Edward E. Philpot

Fluticasone Propionate Nasal Spray Is Superior to Montelukast for Allergic Rhinitis While Neither Affects Overall Asthma Control

BACKGROUND Asthma and allergic rhinitis are both highly prevalent diseases and often coexist in patients. OBJECTIVE To investigate the effect of rhinitis therapy on asthma outcomes in adult and adolescent patients with both seasonal allergic rhinitis (SAR) and persistent asthma. METHODS A total of 863 patients (mean baseline FEV1 81% predicted) were randomized to receive open-label fluticasone propionate/salmeterol (FSC), 100/50 microg bid for 4 weeks, plus either blinded fluticasone propionate aqueous nasal spray (FPANS) 200 microg/d, montelukast 10 mg/d, or placebo. Patients kept daily records of peak expiratory flow (PEF), asthma, and rhinitis symptoms and rescue albuterol use. RESULTS FPANS added to FSC resulted in superior outcomes for daytime total nasal symptom scores (D-TNSS) and individual daytime nasal specific symptoms (congestion, rhinorrhea, sneezing, and itching) compared with montelukast plus FSC and placebo plus FSC (p < or = 0.001). Montelukast plus FSC was superior to placebo plus FSC only for D-TNSS and itching and sneezing. Morning PEF, asthma symptoms, and rescue albuterol use improved significantly (p < or = 0.001) in all treatment groups, but improvements were comparable across the treatment groups. CONCLUSION In patients with persistent asthma treated with FSC, the addition of montelukast or FPANS for the treatment of SAR resulted in no additional improvements in overall asthma control compared with FSC alone. However, FPANS provided superior rhinitis control compared with montelukast. These data suggest that asthma and rhinitis should each be optimally treated.

Treatment with intranasal fluticasone propionate significantly improves ocular symptoms in patients with seasonal allergic rhinitis.

Background If monotherapy with an intranasal corticosteroid can alleviate both nasal and ocular symptoms of allergic rhinitis, treatment may be simplified and costs may be reduced.

Fluticasone propionate aqueous nasal spray provided significantly greater improvement in daytime and nighttime nasal symptoms of seasonal allergic rhinitis compared with montelukast

BACKGROUND The safety and efficacy of intranasal corticosteroids for the treatment of allergic rhinitis is well documented in the literature. Additionally, an expert panel has concluded that intranasal corticosteroids are the first line of therapy when obstruction is a major component of rhinitis. Montelukast is a leukotriene receptor antagonist recently approved for the treatment of seasonal allergic rhinitis (SAR). OBJECTIVE This randomized, double-blind, double-dummy, parallel-group study was conducted to compare the effectiveness of a 15-day course of intranasal fluticasone propionate 200 microg, once daily (FP200QD), to oral montelukast 10 mg, once daily (MON10QD), in relieving daytime and nighttime nasal symptoms associated with SAR. METHODS The intent-to-treat (ITT) analysis population consisted of 705 eligible males and females (> or = 15 years) with SAR randomized to either FP200QD (N = 353) or MON10QD (N = 352). The primary efficacy endpoint was the mean change from baseline in subject-rated daytime total nasal symptom scores (the sum of four individual scores: nasal congestion, itching, rhinorrhea, and sneezing), evaluated via visual analog scales, and averaged over weeks 1 to 2. Secondary endpoints included the four daytime individual nasal symptom scores, the nighttime total, and individual nasal symptom scores (each evaluated on a four-point scale from 0 to 3). RESULTS Statistically significant differences favoring FP200QD over MON10QD were observed for the mean change from baseline in daytime total nasal symptom scores (P < 0.001), daytime individual nasal symptom scores (P < 0.001), nighttime total (P < 0.001), and all individual nasal symptom scores (P < or = 0.002) over the 15-day treatment period. FP200QD and MON10QD were both well tolerated. CONCLUSIONS The results of this well controlled study demonstrated that FP200QD was consistently superior to MON10QD with regard to every efficacy endpoint evaluated, including daytime and nighttime nasal congestion, in subjects with SAR.

Safety of second generation antihistamines.

The sedation related to first-generation antihistamine use has been shown to compromise performance at school and at work, impair driving, and decrease the ability to handle tasks that require a high degree of alertness or concentration. Second-generation antihistamines are less likely to produce sedation. Loratadine, cetirizine, and fexofenadine are the most commonly prescribed second-generation antihistamines. Many tests have been conducted to assess the central effects of these three drugs. Compared with placebo, at recommended doses loratadine is not associated with performance impairment. Cetirizine, at recommended doses, has been shown to impair performance and cognition in several studies, although to a much lesser degree than older antihistamines. Clinical trials show fexofenadine is nonsedating, even at very high doses; psychomotor and driving tests reinforce these findings. Loratadine, cetrizine, and fexofenadine all have excellent safety records. Their cardiovascular safety has been demonstrated in drug-interaction studies, elevated-dose studies, and clinical trials. These three antihistamines have also been shown safe in special populations, including pediatric and elderly patients.

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.

