site reaction (45%), viral infections (23%), upper respiratory tract infection (20%), sinusitis (16%) headache (15%) and pharyngtis (11%). Two warnings that occurred in clinical studies with Xolair are malignancies and anaphylaxis. The observed incidence of malignancies among Xolair treated patients ( 0.5%) was numerically higher but was not a statistical significant event compared to the controlled group (0.2%). Anaphylactic reactions were rare but temporally associated with Xolair administration. Footnotes
|
|||||||||||||
|
© 1996-2008 · All Rights Reserved · American Academy of Allergy Asthma & Immunology |
||||||||||||||
