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      Therapeutics and Clinical Risk Management (submit here)

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      New approaches to managing asthma: a US perspective

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          Abstract

          Despite remarkable advances in diagnosis and long-term management, asthma remains a serious public health concern. Newly updated expert guidelines emphasize the intra- and inter-individual variability of asthma and highlight the importance of periodic assessment of asthma control. These guidelines update recommendations for step-wise asthma treatment, address the burgeoning field of asthma diagnostics, and stress the importance of a patient and health care professional partnership, including written action plans and self monitoring. The field of asthma therapeutics is expanding rapidly, with promising new treatment options available or in development that may address some of the existing barriers to successful asthma management. These approaches simplify treatment, use combinations of agents in one delivery device that have complementary actions, or target specific pathways involved in asthma patho-physiology. Considerable activity is taking place in asthma pharmacogenetics. This review provides an overview of these new approaches to managing asthma, including their present status and future potential.

          Most cited references129

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          Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE.

          Patients with severe persistent asthma who are inadequately controlled despite Global Initiative for Asthma (GINA) 2002 step 4 therapy are a challenging population with significant unmet medical need. We determined the effect of omalizumab on clinically significant asthma exacerbations (requiring systemic corticosteroids) in the first omalizumab study to exclusively enrol patients from this difficult-to-treat patient population. Following a run-in phase, patients (12-75 years) inadequately controlled despite therapy with high-dose inhaled corticosteroids (ICS) and long-acting beta(2)-agonists (LABA) with reduced lung function and a recent history of clinically significant exacerbations were randomized to receive omalizumab or placebo for 28 weeks in a double-blind, parallel-group, multicentre study. A total of 419 patients were included in the efficacy analyses. The clinically significant asthma exacerbation rate (primary efficacy variable), adjusted for an observed relevant imbalance in history of clinically significant asthma exacerbations, was 0.68 with omalizumab and 0.91 with placebo (26% reduction) during the 28-week treatment phase (P = 0.042). Without adjustment, a similar magnitude of effect was seen (19% reduction), but this did not reach statistical significance. Omalizumab significantly reduced severe asthma exacerbation rate (0.24 vs 0.48, P = 0.002) and emergency visit rate (0.24 vs 0.43, P = 0.038). Omalizumab significantly improved asthma-related quality of life, morning peak expiratory flow and asthma symptom scores. The incidence of adverse events was similar between treatment groups. In patients with inadequately controlled severe persistent asthma, despite high-dose ICS and LABA therapy, and often additional therapy, omalizumab significantly reduced the rate of clinically significant asthma exacerbations, severe exacerbations and emergency visits. Omalizumab is effective and should be considered as add-on therapy for patients with inadequately controlled severe persistent asthma who have a significant unmet need despite best available therapy.
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            Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma.

            A recombinant humanized anti-IgE mAb, omalizumab, forms complexes with free IgE, blocking its interaction with mast cells and basophils; as a consequence, it might be effective in the treatment of asthma. The purpose of this study was to evaluate the efficacy and safety of omalizumab in the treatment of inhaled corticosteroid-dependent asthma. In this phase III, double-blinded, placebo-controlled trial, 525 subjects with severe allergic asthma requiring daily inhaled corticosteroids were randomized to receive placebo or omalizumab subcutaneously every 2 or 4 weeks, depending on baseline IgE level and body weight. Inhaled corticosteroid doses were kept stable over the initial 16 weeks of treatment and tapered during a further 12-week treatment period. Omalizumab treatment resulted in significantly fewer asthma exacerbations per subject and in lower percentages of subjects experiencing an exacerbation than placebo treatment during the stable steroid phase (0.28 vs 0.54 [P =.006] and 14.6% vs 23.3% [P =.009], respectively) and during the steroid reduction phase (0.39 vs 0.66 [P =.003] and 21.3% vs 32.3% [P =.004], respectively). Beclomethasone dipropionate reduction was significantly greater with omalizumab treatment than with placebo (median 75% vs 50% [P <.001]), and beclomethasone dipropionate discontinuation was more likely with omalizumab (39.6% vs 19.1% [P <.001]). Improvements in asthma symptoms and pulmonary function occurred along with a reduction in rescue beta-agonist use. Omalizumab was well tolerated, with an adverse-events profile similar to that of placebo. The addition of omalizumab to standard asthma therapy reduces asthma exacerbations and decreases inhaled corticosteroid and rescue medication use.
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              Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma: 10-year follow-up on the PAT study.

              3-year subcutaneous specific immunotherapy (SIT) in children with seasonal allergic rhinoconjunctivitis reduced the risk of developing asthma during treatment and 2 years after discontinuation of SIT (5-year follow-up) indicating long-term preventive effect of SIT. We evaluated the long-term clinical effect and the preventive effect of developing asthma 7-years after termination of SIT. One hundred and forty-seven subjects, aged 16-25 years with grass and/or birch pollen allergy was investigated 10 years after initiation of a 3-year course of SIT with standardized allergen extracts of grass and/or birch or no SIT respectively. Conjunctival provocations were performed outside the season and methacholine bronchial provocations were performed during the season and winter. Asthma was assessed by clinical evaluation. The significant improvements in rhinoconjunctivitis and conjunctival sensitivity persisted at the 10-year follow-up. Significantly less actively treated subjects had developed asthma at 10-year follow-up as evaluated by clinical symptoms [odds ratio 2.5 (1.1-5.9)]. Patients who developed asthma among controls were 24/53 and in the SIT group 16/64. The longitudinal treatment effect when adjusted for bronchial hyper-responsiveness and asthma status at baseline including all observations at 3, 5 and 10 years follow-up (children with or without asthma at baseline, n = 189; 511 observations) was statistically significant (P = 0.0075). The odds ratio for no-asthma was 4.6 95% CI (1.5-13.7) in favor of SIT. A 3-year course of SIT with standardized allergen extracts has shown long-term clinical effects and the potential of preventing development of asthma in children with allergic rhinoconjunctivitis up to 7 years after treatment. Specific immunotherapy has long-term clinical effects and the potential of preventing development of asthma in children with allergic rhino conjunctivitis up to 7 years after treatment termination.
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                Author and article information

                Contributors
                Allergy and Asthma Associates of Southern California Mission Viejo, CA, USA
                Journal
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                April 2008
                April 2008
                : 4
                : 2
                : 363-379
                Affiliations
                Allergy and Asthma Associates of Southern California Mission Viejo, CA, USA
                Author notes
                Correspondence: William E Berger Allergy and Asthma Associates of Southern California, 27800 Medical Center Road, Suite 244, Mission Viejo, CA 92691-6410, USA Tel +1 949 364 2900 Fax +1 949 365 0117 Email weberger@ 123456uci.edu
                Article
                2504058
                18728834
                62fa6f33-0056-49b2-8010-d3ec10f205c1
                © 2008 Dove Medical Press Limited. All rights reserved
                History
                Categories
                Review

                Medicine
                guidelines,pharmacogenetics,long-acting β2-adrenergic agonists,inhaled corticosteroids,asthma treatment

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