Despite the existence of internationally recognized, evidence-based guidelines for the management of asthma, the disease remains inadequately controlled in a significant number of patients. Several factors may play a role in this phenomenon, including access to care, comorbid conditions, and suboptimal adherence. Additional possibilities are that ideal treat ment regimens have not been fully elucidated and national standards have yet to be updated to reflect knowledge of recently approved treatment modalities. As newly discovered agents target different points in the asthma cascade, it is crucial to determine their appropriate place in treatment regimens.
At the completion of the phase 3 trials for omalizumab, its developers (Genentech/Novartis) and the Department of Health Policy at Jefferson Medical College convened a panel of asthma experts to revisit the NAEPP Guidelines of 1997 and to review the potential role of IgE blocker therapy within the current asthma guidelines. The panel consisted of leaders in the fields of allergy and immunology, pulmonology, pediatrics, and pharmacology, as well as medical executives representing major managed care organizations (MCOs). The panel endorsed the 1997 NAEPP recommendations for mild-intermittent and mild-persistent asthma but recommended several additions to the remainder of the guidelines in light of the new technology (Table 1).
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First, the panel addressed the problem of inadequate control of asthma in a high proportion of “persistent-asthma” categories and acknowledged the likely contribution of patient nonadherence to this lack of control in certain cases. The panel also recommended that guidelines include an aggressive and comprehensive education and evaluation program for patients who fall into the moderate-persistent and severe-persistent asthma categories, especially patients who are not able to achieve optimal control of their asthma. This program would include instruction on the use of devices, environmental control and avoidance measures, rescue action plans, and self-management and adherence techniques.
A second recommendation related to the actual treatment guidelines for patients with moderate-persistent and severe-persistent asthma. The panel agreed that distinguishing between these two states is difficult in clinical practice and questioned the value of making such a clinical distinction between these two suboptimally controlled groups. Further, differences in the treatment regimens associated with each were thought to be unnecessarily confusing, possibly contributing to lapses in patient adherence. Because of these concerns, the panel recommended eliminating the distinction between these categories, allowing for standardization of therapy among patients with suboptimally controlled asthma.
Finally, the panel encouraged a wider range of strategies for asthma management to supplement the current asthma guideline recommendations. The panel noted, on the basis of clinical trial data for omalizumab, that IgE-blocking therapy presents an attractive alternative for suboptimally controlled asthma after unsuccessful attempts with the established therapies. IgE-blocking therapy appears to reduce asthma exacerbation rates in patients who:
- are at least 12 years old.
- have evidence of reversible airway disease.
- have an IgE level of 30 IU/ml or more with an upper limit of 700 IU/ml in adults.
(Note: Attempts at therapy in patients with higher levels may be unsuccessful because of the inability to sufficiently reduce free IgE to the levels required for reducing Fee receptor I expression. A few clinicians have reported positive results in patients with borderline total IgE levels of less than 30 IU/ml.)
The panel recommended that IgE blockers be used as an alternative treatment in patients with inadequately controlled asthma who are using high-dose inhaled corticosteroids or who require frequent courses of systemic corticosteroids. The panel suggested that IgE blockers could also be considered in patients whose disease is inadequately controlled despite a three-month trial of medium-dose inhaled corticosteroids and long-acting beta agonists or leukotriene receptor agonists. The panel’s recommended additions to the current asthma guidelines are listed in Table 1. canadian pharmacy cialis
|Disease State||Daily Medication||Considerations for Anti-IgE Therapy|
|Severe-persistent asthma||Preferred Treatment:• High-dose inhaled corticosteroids
• Long-acting inhaled beta2 agonists
and (if needed)
• Corticosteroid tablets or syrup long term (2 mg/kg per day, generally not exceeding 60 mg/kg per day). Repeated attempts to reduce systemic corticosteroids and maintain control with high-dose inhaled corticosteroids.
|• Patient at least 12 years of age• Historical evidence of reversible disease (such as a 12% improvement in FEV with at least a 200-ml increase or a20% improvement in PEF)
• IgE level > 30 IU/mL
• Historical evidence of specific allergic sensitivity (i.e., positive skin test or blood test for specific IgE)
|Moderate-persistent asthma||Preferred Treatment:• Low- to medium-dose inhaled corticosteroids and long-acting beta2-agonists
Alternative Treatment (listed alphabetically):
• Increase inhaled corticosteroids within medium-dose range
• Low- to medium-dose inhaled corticosteroids and either a leukotriene modifier or theophylline (e.g., Generic Theolair)
|• Inadequately controlled* despite medium dose of inhaled corticosteroids for at least 3 months in combination with a trial of long-acting inhaled beta2-agonists or leukotriene modifiers (or medication intolerance)• Systemic corticosteroids or high-dose inhaled corticosteroids required to maintain adequate control
• May consider as directly observable therapy in patients not adhering to prescribed therapy
|Patient evaluation and education||All patients with persistent asthma require further evaluations and education, including identification of allergic triggers and comorbidities,and detailed advice regarding management of the condition.Types of Education:
Disease state Pharmacotherapy Environmental controls Immunotherapy Inhaler technique Action plan
|Mild-persistent asthma||Preferred Treatment:• Low-dose inhaled corticosteroids
Alternative Treatment (listed alphabetically):
• Cromolyn sodium (e.g., Intal Inhaler), leuko-triene modifiers,nedocromil (e.g.,Tilade)
• Sustained-release theophylline (e.g.,Theolair SR) to serum concentration of 5-15 mcg/ml
|Mild-intermittent asthma||No daily medication needed. Severe exacerbations may occur, separated by long periods of normal lung function and no symptoms;a course of systemic corticosteroids recommended.||None|
|* Examples of inadequate control: utilization of emergency department, hospitalization, or urgent-care visits; excessive use of short-acting beta2-agonist or use of oral steroids; and impairment in activities of daily living, such as work, school, exercise, and sleep. FEV = forced expiratory volume; IgE = immunoglobulin E; PEF = peak expiratory flow.|
Approximately six months following the FDA’s approval of omalizumab, in January 2004, a second consensus panel was convened to evaluate the first six months of real-world experience with the drug, to revisit the panel’s previous recommendations regarding clinical practice guidelines, and to address unanswered questions related to managing allergic asthma and the remaining barriers to acceptance as well as to implementing updates to the guidelines.
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The panel endorsed the previously released asthma guideline recommendations (i.e., the inclusion of criteria for consideration of IgE-blocker therapy and a comprehensive education and evaluation program). The panel also acknowledged several barriers to the appropriate dissemination of the updated asthma guidelines. These challenges included the problems of patient adherence as well as confusion related to the unclear definitions of “optimal control” and “allergic asthma.”
Unanswered questions specific to IgE blocker therapy included the duration and characteristics of the optimal drug trial with an IgE blocker, the definitions of the appropriate end-points of therapy, and the most appropriate mechanisms of payment for the drug.
Panel members also voiced general concerns about the difficulty of distributing new medical information and guidelines into the community of clinical practitioners.