ABSTRACT
UNLABELLED: This is an integrated analysis of data from patients with cystic fibrosis (CF) aged 6-21 years who were treated with up to seven cycles of tobramycin powder for inhalation (TIP(TM) ) over a period of at least 1 year. Safety and key efficacy endpoints were analyzed. RESULTS: The improvement in lung function and decrease in sputum P. aeruginosa (Pa) density from baseline were sustained over the 1-year treatment period. The number of adverse events (AEs) was low and did not increase with additional cycles of TIP treatment. Some increase in tobramycin minimum inhibitory concentration (MIC) was observed, but there was no significant increase in emergence of resistant strains based on the parenteral breakpoint for tobramycin. CONCLUSION: Efficacy of TIP was maintained for up to seven cycles. Long-term treatment with TIP was generally safe and well tolerated with no increase in AEs.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Cystic Fibrosis/complications , Pseudomonas Infections/drug therapy , Pseudomonas aeruginosa/drug effects , Sputum/drug effects , Tobramycin/therapeutic use , Administration, Inhalation , Adolescent , Child , Cystic Fibrosis/microbiology , Cystic Fibrosis/physiopathology , Double-Blind Method , Female , Humans , Male , Microbial Sensitivity Tests , Powders , Pseudomonas Infections/etiology , Sputum/microbiology , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Approximately 45% of patients with chronic urticaria have an IgG autoantibody directed to the alpha-subunit of the high-affinity IgE receptor (chronic autoimmune urticaria, CAU) leading to cutaneous mast cell and basophil activation. Treatment of allergic asthma with omalizumab produces rapid reduction in free IgE levels and subsequent decrease in Fc epsilon RI expression on mast cells and basophils. If this occurs in CAU, cross-linking of IgE receptors by autoantibody would be less likely, reducing cell activation and urticaria/angioedema. OBJECTIVE: To investigate the efficacy of omalizumab in patients with CAU symptomatic despite antihistamine therapy. METHODS: Twelve patients with CAU, identified by basophil histamine release assay and autologous skin test, with persistent symptoms for at least 6 weeks despite antihistamines, were treated with placebo for 4 weeks followed by omalizumab (>or=0.016 mg/kg/IU mL(-1) IgE per month) every 2 or 4 weeks for 16 weeks. Primary efficacy variable was change from baseline to the final 4 weeks of omalizumab treatment in mean Urticaria Activity Score (UAS, 0-9 scale). Changes in rescue medication use and quality of life were assessed. RESULTS: Mean UAS declined significantly from baseline to the final 4 weeks of omalizumab treatment (7.50 +/- 1.78 to 2.66 +/- 3.31, -4.84 +/- 2.86, P = .0002). Seven patients achieved complete symptom resolution. In 4 patients, mean UAS decreased, but urticaria persisted. One patient did not respond. Rescue medication use was reduced significantly, and quality of life improved. No adverse effects were reported or observed. CONCLUSION: This exploratory proof of concept study suggests omalizumab is an effective therapy for CAU resistant to antihistamines.
Subject(s)
Anti-Allergic Agents/therapeutic use , Antibodies, Monoclonal/therapeutic use , Autoimmune Diseases/drug therapy , Basophils/immunology , Mast Cells/immunology , Urticaria/drug therapy , Adult , Antibodies, Anti-Idiotypic , Antibodies, Monoclonal, Humanized , Autoantibodies/immunology , Autoantibodies/metabolism , Autoimmune Diseases/immunology , Basophils/metabolism , Female , Histamine H1 Antagonists/therapeutic use , Histamine Release/drug effects , Humans , Hydroxyzine/therapeutic use , Immunoglobulin E/blood , Male , Mast Cells/metabolism , Middle Aged , Omalizumab , Receptors, IgE/immunology , Receptors, IgE/metabolism , Urticaria/immunologyABSTRACT
Asthma in older adults is under-recognized and possibly associated with allergic triggers. We conducted a pooled analysis of omalizumab double-blind, placebo-controlled trials to evaluate efficacy in older adults. Data for the total study population and subjects aged > or = 50 years with moderate-severe allergic asthma were examined. We used Poisson regression to analyze the number of asthma exacerbations and logistic regression to evaluate treatment effectiveness. Symptom scores and total rescue medication puffs were evaluated by analysis of covariance. Omalizumab reduced the risk of clinically significant asthma exacerbations, led to a significantly greater response in patient/investigator-reported global effectiveness, improved asthma symptom scores, and reduced rescue medication use in adults > or = 50 years with moderate-severe allergic asthma.
