Abstract
Numerous recombinant therapies are being investigated for the treatment of asthma. This report reviews the current status of several of these novel agents. Anti-immunoglobulin (Ig)E (omalizumab, Xolair) markedly inhibits all aspects of the allergen challenge in subjects who have reduction of free serum IgE to undetectable levels. Several clinical studies in atopic asthma have demonstrated benefit by improved symptoms and lung function and a reduction in corticosteroid requirements. Early use in atopic asthmatics may be even more effective. Several approaches target interleukin (IL)-4. Soluble IL-4 receptor has been shown to effectively replace inhaled corticosteroid; further studies are under way. Recombinant anti-IL-5 and recombinant IL-12 inhibit blood and sputum eosinophils and allergen-induced eosinophilia without any effect on airway responsiveness, allergen-induced airway responses, or allergen-induced airway hyperresponsiveness. Efalizumab, a recombinant antibody that inhibits lymphocyte trafficking, is effective in psoriasis. A bronchoprovocation study showed a reduction in allergen-induced late asthmatic response and allergen-induced eosinophilia, which suggests that it should be effective in clinical asthma. These exciting novel therapies provide not only promise of new therapies for asthma but also valuable tools for investigation of asthma mechanisms.
Highlights
IgE antibody was identified as the cause of atopic sensitization and atopic allergic reactions about 35 years ago.[6]
Omalizumab administered intravenously at a standard dose of 0.5 mg/kg/wk proved to be very effective in inhibition of the early asthmatic response (EAR) and the late asthmatic response (LAR).[19,20]
We demonstrated a marked and early shift of the allergen PC15 as early as 4 weeks.[20]
Summary
IgE antibody was identified as the cause of atopic sensitization and atopic allergic reactions about 35 years ago.[6]. The allergen challenge model is a useful method to study asthma pharmaceutical agents.[18] This would be true for an agent designed to prevent IgE-mediated airway allergic responses.
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