Assessment of recent evidence for the management of patients with systemic sclerosis-associated interstitial lung disease: a systematic review.

This systematic review summarises current evidence to help guide treatment decisions for patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD). A systematic search of the literature (January 2012 to April 2018), including grey literature (searched between 1992 and 2011), was conducted using multiple electronic databases. Guidelines, meta-analyses, randomised controlled trials and observational studies reporting on risk stratification, screening, diagnosis, treatment and management outcomes for patients with SSc-ILD were included. A quality assessment of the included evidence was undertaken. In total, 2464 publications were identified and 280 included. Multiple independent risk factors for ILD in patients with SSc were identified, including older age, male sex and baseline pulmonary function. High-resolution computed tomography (HRCT) has been used for characterising ILD in patients with SSc, and pulmonary function tests are a key adjunctive component in the diagnostic and monitoring pathway. The clinical value of biomarkers relating to SSc-ILD diagnosis or assessment for disease progression is unknown at present. Immunosuppressive therapy (monotherapy or combined therapy) is the current standard of care for SSc-ILD; long-term evidence for effective and safe treatment of SSc-ILD is limited. Identification of patients at risk for SSc-ILD remains challenging. HRCT and pulmonary function tests are key to diagnosing and monitoring for disease progression. Although immunosuppressive therapy is considered current first-line treatment, it is partly associated with adverse effects and long-term follow-up evidence is limited. Novel therapies and biomarkers should be further explored in well-controlled clinical studies.

The identification and management of interstitial lung disease in systemic sclerosis: evidence-based European consensus statements.

BACKGROUND: Systemic sclerosis-associated interstitial lung disease (ILD) carries a high mortality risk; expert guidance is required to aid early recognition and treatment. We aimed to develop the first expert consensus and define an algorithm for the identification and management of the condition through application of well established methods. METHODS: Evidence-based consensus statements for systemic sclerosis-associated ILD management were established for six domains (ie, risk factors, screening, diagnosis and severity assessment, treatment initiation and options, disease progression, and treatment escalation) using a modified Delphi process based on a systematic literature analysis. A panel of 27 Europe-based pulmonologists, rheumatologists, and internists with expertise in systemic sclerosis-associated ILD participated in three rounds of online surveys, a face-to-face discussion, and a WebEx meeting, followed by two supplemental Delphi rounds, to establish consensus and define a management algorithm. Consensus was considered achieved if at least 80% of panellists indicated agreement or disagreement. FINDINGS: Between July 1, 2018, and Aug 27, 2019, consensus agreement was reached for 52 primary statements and six supplemental statements across six domains of management, and an algorithm was defined for clinical practice use. The agreed statements most important for clinical use included: all patients with systemic sclerosis should be screened for systemic sclerosis-associated ILD using high-resolution CT; high-resolution CT is the primary tool for diagnosing ILD in systemic sclerosis; pulmonary function tests support screening and diagnosis; systemic sclerosis-associated ILD severity should be measured with more than one indicator; it is appropriate to treat all severe cases; no pharmacological treatment is an option for some patients; follow-up assessments enable identification of disease progression; progression pace, alongside disease severity, drives decisions to escalate treatment. INTERPRETATION: Through a robust modified Delphi process developed by a diverse panel of experts, the first evidence-based consensus statements were established on guidance for the identification and medical management of systemic sclerosis-associated ILD. FUNDING: An unrestricted grant from Boehringer Ingelheim International.

No mucosal atrophy and reduced inflammatory cells: active-controlled trial with yearlong fluticasone furoate nasal spray.

