Effect of omalizumab on symptoms of seasonal allergic rhinitis: a randomized controlled trial.

CONTEXT: Seasonal allergic rhinitis is a common IgE-mediated disorder that produces troublesome symptoms. A recombinant humanized monoclonal anti-IgE antibody (omalizumab) forms complexes with free IgE, blocking its interaction with mast cells and basophils and lowering free IgE levels in the circulation. OBJECTIVE: To assess the efficacy and safety of omalizumab for prophylaxis of symptoms in patients with seasonal allergic rhinitis. DESIGN: Randomized, double-blind, dose-ranging, placebo-controlled trial conducted from July 25 through November 21, 1997. SETTING: Twenty-five outpatient centers throughout the United States. PATIENTS: Five hundred thirty-six patients aged 12 to 75 years with at least a 2-year history of moderate to severe ragweed-induced seasonal allergic rhinitis and a baseline IgE level between 30 and 700 IU/mL. INTERVENTIONS: Patients were randomly assigned to receive omalizumab, 50 mg (n = 137), 150 mg (n = 134), or 300 mg (n = 129), or placebo (n = 136) subcutaneously just prior to ragweed season and repeated during the pollen season every 3 weeks in patients with baseline IgE levels of 151 to 700 IU/mL (4 total treatments) and every 4 weeks in patients with baseline IgE levels of 30 to 150 IU/mL (3 total treatments). MAIN OUTCOME MEASURES: Self-assessed daily nasal symptom severity scores (range, 0-3), rescue antihistamine use, and rhinitis-specific quality of life during the 12 weeks from the start of treatment. RESULTS: Nasal symptom severity scores were significantly lower in patients who received 300 mg of omalizumab than in those who received placebo (least squares means, 0.75 vs 0.98, respectively; P =.002). A significant association was observed between IgE reduction and nasal symptoms and rescue antihistamine use. Rhinitis-specific quality of life scores were consistently better in patients who received 300 mg of omalizumab than in those who received lower dosages or placebo and did not decline during peak season. The frequency of adverse events was not significantly different among the omalizumab and placebo groups. CONCLUSION: Omalizumab decreased serum free IgE levels and provided clinical benefit in a dose-dependent fashion in patients with seasonal allergic rhinitis.

Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma.

BACKGROUND: 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. OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of omalizumab in the treatment of inhaled corticosteroid-dependent asthma. METHODS: 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. RESULTS: 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. CONCLUSION: The addition of omalizumab to standard asthma therapy reduces asthma exacerbations and decreases inhaled corticosteroid and rescue medication use.

Treatment of childhood asthma with anti-immunoglobulin E antibody (omalizumab).

