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.

Fluticasone furoate nasal spray is effective and well tolerated for perennial allergic rhinitis in adolescents and adults.

BACKGROUND: Fluticasone furoate nasal spray (FFNS), an intranasal corticosteroid, has been shown to be effective in perennial allergic rhinitis in randomized, double-blind, placebo-controlled studies but has been less extensively studied in perennial allergic rhinitis than seasonal allergic rhinitis. This study was designed to evaluate the efficacy and safety of FFNS in perennial allergic rhinitis in adolescents and adults ≥12 years of age. METHODS: In this randomized, double-blind, placebo-controlled, parallel-group study (FFU111439), patients ≥12 years old with perennial allergic rhinitis received FFNS, 110 micrograms (n = 160), or placebo (n = 155) q.d. for 4 weeks. RESULTS: Over the entire treatment period, FFNS was significantly (p < 0.05) more effective than placebo with respect to mean changes from baseline in daily reflective total nasal symptoms (primary end point), morning and evening reflective total nasal symptoms, daily reflective individual nasal symptoms, morning predose instantaneous total and individual nasal symptoms, and morning and evening peak nasal inspiratory flow. FFNS did not show a statistically significant difference from placebo in comparisons of ocular symptom measures. Clinically meaningful improvement versus placebo was observed on the Rhinoconjunctivitis Quality of Life Questionnaire with Standardised Activities overall score. Adverse events reported in >3% of patients in a treatment group and reported more frequently with FFNS than placebo were epistaxis (15% FFNS, 8% placebo) and nasopharyngitis (5% FFNS, 1% placebo). CONCLUSION: Once-daily FFNS was well tolerated and more effective than placebo at improving nasal symptoms of perennial allergic rhinitis in adolescents and adults ≥12 years of age.

Comparison of patient preference for sensory attributes of fluticasone furoate or fluticasone propionate in adults with seasonal allergic rhinitis: a randomized, placebo-controlled, double-blind study.

BACKGROUND: Intranasal corticosteroids are first-line treatment for moderate-to-severe seasonal allergic rhinitis (AR). OBJECTIVES: To compare preferences for fluticasone furoate and fluticasone propionate nasal sprays after 1 week of treatment in patients with symptomatic seasonal AR. METHODS: Patients with seasonal AR were enrolled (n = 360) and randomized 1:1 to active treatment (fluticasone furoate, 110 microg, or fluticasone propionate, 200 microg, followed by crossover treatment for 1 week each) or matched placebo sequence with a 1-week washout before crossover dosing. Fluticasone furoate and fluticasone propionate efficacy was measured by change from baseline during 1 week in daily reflective total nasal symptom score (rTNSS) that assessed severity of rhinorrhea, nasal congestion, nasal itching, and sneezing. Patient preference for fluticasone furoate or fluticasone propionate was assessed at the end of the study by questionnaire. RESULTS: Three hundred sixty patients from 29 clinical sites in the Unites States were randomized and treated between August 1, 2007 and November 30, 2007. Most patients were white (73%) and female (59%), with a mean age of 38.3 years, and had had seasonal AR for at least 10 years (74%). Fluticasone furoate and fluticasone propionate each reduced the daily rTNSS compared with their respective placebos (least squares mean [SD] difference, -0.8 [0.24], P < .001, and -0.6 [0.24], P = .01, respectively). More patients (P < .001) preferred fluticasone furoate to fluticasone propionate based on attributes of scent or odor (58% vs 27%), aftertaste (60% vs 18%), leaking out of the nose and down the throat (59% vs 21%), and mist gentleness (57% vs 26%). No statistically significant differences were seen in preferences regarding ease of use, delivery method, or device comfort. CONCLUSION: Both fluticasone furoate and fluticasone propionate significantly improved symptoms in adult patients with seasonal AR. Most patients preferred the sensory attributes of fluticasone furoate to those of fluticasone propionate after 1 week of treatment.

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.

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

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 microg once daily compared with placebo in adults and adolescents (aged > or =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 > or =12 years) with SAR, who were sensitized to mountain cedar (Juniperus ashei) pollen, were randomized to receive either FFNS 110 microg (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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00115622. 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 microg once daily demonstrated efficacy in relieving both the nasal and ocular symptoms of SAR in adult and adolescent patients.

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.

HPA axis safety of fluticasone furoate nasal spray once daily in children with perennial allergic rhinitis.