BACKGROUND: Fluticasone furoate nasal spray (FFNS) and mometasone furoate nasal spray (MFNS) are well tolerated and more effective than placebo at relieving the symptoms of seasonal and perennial allergic rhinitis. Effects of FFNS on the nasal histology have not been previously reported. This study examines the effects of FFNS and MFNS, administered daily for 1 year, on the nasal mucosa in subjects with perennial allergic rhinitis. METHODS: Subjects with perennial allergic rhinitis were randomized 1:1 to q.d., open-label treatment with FFNS, 110 µg, or MFNS, 200 µg, for 1 year. These groups and a healthy control group that did not receive study medication underwent nasal biopsies at baseline and 12 months. RESULTS: The nasal biopsy population comprised 96 participants (37 using FFNS, 42 using MFNS, and 17 healthy controls). Epithelial thickness did not change appreciably from baseline to week 52 in any of the groups and mean change from baseline did not differ between FFNS and MFNS (least square mean difference, -0.001 mm, 95% confidence interval, -0.007, 0.006). Although not tested for significance, improvements over baseline were observed in epithelial histology in the FFNS group with more epithelium including intact columnar and ciliated epithelial cells. No appreciable change in the percentage of goblet cells was established. FFNS and MFNS were associated with decreases in epithelial and subepithelial nasal mucosal eosinophils and basophils from baseline to week 52. The percentage of subjects with no inflammatory cells at week 52 was 49 and 33% for eosinophils and 46 and 24% for basophils, for FFNS and MFNS, respectively. CONCLUSION: Yearlong therapy with either FFNS or MFNS showed no changes in epithelial thickness or the percentage of goblet cells as well as a reduction in inflammatory cell infiltrate. FFNS was associated with improvements in epithelial histology. These data support the long-term safety of FFNS in subjects with perennial allergic rhinitis.

An integrated analysis of the efficacy of fluticasone furoate nasal spray on individual nasal and ocular symptoms of seasonal allergic rhinitis.

Intranasal steroids have been shown to affect ocular symptoms of allergic rhinitis (AR). The results of the published literature, however, are not uniform across all products. This study was designed to evaluate whether the effects of fluticasone furoate nasal spray (FFNS) are consistent across different allergy seasons and different geographic regions for individual nasal and ocular symptoms of seasonal allergic rhinitis (SAR). An integrated analysis was performed on data from four randomized, double-blind, placebo-controlled, parallel-group, multicenter trials, designed to evaluate the efficacy and safety of FFNS, 110 micrograms, once daily for 14 days in 1141 adult and adolescent SAR patients exposed to mountain cedar, ragweed, or grass pollen allergen. All patients evaluated severity of seven individual nasal and ocular symptoms on a 4-point categorical scale. The main efficacy measures included change from baseline in daily reflective, morning (A.M.) predose instantaneous, and daily A.M. and evening (P.M.) reflective score for each nasal/ocular symptom. FFNS significantly improved daily mean reflective, A.M. predose instantaneous, and daily A.M. and P.M. reflective scores for nasal itching, sneezing, congestion, rhinorrhea, and ocular itching/burning, tearing/watering, and redness, compared with placebo (p < 0.001 for all versus placebo). The least square (LS) mean treatment differences ranged from -0.44 to -0.33 (p < 0.0001) for the individual nasal symptoms and from -0.22 to -0.19 (p < 0.0001) for the individual ocular symptoms. FFNS also significantly improved daily reflective total nasal symptom scores (TNSS)/reflective total ocular symptom scores (TOSS), and A.M. predose instantaneous TNSS and instantaneous TOSS, compared with placebo (LS mean treatment differences = -1.47, -0.65, -1.49, and -0.63, respectively; p < 0.001 for all). FFNS, 110 micrograms, once daily consistently relieved all nasal and ocular symptoms of SAR across different allergy seasons and geographical locations.

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

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.

Preferences of adult patients with allergic rhinitis for the sensory attributes of fluticasone furoate versus fluticasone propionate nasal sprays: a randomized, multicenter, double-blind, single-dose, crossover study.

