Vol. 14 •Issue 10 • Page 27
Anti-IgE Monoclonal Antibody Cuts Risk of Serious Asthma Exacerbations
By Wayne Kuznar
NEW ORLEANS–A recombinant humanized monoclonal antibody directed against immunoglobulin E (IgE) can permit sustained reductions in the use of inhaled corticosteroids and reduce the incidence of asthma exacerbations in patients with allergic asthma, investigators reported at the 57th annual meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI) held here earlier this year.
Immunoglobulin E is an important mediator of airway inflammation in asthma. Data from phase III studies demonstrated that monthly or twice monthly injections of omalizumab (Xolair) reduced the risk of serious asthma exacerbations requiring hospitalization in both children and adults with moderate to severe allergic asthma.
“It remains to be defined exactly where omalizumab will take its place in asthma care, but it certainly looks like a drug that can prevent severe exacerbations and will, therefore, be an important drug for patients with serious allergic asthma,” said Jonathon Corren, MD, lead author of a pooled analysis of data presented at AAAAI.
The analysis included two double-blind, placebo-controlled trials that enrolled 1,017 patients between 12 to 75 years old who had moderate to severe allergic asthma despite treatment with beclomethasone dipropionate. In the studies, patients received either omalizumab injections every 2 or 4 weeks (the frequency is based on serum IgE levels and body weight) or placebo.
DOSAGES IN STUDY
Dosages of inhaled corticosteroids remained the same for the first 16 weeks, were subsequently reduced over the following eight weeks and then maintained at the lowest tolerated dosage for another four weeks. Patients were followed for another 24 weeks at their minimum effective beclomethasone dosage, giving a total of one year of treatment.
Hospitalizations due to a serious asthma exacerbation were reduced from 2.5 percent in the placebo group to 0.4 percent in the omalizumab group (p = 0.003). Furthermore, omalizumab recipients were able to taper their corticosteroid use by 80 to 90 percent, while placebo recipients reduced it only 50 percent.
“In the omalizumab group, 40 percent of patients were able to get off steroids completely,” said Corren, medical director, Allergy Research Foundation, and associate clinical professor of medicine at the University of California-Los Angeles. “What’s important is that patients had fewer exacerbations at the same time they were able to taper to a lower dose of steroids.”
In another study of 334 children with moderate to severe allergic asthma who required beclomethasone, hospitalizations by week 28 due to a serious asthma exacerbation were reduced from 4.6 percent in placebo recipients to zero percent in the omalizumab-treated group (p = 0.003).
“Omalizumab has been shown to bind to IgE that is free in the serum but does not bind to IgE on mast cells,” said Corren. “This is an important distinction because it doesn’t have the ability to activate mast cells and cause allergic reactions or anaphylaxis. It also does not bind complement and, therefore, will not cause immune complex disease.”
These findings were confirmed in a multinational, randomized, double-blind, parallel group trial presented by Roland Buhl, MD. In the study, 546 adults with allergic asthma who were symptomatic despite treatment with beclomethasone and albuterol were randomized to subcutaneous omalizumab, administered every two or four weeks, or placebo.
After 16 weeks of stable treatment, a reduction in the beclomethasone dosage was attempted to reach a minimum effective dosage. Patients who successfully completed the 28-week core phase were then entered into a 26-week extension phase.
Some 43 percent of the omalizumab group completed the core phase having their beclomethasone dosage reduced to zero, compared with only 19.5 percent of the placebo group.
“In the long run, one in three omalizumab-treated patients were completely able to avoid inhaled corticosteroids,” said Buhl, director, pulmonary division, Mainz University Hospital, Mainz, Germany. Only 11 percent of the placebo recipients completed the extension phase without any inhaled or oral corticosteroid treatment.
In conjunction with the reduction in corticosteroid use, disease control was sustained in patients treated with omalizumab, as evidenced by a lower incidence of asthma exacerbations in the omalizumab group vs. the placebo group in both the core and extension periods.
“Not knowing how much this medication will cost, I think we will start using it in patients who are not completely controlled by their current medication,” said Buhl. “I may use it initially in patients who do not tolerate inhaled corticosteroids and those who have not only asthma or allergic rhinitis but gastrointestinal symptoms as well.”
In a study of patients with perennial allergic rhinitis, omalizumab was shown to reduce the severity of nasal symptoms in patients who hadn’t responded previously to nasal steroids or immunotherapy, reported Paul Chervinsky, MD, medical director, New England Clinical Studies, North Dartmouth, Mass.
“Omalizumab will probably be used in patients with severe allergic rhinitis who haven’t responded to antihistamines, especially children,” said Chervinsky. “In adults, it will probably be reserved for patients in whom antihistamines and intranasal steroids have failed, although there is a group of patients who resist using intranasal steroids at all because they find them unpleasant or have uncomfortable side effects.”
Wayne Kuznar is a freelance medical writer.