BACKGROUND AND OBJECTIVE: There seems to be a strong causal relationship between allergy and the origins of asthma. Susceptibility to both is determined by a combination of genetics and environment acting through a complex network of cytokines. Nearly 90% of affected children have positive skin tests indicating the presence of specific immunoglobulin E (IgE), with sensitivity to house dust mite, Alternaria, cockroach, cat, and dog most closely linked to the disease. Greater exposure to house dust mite during infancy leads to earlier onset of wheezing, and elevated serum IgE levels correlate with the appearance of asthma symptoms. Specific IgE binds to high-affinity (FcepsilonRI) receptors on mast cells and basophils. The IgE-mediated reactions that follow exposure of sensitized mast cells to an allergen are designated early- and late-phase asthmatic responses (EAR and LAR). EAR is characterized by release of histamine and other preformed mediators within 1 hour of allergen exposure. It is often followed by LAR, an infiltration of the airways by inflammatory cells associated with an episode of more prolonged, and usually more severe airflow obstruction, 4 to 8 hours after antigen exposure. Chronic airway symptoms result from persistent LAR caused by continuous allergen exposure. IgE antibodies are capable of passive transfer of both EAR and LAR sensitivity. IgE-mediated mast cell activation contributes to chronic tissue eosinophilia and airway remodeling, with permanent loss in pulmonary function. Omalizumab (rhuMAb-E25) is a recombinant, humanized, monoclonal anti-IgE antibody of mouse origin developed for the treatment of IgE-mediated diseases. Omalizumab binds to free IgE at the same site as the high-affinity receptor. Although it attaches to free IgE, it does not bind to IgA, IgG, or cell-bound IgE. It therefore does not induce cross-linking of cell-bound IgE, which would lead to the release of allergic mediators. It has been reported to decrease serum IgE levels in a dose-dependent manner, inhibit EAR and LAR, and cause a down-regulation of FcepsilonRI receptors on basophils. Omalizumab has been reported to be safe and effective in improving asthma control and reducing the requirement for oral and inhaled corticosteroids. This double-blind, randomized, placebo-controlled study evaluated the safety, steroid-sparing effects, and impact on disease exacerbations of omalizumab in the treatment of childhood asthma. Methods. Participants were 334 males and premenarchal females aged 6 to 12 years, with moderate to severe allergic asthma requiring treatment with inhaled corticosteroids. During a run-in phase, all children were switched to equivalent doses of beclomethasone dipropionate (BDP), and the dose was adjusted to assure maintenance of asthma control achieved with previous corticosteroid treatment. Children were randomized to subcutaneously administered placebo (N = 109) or omalizumab (N = 225) at a dose based on body weight and initial serum IgE (0.016 mg/kg/IgE [IU/mL] per 4 weeks). BDP dose (initial range 168-420 microg/d) was kept stable for 16 weeks (stable-steroid phase), reduced over 8 weeks to the minimum effective dose (steroid-reduction phase), and maintained constant for the final 4 weeks. RESULTS: More participants in the omalizumab group decreased their BDP dose, and their reduction was greater than that of the placebo group (median reduction 100% vs 66.7%). BDP was withdrawn completely in 55% of the omalizumab group versus 39% of the placebo group. The incidence and the frequency of asthma exacerbations requiring treatment with doubling of BDP dose or systemic corticosteroids were lower in the omalizumab group. The treatment differences were statistically significant during the steroid-reduction phase, during which fewer participants in the omalizumab group had asthma exacerbation episodes (18.2% vs 38.5%), and the mean number of episodes per patient was smaller than with placebo (0.42 vs 2.72). Five asthma exacerbations requiring hospitalization all occurred in the placebo group. Participants' and investigators' global evaluations of treatment effectiveness were more favorable for omalizumab than placebo. Investigators rated effectiveness excellent for 31.5% of the omalizumab group versus 16.3% of the placebo group and good for 44.7% of the omalizumab group versus 32.7% of the placebo group. There was little change in asthma symptom scores or spirometry measurements during either the stable-steroid or steroid dose-reduction phase, with minimal differences between the treatment groups. The requirement for rescue medication in the omalizumab group during both the stable-steroid and steroid dose-reduction phases was consistently lower than at baseline. At week 28, the median number of puffs of rescue medication taken daily was 0 in the omalizumab group and 0.46 in the placebo group. The change from baseline was significant in favor of omalizumab. (ABSTRACT TRUNCATED)

Effect of an antiseptic mouthrinse on salivary microbiota.

PURPOSE: To evaluate the effect of rinsing with original formulation Listerine Antiseptic (LA) on the level of viable salivary bacteria for periods up to 1 hour. MATERIALS AND METHODS: In this double-blind, controlled, cross-over study, unstimulated saliva was collected from 25 subjects, serially diluted, and cultured on selective and non-selective media under aerobic and anaerobic conditions. Streptococci, Veillonella sp., and total aerobic and anaerobic flora were enumerated just prior to and 2, 15, 30, and 60 minutes after rinsing for 30 seconds with either 20 ml of LA or a 5% hydroalcohol control rinse. RESULTS: After the control rinse, total flora cultivated on MM10 agar exhibited a non-significant (P > 0.05) 10%-20% decrease relative to baseline. In contrast, rinsing with LA resulted in a significant (P < 0.05) 60%-65% decrease from baseline in all four microbial groups at 2 minutes; except in the case of Veillonella, the significant decreases were sustained up to 60 minutes. Total Listerine group aerobic, anaerobic and streptococcal counts were significantly lower than placebo (P < 0.05). The significant reduction in salivary bacterial levels seen in the Listerine group for up to 60 minutes suggests that this antiseptic mouthrinse may have use clinically as a pre-procedural rinse to decrease the level of viable microorganisms in aerosols generated during dental procedures.