BACKGROUND: Product attributes influence patient preference for intranasal corticosteroid therapy in allergic rhinitis (AR). OBJECTIVE: The aim of the study was to compare the product sensory attributes and patient preferences of fluticasone furoate (FF) and fluticasone propionate (FP) nasal sprays in patients with symptomatic perennial and/or seasonal AR. METHODS: This randomized, multicenter, double-blind, single-dose, crossover study enrolled 127 patients with a diagnosis of AR as determined by respiratory symptoms and a positive skin test to perennial and/or seasonal allergens within 12 months prior to the study. Patients could not use FF or FP within 4 weeks prior to the start of the study. Patients were randomized 1:1 to receive FF (110 microg) followed by FP (200 microg) or FP followed by FF. A 10-minute washout period occurred before crossover dosing. Following each treatment, patient-rated sensory attributes were assessed immediately and 2 minutes after treatment on 2 questionnaires using a 7-point Likert scale (scored from 0-6) rating odor, taste, aftertaste, drip down the throat, urge to sneeze, soothing feeling, irritation, and nose runoff. At the end of the crossover dosing and after completion of the attributes questionnaires, preference for individual attributes of FF or FP nasal spray and overall patient preference were evaluated in a third questionnaire that asked "Based on these attributes, which product did you prefer overall?" Additionally, a follow-up phone call was conducted 24 hours after the study to assess any adverse events following study treatment. RESULTS: Patients (mean age, 39.7 years; 80% white; 65% women) preferred FF nasal spray over FP nasal spray overall (60% vs 33%; P = 0.003) and based on the individual attributes of odor (64% vs 29%; P < 0.001), taste (47% vs 21%; P < 0.001), aftertaste (44% vs 22%; P = 0.002), drip down the throat (43% vs 27%; P = 0.037), and nose runoff (49% vs 19%; P < 0.001). Patient ratings favored FF versus FP (median differences, P < 0.001) with respect to odor, taste, dripping down the throat, and nose runoff, both immediately and 2 minutes after dosing, but there were no significant differences with respect to whether the medication felt soothing, caused nasal irritation, or made patients sneeze. Fifty-two percent (63/121) of patients replied that they were very likely to comply with FF treatment versus FP treatment (38% [45/120]; P = 0.02) if the medications were prescribed. Three patients (2%) reported adverse events (dizziness, headache, nasal congestion) during treatment with FF. CONCLUSION: In this study of adult AR patients, the sensory attributes of FF were preferred over those of FP following single-dose administration.

Optimal dose selection of fluticasone furoate nasal spray for the treatment of seasonal allergic rhinitis in adults and adolescents.

Efficacy and safety of fluticasone furoate nasal spray, administered using a unique side-actuated device, were evaluated in patients > or =12 years of age with seasonal allergic rhinitis to determine the optimal dose. A randomized, double-blind, parallel-group, placebo-controlled, dose-ranging study was performed on 641 patients who received placebo (n=128) or fluticasone furoate, 55 microg (n=127), 110 microg (n=127), 220 microg (n=129), or 440 microg (n=130), once daily for 2 weeks. Fluticasone furoate was significantly more effective than placebo for mean changes from baseline over the 2-week treatment period in daily reflective total nasal symptom score (primary end point; p < 0.001 each dose vs. placebo), morning predose instantaneous total nasal symptom score (p < 0.001 each dose versus placebo), daily reflective total ocular symptom score (p < or = 0.013 each dose versus placebo), and morning predose instantaneous total ocular symptom score (p < or = 0.019 for three highest doses versus placebo). The onset of action for fluticasone furoate nasal spray versus placebo was observed 8 hours after the first. dose of study medication in the 110 and 440 microg treatment groups (p < or = 0.032). The incidence of adverse events, results of clinical laboratory tests, and changes in 24-hour urinary cortisol values were similar between active treatment groups and placebo. The preliminary profile of fluticasone furoate is that of a rapidly effective therapy that confers 24-hour efficacy for both nasal and ocular symptoms with once-daily dosing. The 110-microg dose was chosen for phase III development because it achieved statistically significant and clinically meaningful results for all efficacy end points and provided the optimal risk-benefit ratio.

Fluticasone furoate nasal spray: a single treatment option for the symptoms of seasonal allergic rhinitis.