Weather/temperature-sensitive vasomotor rhinitis may be refractory to intranasal corticosteroid treatment

Vasomotor rhinitis (VMR) is a common but poorly understood disorder of which there are two major subgroups: VMR(w/t), triggered by weather/temperature and VMR(ir), triggered by airborne irritants. No specific biological pathways or specific treatments for VMR(w/t) or VMR(ir) have been identified. However, intranasal corticosteroids (INSs) are effective in treating many forms of nonallergic rhinitis that include these conditions. A recently introduced INS with established efficacy in allergic rhinitis and enhanced affinity, fluticasone furoate, may possess the potency and safety profile required to treat chronic VMR(w/t). Two replicate studies (FFR30006 and FFR30007) were conducted in six countries to evaluate the efficacy and safety of fluticasone furoate nasal spray in subjects with VMR(w/t). After a 7- to 14-day screening period, subjects (n = 699) with symptomatic VMR(w/t) received fluticasone furoate, 110 mug q.d. or placebo for 4 weeks in these two randomized, double-blind, parallel-group studies. Subjects rated their nasal symptoms (congestion, rhinorrhea, and postnasal drip) twice daily on a 4-point categorical scale and evaluated their overall response to treatment at study end. Fluticasone furoate did not significantly improve daily reflective total nasal symptom scores, the primary end point, versus placebo (p = 0.259) and there was no improvement in any other measure of efficacy. The active treatment was well tolerated. Fluticasone furoate was not effective in treating subjects with a newly defined condition, weather-sensitive VMR. These unexpected results suggest that VMR(w/t) is a distinct subgroup of VMR that is refractory to treatment with INSs. Additional study of other treatments for VMR(w/t) (including INSs) is warranted.

Safety and efficacy of fluticasone furoate in pediatric patients with perennial allergic rhinitis

Objective To evaluate the safety and efficacy of once-daily (QD) fluticasone furoate (FF) nasal spray in children with perennial allergic rhinitis (PAR). Study Design A global, randomized, double-blind, placebo-controlled study. Subjects and Methods Pediatric patients (aged 2–11 years; n = 558) with PAR received once-daily placebo, FF 110 μg, or FF 55 μg for 12 weeks. Efficacy was evaluated by nasal symptom scores. General safety and corticosteroid-specific safety (nasal and ophthalmic examinations, and hypothalamic—pituitary—adrenal assessments) were assessed. Results No findings of clinical concern were identified from the safety assessments. For primary efficacy analysis of mean change from baseline over the first 4 weeks of treatment in daily reflective total nasal symptom score, FF 55 μg demonstrated significant improvement (P = 0.003) compared with placebo; however, the improvement for FF 110 μg versus placebo did not reach statistical significance (P = 0.073). Conclusion FF QD was well tolerated and demonstrated efficacy in children aged 2 to 11 years with PAR.

Effect of once-daily fluticasone furoate nasal spray on nasal symptoms in adults and adolescents with perennial allergic rhinitis

BACKGROUND Intranasal corticosteroids are recommended as first-line therapy for the treatment of allergic rhinitis. Fluticasone furoate is a novel enhanced-affinity glucocorticoid for the treatment of allergic rhinitis. OBJECTIVE To compare the efficacy and safety of intranasal fluticasone furoate with those of vehicle placebo nasal spray in adult and adolescent patients with perennial allergic rhinitis (PAR). METHODS After screening (7-14 days), patients 12 years and older with confirmed PAR were randomized to receive fluticasone furoate, 110 microg once daily, or placebo once daily intranasally for 4 weeks in this double-blind, multicenter study. The primary end point was mean change from baseline during the entire treatment period in daily reflective total nasal symptom score (rTNSS), recorded on diary cards by patients, using a 4-point categorical scale. RESULTS The mean reduction from baseline during the treatment period in daily rTNSS was significantly greater in fluticasone furoate recipients than in placebo recipients (P = .005). This finding was supported by significantly greater mean reductions in morning rTNSS and evening rTNSS (P = .004 and P = .011, respectively). A significantly greater mean reduction in instantaneous morning predose TNSS with fluticasone furoate compared with placebo (P = .006) confirmed the efficacy of once-daily administration. Fluticasone furoate was also significantly more effective than placebo in overall response to therapy (P = .005). CONCLUSIONS Fluticasone furoate nasal spray, 110 microg once daily, effectively relieved nasal symptoms of PAR in adults and adolescents 12 years and older.

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.

Efficacy and safety of once-daily fluticasone furoate nasal spray in children with seasonal allergic rhinitis treated for 2 wk

The objective of this study was to evaluate the efficacy and safety of fluticasone furoate (FF) nasal spray 55 and 110 μg once daily in children with seasonal allergic rhinitis (SAR). Patients (n = 554) received placebo nasal spray or FF, administered using a unique side‐actuated device, in a 2‐wk, randomized, double‐blind study. Symptoms were evaluated by patients using a 4‐point categorical scale. Efficacy assessments included reflective and instantaneous total nasal symptom scores (r/iTNSS). Primary analyses were conducted in patients aged 6–11 yr in the intent‐to‐treat population (ITT); the 2–11 yr group provided supportive analyses. In patients aged 6–11 yr, FF 110 μg once daily significantly improved the daily rTNSS compared with placebo. FF 55 μg once daily was only numerically better for rTNSS and iTNSS. Secondary pre‐dose iTNSS and overall response to therapy were significant with FF 110 μg. The significant findings for FF 110 μg were supported by analyses in the entire ITT population of 2–11 yr olds. Both doses of FF were well tolerated. These study results suggest that FF nasal spray administered once daily for 2 wk is well tolerated and effective for the treatment of SAR symptoms in children aged 2–11 yr.