By Chris Berrie
BERLIN -- October 6, 2008 -- Omalizumab, a recombinant humanised monoclonal antibody, significantly reduces rates of clinically significant asthma exacerbations in ex-smokers with moderate to severe allergic asthma compared with placebo, according to an analysis of 5 multicentre, randomised, double-blind, placebo-controlled, parallel-group, phase 3 studies.
These effects are similar to those for nonsmokers with allergic asthma, researchers said in a presentation here on October 6 at the European Respiratory Society (ERS) 18th Annual Congress.
Principal investigator David Price, MD, Primary Care Respiratory Medicine, Department of General Practice and Primary Care, University of Aberdeen, Aberdeen, United Kingdom, presented the research.
"We are learning that different asthma therapies behave differently in the presence of smoking and other risk factors, so we are looking at whether that impacts on the efficacy of any individual treatment," Dr. Price explained.
In their analysis, Dr. Price and colleagues focussed on whether omalizumab is effective in ex-smokers versus nonsmokers.
Also, omalizumab is designed to selectively bind human immunoglobulin E (IgE), and in this way to prevent the allergic reaction cascade. Therefore, Dr. Price and his team aimed to assess the impact of former smoking status on clinically significant exacerbation rates among patients with moderate to severe persistent IgE-mediated allergic asthma.
Inclusion criteria were asthma duration of 1 year or more, total serum IgE levels between 30 and 700 IU/mL, a relevant positive skin-prick test, and regular treatment with moderate to high doses of inhaled corticosteroids and/or long-acting beta2-agonists.
Ex-smokers were defined as those who smoked within 2 years of their first visit or who had a smoking history of 10 pack years or more.
Omalizumab dosing was at least 0.016 IU/mL every 4 weeks, or 0.008 IU/mL every 2 weeks, with doses calculated according to patient body weight and baseline IgE level.
Primary outcome was the rate of clinically significant asthma exacerbations at week 24. Secondary clinical outcomes were rate of severe asthma exacerbations and least squares mean change from baseline in percent predicted forced expiratory volume at 1 second (FEV1) at 52 weeks.
The analysis included ex-smokers (282 placebo and 268 omalizumab) and nonsmokers (818 placebo and 868 omalizumab). Mean age of patients in the 4 groups ranged from 39 to 45 years, and men made up about 40% to 46% of the groups.
Baseline mean serum total IgE values for these groups were 200.4 and 201.8 IU/mL for ex-smokers and 212.7 and 216.5 IU/mL for nonsmokers. Percent predicted FEV1 values were 70.7% and 69.6% for ex-smokers, and 69.8% and 69.0% for nonsmokers.
Exacerbation rates in the 24 weeks of treatment were significantly lower in the omalizumab group compared with placebo for both ex-smokers (0.85 vs 1.29; P = .004) and nonsmokers (0.83 vs 1.37; P < .001).
The same was seen for severe exacerbation rates after 52 weeks (0.24 vs 0.51; 0.22 vs 0.40; respectively; P < .001 for each).
Both groups saw statistically significant changes from baseline for percent predicted FEV1, compared with placebo (1.97, P = .039; 2.30, P < .0001; respectively).
Dr. Price said, "There is absolutely no clinically significant difference that we could find in the efficacy [of omalizumab] between these 2 populations."
Funding for this study was provided by Novartis Pharma AG.
[Presentation title: Omalizumab (Xolair) Reduces Exacerbations in Patients With Moderate-to-Severe Persistent Allergic Asthma Independent of Former Smoking Status. Abstract P2009]
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