BACKGROUND: Fluticasone furoate (USAN-approved name) is a novel, enhanced-affinity glucocorticoid administered in a unique side-actuated device for the management of seasonal allergic rhinitis (SAR). OBJECTIVE: We sought to evaluate the efficacy and safety of once-daily fluticasone furoate nasal spray, 110 microg, in patients aged 12 years or older with fall SAR. METHODS: Patients (n = 299) received fluticasone furoate or placebo for 2 weeks in this double-blind, parallel-group randomized study. Patients evaluated nasal and ocular symptoms using a 4-point categoric scale. Efficacy was assessed on the basis of the mean change from baseline in reflective and instantaneous total nasal symptom scores and reflective total ocular symptom scores. RESULTS: Fluticasone furoate produced significantly greater improvements than placebo in daily reflective total nasal symptom score (-1.473, P < .001; primary end point), morning predose instantaneous total nasal symptom score (-1.375, P < .001), daily reflective total ocular symptom score (-0.600, P = .004), and patient-rated overall response to therapy (P < .001). The onset of therapeutic effect occurred at 8 hours after initial administration. Fluticasone furoate was well tolerated. CONCLUSION: Fluticasone furoate, 110 microg once daily, was effective and well tolerated for the treatment of nasal symptoms of SAR in patients aged 12 years and older. Treatment also produced significant improvements in ocular symptoms. Fluticasone furoate was fast acting, as indicated by an 8-hour onset of action, and provided 24-hour symptom control. CLINICAL IMPLICATIONS: New treatments for the bothersome symptoms of SAR are needed. One such treatment, fluticasone furoate nasal spray, provides effective relief of the symptom profile of SAR.

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.

Concurrent use of intranasal and orally inhaled fluticasone propionate does not affect hypothalamic-pituitary-adrenal-axis function.

Two double-blind, randomized, placebo-controlled, parallel group safety and efficacy studies included evaluation of the hypothalamic-pituitary-adrenal (HPA)-axis effects of concurrent treatment with intranasal and orally inhaled fluticasone propionate (FP). In the first study, patients with asthma who were > or =12 years of age were assigned randomly to receive twice-daily doses (either 88 or 220 microg) of orally inhaled FP delivered from a metered-dose inhaler (MDI). In the second study, patients were assigned randomly to receive either orally inhaled FP 250 microg or orally inhaled FP 250 microg/salmeterol 50 microg delivered via the Diskus device. In both studies, patients with rhinitis were allowed to continue the use of intranasal FP at their usual dosing. Treatment periods were 26 weeks and 12 weeks for the MDI and Diskus studies, respectively. HPA-axis effects were assessed using response to short cosyntropin stimulation testing. The number and percentage of patients with an abnormal cortisol response, defined as a morning plasma cortisol of <5 microg/dL, a poststimulation peak of <18 microg/dL, or a poststimulation rise of <7 microg/dL, were summarized in two subgroups: patients who used intranasal FP and those who did not. The concurrent administration of intranasal FP and orally inhaled FP via an MDI or Diskus or via Diskus with salmeterol was not associated with HPA-axis effects compared with orally inhaled FP alone. The results of these two studies suggest that concurrent use of intranasal FP with orally inhaled FP administered via MDI or Diskus for treatment of comorbid rhinitis and asthma does not increase the risk of HPA-axis abnormalities.

Obstructive sleep apnea, nasal congestion, and snoring: their systemic effects and impact on quality of life.

A literature review was conducted to evaluate the available published data on sleep-related breathing disorders with a focus on obstructive sleep apnea (OSA) syndrome, nasal congestion, and snoring. The MEDLINE database was used to obtain pertinent reviews and articles. The pathophysiology of snoring, a partial blockage of the airway, and of apnea or total airway obstruction, is described. Contributing factors to the etiology of the OSA syndrome as well as current methods of diagnosis are discussed. Adverse systemic sequelae of the OSA syndrome, especially those pertaining to the cardiovascular and respiratory systems, are detailed. Treatment options, both nonsurgical and surgical, which are used to improve the quality of life of patients with these disorders, are presented also.

The efficacy of intranasal fluticasone propionate in the relief of ocular symptoms associated with seasonal allergic rhinitis.

