Immunoglobulin E Blockade in the Treatment of Asthma
Immunoglobulin E Blockade in the Treatment of Asthma
Patients with moderate-to-severe asthma often have persistent symptoms despite aggressive pharmacotherapy, enthusiastic patient compliance, and proper technique in using delivery devices. Persistent symptoms have detrimental effects on patients' quality of life and result in a tremendous financial burden because of an increased utilization of health care resources. Guidelines from the National Asthma Education and Prevention Program list symptom prevention, near-normal lung function, and participation in activities (e.g., school, work) as goals of successful asthma therapy. The development of pharmacologic and biologic therapies that target different aspects of airway inflammation will help patients with persistent asthma symptoms achieve these goals. Immunoglobulin E (IgE) is increasingly recognized as a key component of asthma pathophysiology and contributes to both the early- and late-phase inflammatory cascade of the airways by inhibiting allergen-induced activation of mast cells. Both epidemiologic and clinical evidence support the use of IgE blockade for asthma treatment. Omalizumab is currently the only IgE-targeted therapy approved by the United States Food and Drug Administration for asthma treatment. The drug improves symptoms, reduces exacerbations, and improves quality of life in certain patient populations.
Asthma is a chronic inflammatory airway disease characterized by acute episodes of bronchoconstriction that are usually reversible. In the United States, asthma imposes a substantial burden, as approximately 20.5 million Americans (6.2 million persons < 18 yrs of age) reported having asthma in 2004. Despite advances in pharmacotherapy and asthma management, many patients with moderate-to-severe disease have persistent symptoms, which lead to physician visits, emergency department visits, hospitalizations, and missed work or school days. This situation results in lifestyle limitations and high expenses. In 2004, the total cost related to asthma was approximately $16 billion. The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) 3-year observational study showed that much of the asthma-related morbidity and utilization of health care resources affected patients with moderate-to-severe and/or difficult-to-treat asthma (Figure 1).
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Patient nonadherence and poor inhalation technique are common and most likely contribute to persistent symptoms. However, the prospective Gaining Optimal Asthma Control (GOAL) study showed that symptoms were uncontrolled in as many as 29% of patients with moderate-to-severe asthma despite aggressive pharmacotherapy, good adherence (virtually 100%), and tightly monitored inhalation techniques. In such individuals, a variety of comorbid diseases, such as gastroesophageal reflux disease, thyroid disease, vocal cord dysfunction, left ventricular dysfunction, and upper airway disease (e.g., seasonal allergies), may complicate symptoms of asthma. Triggers, such as respiratory infections (particularly viral infections), indoor allergens, and environmental exposures (e.g., to smoke), may also aggravate asthma symptoms.
Another notable contributor to persistent symptoms in patients with asthma is a genuine lack of response to pharmacotherapy. Patient characteristics (e.g., genetics, environmental influences) and drug properties (e.g., formulation, delivery system, molecular target) pose considerable and distinctive challenges to the management of asthma symptoms.
Patients with moderate-to-severe asthma often have persistent symptoms despite aggressive pharmacotherapy, enthusiastic patient compliance, and proper technique in using delivery devices. Persistent symptoms have detrimental effects on patients' quality of life and result in a tremendous financial burden because of an increased utilization of health care resources. Guidelines from the National Asthma Education and Prevention Program list symptom prevention, near-normal lung function, and participation in activities (e.g., school, work) as goals of successful asthma therapy. The development of pharmacologic and biologic therapies that target different aspects of airway inflammation will help patients with persistent asthma symptoms achieve these goals. Immunoglobulin E (IgE) is increasingly recognized as a key component of asthma pathophysiology and contributes to both the early- and late-phase inflammatory cascade of the airways by inhibiting allergen-induced activation of mast cells. Both epidemiologic and clinical evidence support the use of IgE blockade for asthma treatment. Omalizumab is currently the only IgE-targeted therapy approved by the United States Food and Drug Administration for asthma treatment. The drug improves symptoms, reduces exacerbations, and improves quality of life in certain patient populations.
Asthma is a chronic inflammatory airway disease characterized by acute episodes of bronchoconstriction that are usually reversible. In the United States, asthma imposes a substantial burden, as approximately 20.5 million Americans (6.2 million persons < 18 yrs of age) reported having asthma in 2004. Despite advances in pharmacotherapy and asthma management, many patients with moderate-to-severe disease have persistent symptoms, which lead to physician visits, emergency department visits, hospitalizations, and missed work or school days. This situation results in lifestyle limitations and high expenses. In 2004, the total cost related to asthma was approximately $16 billion. The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) 3-year observational study showed that much of the asthma-related morbidity and utilization of health care resources affected patients with moderate-to-severe and/or difficult-to-treat asthma (Figure 1).
(Enlarge Image)
Patient nonadherence and poor inhalation technique are common and most likely contribute to persistent symptoms. However, the prospective Gaining Optimal Asthma Control (GOAL) study showed that symptoms were uncontrolled in as many as 29% of patients with moderate-to-severe asthma despite aggressive pharmacotherapy, good adherence (virtually 100%), and tightly monitored inhalation techniques. In such individuals, a variety of comorbid diseases, such as gastroesophageal reflux disease, thyroid disease, vocal cord dysfunction, left ventricular dysfunction, and upper airway disease (e.g., seasonal allergies), may complicate symptoms of asthma. Triggers, such as respiratory infections (particularly viral infections), indoor allergens, and environmental exposures (e.g., to smoke), may also aggravate asthma symptoms.
Another notable contributor to persistent symptoms in patients with asthma is a genuine lack of response to pharmacotherapy. Patient characteristics (e.g., genetics, environmental influences) and drug properties (e.g., formulation, delivery system, molecular target) pose considerable and distinctive challenges to the management of asthma symptoms.