The effects of intranasal corticosteroids (INSs) on the hypothalamic-pituitary-adrenal (HPA) axis should be assessed for any to be marketed INS. The objective of this study was to assess the effects of fluticasone furoate nasal spray (FFNS) on cortisol production (as a measure of HPA axis function) following 6 wk of treatment with FFNS 110 microg once daily (QD) compared with placebo in pediatric patients with perennial allergic rhinitis (PAR). In this double-blind, parallel-group study, patients (n = 112) aged 2-11 yr with a 1-yr history of PAR (6 months for patients aged 2-3 yr) were randomized in a 1:1 ratio to either placebo or FFNS. Serum cortisol (SC) concentrations and urinary cortisol (UC) excretion were measured over a 24-h period at the randomization (baseline) and final treatment (week 6) visits for HPA axis evaluation in a domiciled environment (overnight in the clinic). Plasma samples were collected for FFNS at several time points over the 24 h after the final dose for pharmacokinetic analyses. FFNS was non-inferior to placebo with respect to change from baseline (expressed as a ratio) in 24-h SC weighted mean. The lower limit of the two-sided 95% confidence interval (CI) for the treatment ratio was greater than the pre-specified non-inferiority margin of 0.8 (treatment ratio = 0.97, 95% CI 0.88-1.07). UC excretion over 24 h at baseline and end of treatment was similar between treatment groups; no patients had 24-h excretion levels below normal range after 6 wk of treatment. Plasma concentrations of FFNS were generally non-quantifiable (<10 pg/ml). Results of the current study indicate that FFNS 110 microg QD has no significant effect on HPA axis function in 2- to 11-yr-old pediatric patients with PAR.

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 microg 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 microg once daily significantly improved the daily rTNSS compared with placebo. FF 55 microg once daily was only numerically better for rTNSS and iTNSS. Secondary pre-dose iTNSS and overall response to therapy were significant with FF 110 microg. The significant findings for FF 110 microg 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.

Lack of effect on adult and adolescent hypothalamic-pituitary-adrenal axis function with use of fluticasone furoate nasal spray.

BACKGROUND: Intranasal corticosteroids are recommended as first-line therapy for allergic rhinitis (AR), and because of their pharmacologic class, hypothalamic-pituitary-adrenal (HPA) axis function is evaluated. OBJECTIVE: To evaluate whether cortisol production was suppressed (as a measure of HPA axis function) by 6 weeks of treatment with fluticasone furoate nasal spray, 110 microg once daily, in patients with perennial AR. METHODS: A double-blind, randomized, placebo- and active-controlled (prednisone), parallel-group study. Outpatients aged 12 to 65 years with perennial AR for 2 years or more were from 1 center in the United States and 1 center in Canada. Pharmacodynamic and pharmacokinetic samples were collected during 24-hour domiciled visits (overnight in clinic). Measurements included change from baseline in 24-hour serum cortisol weighted mean and 24-hour urinary free cortisol excretion, total 24-hour urinary free cortisol excretion and 6-beta hydroxycortisol excretion, and plasma concentration of fluticasone furoate. RESULTS: A total of 112 of 183 patients were randomized. Fluticasone furoate was noninferior to placebo with respect to the ratio from baseline in serum cortisol weighted mean (treatment ratio, 0.98; 95% confidence interval, 0.89 to 1.07). In contrast, use of prednisone, 10 mg once daily, significantly reduced the ratio from baseline compared with placebo. Change from baseline in 24-hour urinary cortisol excretion was similar in the fluticasone furoate and placebo groups. Plasma levels of fluticasone furoate were undetectable after 6 weeks of treatment. CONCLUSION: Fluticasone furoate nasal spray, 110 microg once daily, was not associated with HPA axis suppression in patients 12 years and older with perennial AR.

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.

Fluticasone furoate nasal spray: effective monotherapy for symptoms of perennial allergic rhinitis in adults/adolescents.

Intranasal corticosteroids are widely prescribed for the treatment of perennial allergic rhinitis (PAR). The purpose of this study was to evaluate the efficacy and tolerability of intranasal fluticasone furoate, a novel enhanced-affinity glucocorticoid, in patients > or =12 years of age with PAR in a global, randomized, double-blind, placebo-controlled, 6-week study. Patients (n = 302) received fluticasone furoate nasal spray (FFNS) 110 microg or vehicle placebo once daily (q.d.). The primary efficacy measure was mean change from baseline over the 6-week treatment period in daily reflective total nasal symptom score (TNSS). Secondary end points included mean change from baseline in total and individual reflective nasal and ocular symptom scores and in daily peak nasal inspiratory flow (PNIF). FFNS was significantly more effective than placebo in reducing daily reflective TNSS over the treatment period (least square [LS] mean difference, -1.256; p < 0.001). Significant improvements were also established in total ocular symptom score (LS mean difference, -0.506; p = 0.004 versus placebo) and in all individual nasal (p < 0.001) and ocular (p < 0.03) symptoms assessed in a reflective manner. Improvements in daily PNIF were significantly greater with FFNS than placebo (LS mean difference, 8.376 L/minute; p = 0.004). FFNS was well tolerated. In this study, FFNS 110 microg q.d. was well tolerated and effective in reducing the nasal and ocular symptoms of PAR in adult and adolescent patients > or =12 years of age.

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.

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 microg, or FF 55 microg 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 microg demonstrated significant improvement (P = 0.003) compared with placebo; however, the improvement for FF 110 microg 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.

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.