Intranasal corticosteroids have been shown to decrease ocular symptoms associated with allergic rhinitis as well as nasal symptoms. The primary objective of this retrospective analysis was to evaluate the efficacy of fluticasone propionate (FP) aqueous nasal spray in the treatment of ocular symptoms in patients with seasonal allergic rhinitis (SAR). We pooled efficacy data from seven multicenter, randomized, double-blind, placebo-controlled studies of similar design. Each study evaluated the efficacy of intranasal FP, 200 micrograms, given once daily in the treatment of nasal and ocular symptoms associated with SAR. At baseline and after 7 and 14 days of treatment, clinicians rated the severity of four individual ocular symptoms (itching, tearing, redness, and puffiness) via visual analog scales of 0-100, where 0 = no symptoms and 100 = worst symptoms. The four ratings were added to form the total ocular symptom score (TOSS). Patients rated the overall severity of their ocular symptoms (all symptoms evaluated with a single score) daily on diary cards in a similar fashion. The primary outcome was the mean change from baseline in the clinician-rated TOSS. A between-group difference of 25 points in the mean change from baseline TOSS by day 14 was considered clinically relevant. The FP group had greater mean changes from baseline in the TOSS and in all four individual symptom scores compared with placebo at days 7 and 14. At day 7, mean decreases from baseline in the TOSS were 76.0 points for the FP group and 50.9 points for the placebo group (p < 0.001), a difference between groups of 25.1. At day 14, mean decreases from baseline in the TOSS were 91.8 points for the FP group and 60.2 points for the placebo group (p < 0.001), a difference between groups of 31.6. Consistent with the clinician-rated data, patient-rated data showed a significantly greater reduction in the overall ocular symptom score for the FP group compared with placebo for both weeks 1 and 2 (p < 0.001). Intranasal FP provides safe and effective relief of ocular symptoms associated with SAR. Patients with allergic rhinitis who also have ocular symptoms as a component of their disease may benefit from intranasal FP monotherapy without the addition of topical ophthalmologic agents or oral antihistamines. Such an approach may have advantages regarding compliance and cost-effectiveness of treatment.

Fluticasone propionate aqueous nasal spray improves nasal symptoms of seasonal allergic rhinitis when used as needed (prn).

BACKGROUND: Few published clinical trials document the efficacy of intranasal corticosteroids used as needed for treatment of seasonal allergic rhinitis. OBJECTIVE: To evaluate the efficacy and safety of 4 weeks' treatment with fluticasone propionate aqueous nasal spray 200 microg used as needed (FP200PRN) in patients with seasonal allergic rhinitis. METHODS: A randomized, double-blind, placebo-controlled study in 241 patients (> or = 12 years of age) with a positive skin test result to a relevant fall allergen and who were symptomatic at randomization. The primary endpoint was the mean change from baseline in total nasal symptom score (TNSS; the sum of nasal congestion, rhinorrhea, sneezing, and nasal itching, each rated on a 4-point scale from 0 = none to 3 = severe). RESULTS: The mean percentage of days that patients used the study medications in the FP200PRN and placebo groups was 61.8% (SD = 30.4%) and 70.1% (SD = 28.3%), respectively. Patients treated with FP200PRN had a significantly greater reduction from baseline in TNSS compared with those treated with vehicle placebo (mean +/- SE = -2.02 +/- 0.18 vs -1.06 +/- 0.22, P < 0.001), representing a 91% greater improvement with FP200PRN than vehicle placebo. The FP200PRN group also had a significantly greater (P < 0.001) mean reduction in individual nasal symptoms of rhinorrhea, sneezing, nasal itching, and nasal congestion compared with placebo. FP200PRN was well tolerated, with an incidence of adverse events comparable to vehicle placebo. CONCLUSIONS: FP200PRN in patients 12 years and older is effective for treatment of nasal symptoms associated with seasonal allergic rhinitis. It has a lower incidence of adverse events than typically associated with regular once-daily use.

Lack of effect of fluticasone propionate aqueous nasal spray on the hypothalamic-pituitary-adrenal axis in 2- and 3-year-old patients.

