Anti-IgE, Airway Inflammation, and Asthma: A Lesson in Pathophysiology
Anti-IgE, Airway Inflammation, and Asthma: A Lesson in Pathophysiology
Fahy JV
J Allergy Clin Immunol. 2006;117:1230-1232
Omalizumab is a humanized recombinant IgG antibody directed against human IgE, and it is the only anti-IgE drug approved for use in human subjects at this time. It binds to IgE at the high affinity receptor site, and pretreatment with omalizumab has been shown to block both the early and late asthmatic response to inhaled allergen.
Studies outlining the effects of omalizumab in phase 2 trials showed a modest effect on asthma symptoms, but a more impressive effect was subsequently found on the incidence of asthma exacerbations. As a result, many phase 3 trials used the incidence of asthma exacerbations as the primary study outcome, with a significant benefit noted in those treated with omalizumab. Those treated with omalizumab have had approximately half the asthma exacerbations compared with those not using the drug.
The surprising outcome of some of these studies has challenged our understanding of the mechanism of asthmatic inflammation. For example, despite demonstrated clinical benefit, omalizumab has not been shown to improve nonspecific bronchial hyperreactivity (BHR) - eg, to methacholine, and also does not have large effects on measured airflow parameters. Treatment with omalizumab, however, has resulted in significant reductions in airway eosinophilia in patients with asthma, similar to those seen in patients treated with corticosteroids. The mechanisms whereby omalizumab may have such a profound effect on asthma exacerbation rates while having only modest effects on bronchial hyperresponsiveness and forced expiratory volume (FEV1) remain somewhat of a mystery.
Anti-IgE: Lessons Learned From Effects on Airway Inflammation and Asthma Exacerbation
Fahy JV
J Allergy Clin Immunol. 2006;117:1230-1232
Summary
Omalizumab is a humanized recombinant IgG antibody directed against human IgE, and it is the only anti-IgE drug approved for use in human subjects at this time. It binds to IgE at the high affinity receptor site, and pretreatment with omalizumab has been shown to block both the early and late asthmatic response to inhaled allergen.
Studies outlining the effects of omalizumab in phase 2 trials showed a modest effect on asthma symptoms, but a more impressive effect was subsequently found on the incidence of asthma exacerbations. As a result, many phase 3 trials used the incidence of asthma exacerbations as the primary study outcome, with a significant benefit noted in those treated with omalizumab. Those treated with omalizumab have had approximately half the asthma exacerbations compared with those not using the drug.
The surprising outcome of some of these studies has challenged our understanding of the mechanism of asthmatic inflammation. For example, despite demonstrated clinical benefit, omalizumab has not been shown to improve nonspecific bronchial hyperreactivity (BHR) - eg, to methacholine, and also does not have large effects on measured airflow parameters. Treatment with omalizumab, however, has resulted in significant reductions in airway eosinophilia in patients with asthma, similar to those seen in patients treated with corticosteroids. The mechanisms whereby omalizumab may have such a profound effect on asthma exacerbation rates while having only modest effects on bronchial hyperresponsiveness and forced expiratory volume (FEV1) remain somewhat of a mystery.