Bruce G. Martin

Fluticasone propionate given once daily is as effective for seasonal allergic rhinitis as beclomethasone dipropionate given twice daily

Fluticasone propionate was compared with beclomethasone dipropionate for the treatment of allergic rhinitis in a multicenter, double-blind, randomized, placebo-controlled study during the mountain cedar (Juniperus ashei) pollination season in central Texas. Adults (n = 313) with moderate to severe symptoms were treated with fluticasone propionate aqueous nasal spray 200 micrograms once a day or beclomethasone dipropionate aqueous nasal spray 168 micrograms twice a day or placebo for 2 weeks. Fluticasone propionate administered once daily and beclomethasone dipropionate administered twice daily were equally effective as assessed by clinician- and patient-rated scores for nasal obstruction, rhinorrhea, sneezing, and nasal itching throughout the treatment and follow-up periods. Both regimens were more effective than placebo. Adverse events were related to topical administration and were similar in frequency and nature in all three treatment groups. Fluticasone propionate and beclomethasone dipropionate displayed a similar safety profile that did not differ from placebo. We conclude that fluticasone propionate aqueous nasal spray administered as 200 micrograms once daily in the morning is as safe and effective as beclomethasone dipropionate aqueous nasal spray administered as 168 micrograms twice daily for seasonal allergic rhinitis.

Comparison of fluticasone propionate aqueous nasal spray and oral montelukast for the treatment of seasonal allergic rhinitis symptoms.

BACKGROUND Few studies have directly compared the efficacy of intranasal corticosteroids with that of leukotriene receptor antagonists for the treatment of daytime and nighttime symptoms of seasonal allergic rhinitis (SAR). OBJECTIVE To compare fluticasone propionate aqueous nasal spray, 200 microg daily, with oral montelukast, 10 mg daily, for the relief of SAR symptoms. METHODS Patients with SAR 15 years or older were randomized to receive either fluticasone propionate (n = 367) or montelukast (n = 369) in this double-blind, double-dummy, parallel-group study. The primary efficacy measure was the mean change from baseline in daytime total nasal symptom scores (TNSSs) (the sum of 4 daytime individual nasal symptom scores [INSSs] assessing nasal congestion, itching, rhinorrhea, and sneezing), averaged across weeks 1 and 2. Secondary efficacy measures included the 4 daytime INSSs, nighttime TNSSs (the sum of 3 nighttime INSSs assessing congestion on awakening, difficulty going to sleep, and nighttime awakenings), and the 3 nighttime INSSs averaged across weeks 1 and 2. RESULTS Mean changes from baseline in daytime TNSSs (P < .001), all daytime INSSs (P < .001), nighttime TNSSs (P < .001), and all nighttime INSSs (P < or = .02) showed significant differences favoring fluticasone propionate over montelukast across 2 weeks of treatment. CONCLUSION Compared with montelukast, fluticasone propionate provided significantly greater improvement in daytime and nighttime SAR symptoms.

Effectiveness of fluticasone furoate 110 μg once daily in the treatment of nasal and ocular symptoms of seasonal allergic rhinitis in adults and adolescents sensitized to mountain cedar pollen

ABSTRACT Background: Fluticasone furoate (FF) is a novel enhanced-affinity corticosteroid for the treatment of allergic rhinitis, delivered by a unique side-actuated device. This study was designed to investigate the efficacy and safety of FF nasal spray (FFNS) 110 μg once daily compared with placebo in adults and adolescents (aged ≥12 years) with seasonal allergic rhinitis (SAR) symptoms caused by mountain cedar (Juniperus ashei) pollen. Methods: This was a randomized, double-blind, placebo-controlled, parallel-group, phase III study conducted over a 2-week period (between 10 December 2004 and 19 January 2005) at seven study sites, in Austin, Texas, USA, and San Antonio, Texas, two metropolitan cities in the central Texas Hill Country located approximately 80 miles apart. Adult and adolescent patients (aged ≥12 years) with SAR, who were sensitized to mountain cedar (Juniperus ashei) pollen, were randomized to receive either FFNS 110 μg (n = 152) or placebo (n = 150) once daily. Patients rated the severity of each nasal symptom (rhinorrhea, nasal congestion, nasal itching, and sneezing) and ocular symptom (redness, watery eyes, itching and burning) on a 4-point categorical scale (0 = none, 3 = severe) in a reflective and instantaneous manner. Patients also rated their overall evaluation of response to therapy. Results: FFNS significantly improved the nasal symptoms of SAR compared with placebo. The least square (LS) mean difference in the reflective total nasal symptom score (TNSS) was −0.777 (p = 0.003). A significant reduction in morning pre-dose instantaneous TNSS was also observed compared with placebo (LS mean difference −0.902; p < 0.001). Patients receiving FFNS had significantly greater improvements from baseline in reflective total ocular symptom scores (TOSS) than those receiving placebo (LS mean difference −0.546; p = 0.008). Significant improvements in ocular symptoms with FFNS versus placebo were also observed for morning pre-dose instantaneous TOSS (LS mean difference −0.519; p = 0.009). FFNS had a favorable safety and tolerability profile: fewer adverse events occurred with FFNS (22%) than with placebo (29%), and no serious adverse events were observed. Conclusions: FFNS 110 μg once daily demonstrated efficacy in relieving both the nasal and ocular symptoms of SAR in adult and adolescent patients. Trial registration: ClinicalTrials.gov identifier: NCT00115622.