OBJECTIVE: Fluticasone propionate aqueous nasal spray (FP) at the highest recommended doses does not affect hypothalamic-pituitary-adrenal (HPA) axis function in adults or older children, but its potential effects in children younger than 4 years have not been previously studied. This randomized, double-blind, placebo-controlled study evaluated the effects of FP on HPA axis function measured by 12-hour urinary-free cortisol levels in children 2 to 3 years of age. METHODS: Patients ages 2 to 3 years with symptoms of allergic rhinitis were administered FP 200 microg/day (FP200 QD) or vehicle placebo for 6 weeks. RESULTS: The FP200 QD group (n = 33) was equivalent to the placebo group (n = 32) in mean change from baseline in the primary safety measure of 12-hour creatinine-corrected urinary-free cortisol concentration (geometric mean difference [standard error; SE] for placebo-FP200 QD = 0.96 [1.20]; 95% confidence interval 0.66, 1.39) at the end of the treatment period. The adjusted geometric mean change from baseline value was 0.98 for FP200 QD (SE = 1.14) and 0.94 for placebo (SE = 1.15); a value of 1.0 reflects no change from baseline. Cough and fever were the most common adverse events reported in either group. CONCLUSIONS: FP200 QD was equivalent to placebo with respect to effects on HPA axis function measured by 12-hour urinary-free cortisol in 2- and 3-year-old patients. FP200 QD was well-tolerated in these very young children with allergic rhinitis.

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.

Relief of sinus pain and pressure with fluticasone propionate aqueous nasal spray: a placebo-controlled trial in patients with allergic rhinitis.

Although allergic rhinitis is commonly associated most with symptoms of nasal congestion, rhinorrhea, sneezing, and itching, the symptom of sinus pain and pressure often prompts the patient to seek medical attention. The effect of fluticasone propionate on this symptom has not been studied. The purpose of this study was to compare the efficacy and safety of fluticasone propionate aqueous nasal spray to placebo vehicle in the treatment of patients with sinus pain and pressure arising from allergic rhinitis. A multicenter, double-blind, parallel-group trial was conducted in 206 symptomatic patients > or = 12 years with seasonal or perennial allergic rhinitis. Patients were treated for 14 days with either fluticasone propionate aqueous nasal spray, 200 mcg once daily, or placebo vehicle. Patients attended clinic visits and kept diary cards rating sinus pain and pressure (measured as one symptom) and nasal congestion symptoms during the study. Treatment with fluticasone propionate provided significantly greater relief of symptoms of sinus pain and pressure compared with placebo over the entire 14-day treatment period. Nasal congestion scores also were significantly reduced compared with placebo at each time point. Treatments were well tolerated, and the incidence of adverse events attributable to study treatments was similar between groups. Our data indicate that symptoms of sinus pain and pressure and nasal congestion can be significantly reduced in patients with allergic rhinitis when treated with fluticasone propionate aqueous nasal spray, 200 mcg once daily.

No growth suppression in children treated with the maximum recommended dose of fluticasone propionate aqueous nasal spray for one year.

This randomized, double-blind, placebo-controlled study of fluticasone propionate aqueous nasal spray (at a maximum recommended dose of 200 micrograms each day) administered daily for one year was conducted to evaluate its potential effects on growth, measured by stadiometry, in prepubescent children with perennial allergic rhinitis (n = 150; age 3.5 to 9.0 years). The results demonstrate equivalent growth velocity over a one-year treatment period between children receiving fluticasone propionate aqueous nasal spray and children receiving vehicle placebo. In addition, children in both treatment groups had similar increases in height over the same period. Baseline height was 119.1 cm (SE = 0.72) in the fluticasone propionate group (n = 56) and 119.0 cm (SE = 0.71) in the vehicle placebo group (n = 52). Mean height at the end of one year of treatment was 125.5 cm (SE = 0.18) in the fluticasone propionate group (n = 44) and 125.4 cm (SE = 0.19) in the vehicle placebo group (n = 39) (least-squares mean difference -0.12; 95% confidence interval [-0.600, 0.352]). The effects of fluticasone propionate on one-year growth velocity were also comparable to those of vehicle placebo. The confidence interval for the treatment difference lay within the prospectively defined equivalence bounds (of -0.8, +0.8 cm/year) and contained zero. The incidence of adverse events considered to be at least possibly drug-related did not differ between the fluticasone propionate group and the vehicle placebo group. The results of this one-year, double-blind study demonstrate that fluticasone propionate aqueous nasal spray at the maximum recommended dose of two sprays per nostril (200 micrograms) once daily was equivalent to vehicle placebo with no effects on growth rate in prepubescent children.