Fluticasone furoate nasal spray is more effective than fexofenadine for nighttime symptoms of seasonal allergy.

Nasal symptoms of allergic rhinitis are an important cause of sleep disturbance. Reduction of nasal symptoms, particularly nasal obstruction, has been linked to improvements in self-reported sleep quality. The enhanced-affinity intranasal corticosteroid fluticasone furoate and the oral antihistamine fexofenadine were compared with respect to nighttime symptoms of seasonal allergic rhinitis. In two randomized, double-blind, double-dummy, parallel-group studies, patients received fluticasone furoate nasal spray (FFNS),110 microg (study 1, n = 312; study 2, n = 224); fexofenadine, 180 mg (study 1, n = 311; study 2, n = 227); or placebo (study 1, n = 313; study 2, n = 229) once daily for 2 weeks. Fluticasone furoate was more effective (p < 0.001) than fexofenadine and placebo in both studies with respect to the mean changes from baseline over the treatment period in the nighttime symptoms score, nighttime reflective total nasal symptom score, predose instantaneous nasal symptom score, and morning peak nasal inspiratory flow. Fluticasone furoate was more effective than placebo (p <or= 0.001) in study 1 and more effective than both placebo and fexofenadine (p <or= 0.034) in study 2 with respect to the mean changes from baseline in the nighttime reflective total ocular symptom score and predose instantaneous total ocular symptom score. In these double-dummy studies, fexofenadine did not separate from placebo in comparisons of the nighttime symptoms score or the nighttime nasal or ocular symptom measures. The incidence of adverse events was similar among groups. FFNS once daily was more effective than fexofenadine and placebo with respect to nighttime sleep disturbance caused by seasonal allergy symptoms.

Cross allergenicity among grasses determined by tissue threshold changes

Twenty-seven volunteers with grass-pollen allergy who had not received prior immunotherapy had titrated prick tests with fivefold dilutions of 10 grasses (timothy, Bermuda, smooth brome, grama, salt, quack, western wheat, Johnson, June, and Bahia) to a final dilution of 1:3,906,250 w/v. Ten subjects served as untreated control subjects. Seventeen subjects received immunotherapy with an extract containing equal parts of timothy and Bermuda. Twelve months later subjects had repeat titrated skin testing with reconstituted aliquots of the same lyophilized extract, at the same time of day, and at the same location on the back as in the initial testing period. Nine treated subjects and eight control subjects completed the study protocol. The skin test areas with all 10 grass extracts were significantly decreased in the treated group compared to the control group (p less than 0.01), and there was no difference in the extent of the reduction among the 10 grasses by analysis of variance. We conclude that immunotherapy to timothy and Bermuda alone is capable of reducing to a similar degree the clinical sensitivity to all 10 grasses studied. The results of this study suggest that treatment with timothy and Bermuda alone may be sufficient in most grass-sensitive individuals.

The Efficacy of Fluticasone Propionate Aqueous Nasal Spray for Allergic Rhinitis and Its Relationship to Topical Effects

Fluticasone propionate aqueous nasal spray is an intranasal corticosteroid for the treatment of patients with allergic rhinitis. This double-masked, double-dummy, parallel-group study was conducted to confirm that the efficacy of fluticasone propionate nasal spray is attributable to topical rather than systemic effects. A total of 304 patients with documented seasonal allergic rhinitis were randomly assigned to receive fluticasone propionate nasal spray 200 micrograms once daily (n = 77), oral fluticasone propionate 5 mg once daily (n = 73), oral fluticasone propionate 10 mg once daily (n = 77), or placebo (n = 77) for 14 days. Plasma fluticasone propionate concentrations were determined at baseline and after 14 days of treatment (day 15). Nasal symptoms were recorded daily by patients and assessed weekly by clinicians. On day 15, more patients in the oral fluticasone propionate 5-mg or 10-mg groups, compared with patients in the fluticasone propionate nasal spray group or the placebo group, had detectable plasma fluticasone propionate concentrations, and mean concentrations were higher in the oral fluticasone propionate groups. Both clinician- and patient-rated total and individual nasal symptom scores for obstruction, rhinorrhea, sneezing, and itching were significantly lower in the fluticasone propionate nasal spray group compared with either of the oral fluticasone propionate groups or the placebo group. With few exceptions, oral fluticasone propionate (5 mg or 10 mg) was not significantly different from placebo on any measures of efficacy. These findings indicate that the efficacy of fluticasone propionate nasal spray (200 micrograms once daily) in the treatment of allergic rhinitis results from direct topical effects rather than from indirect effects after systemic absorption.

A study of the efficacy and safety of ciclesonide hydrofluoroalkane nasal aerosol in patients with seasonal allergic rhinitis from mountain cedar pollen.

A nasal aerosol formulation of ciclesonide with a hydrofluoroalkane propellant (CIC-HFA) is currently in development for treatment of allergic rhinitis (AR). This study evaluated the efficacy and safety of once-daily administration of CIC-HFA 74 or 148 micrograms compared with placebo in patients with seasonal AR (SAR) from mountain cedar pollen. Patients ≥12 years of age with a ≥2-year history of SAR from mountain cedar pollen were randomized in a placebo-controlled, double-blind, parallel group, multicenter study to CIC-HFA 74 micrograms, CIC-HFA 148 micrograms, or placebo once daily in the morning for 2 weeks. Change from baseline in reflective total nasal symptom score (rTNSS), instantaneous TNSS (iTNSS), and reflective total ocular symptom score (rTOSS) in patients with baseline rTOSS ≥5.00 were evaluated. Adverse events (AEs) were monitored throughout the study. A statistically significant improvement in rTNSS (least squares [LS] mean change from baseline 1.04 and 1.02 respectively; p < 0.0001 versus placebo for both) and iTNSS (LS mean change from baseline 0.90 and 0.83 respectively; p < 0.001 vs placebo for both) was observed after treatment with CIC-HFA 74- or 148-microgram doses. Only the CIC-HFA 74-micrograms treatment group showed a statistically significant improvement in rTOSS (LS mean change from baseline 0.52; p = 0.0124) compared with placebo. The overall incidence of AEs was low and comparable between the treatment groups. In this study, statistically significant improvements in nasal symptoms of SAR were observed after treatment with CIC-HFA 74-microgram or CIC-HFA 148-microgram doses. Both active treatments were well tolerated. Clinical trial registry URL and registration number: www.clinicaltrials.gov/ct2/show/NCT01010971.

Efficacy and safety of levocabastine nasal spray for seasonal allergic rhinitis.

This multicenter, double-blind, placebo-controlled trial evaluated the efficacy and safety of levocabastine nasal spray, a potent and selective H1-receptor antagonist, in the control of histamine-mediated symptoms of seasonal allergic rhinitis. Adults with ≥2 year history of allergic rhinitis due to Mountain Cedar were randomized to treatment with levocabastine nasal spray (0.2 mg twice daily) or placebo for 28 days during the 1994–1995 Mountain Cedar allergy season. Patients assessed the severity of their rhinitis symptoms on a four-point scale twice daily. At the end of the trial, patients also performed a global evaluation of treatment efficacy on a five-point scale. Overall for the 4-week treatment period, levocabastine nasal spray significantly reduced major nasal (runny nose and sneezing) and primary rhinitis (runny nose, sneezing, and itchy/gritty eyes) symptoms compared with placebo on both repeated measures (p = 0.023; p = 0.01) and ANOVA (p = 0.003; p < 0.001) analyses. Global evaluations of treatment efficacy at the end of the trial significantly favored levocabastine over placebo (p = 0.002). Overall, the incidence of adverse events was similar for both treatment groups. In general, most adverse events were mild in intensity, with sinusitis (17% each group), headache (17% placebo, 14% levocabastine), and rhinitis (8% placebo, 2% levocabastine) most commonly reported. Levocabastine nasal spray 0.2 mg twice daily was significantly more effective than placebo in the relief of histamine-mediated symptoms in patients with seasonal allergic rhinitis and was well tolerated over the 28-day treatment period.