Reflective Total Nasal Symptom Score Research Articles

SEASONAL ALLERGIC RHINITIS NASAL SYMPTOM AND QUALITY OF LIFE IMPROVEMENTS WITH OLOPATADINE/MOMETASONE COMBINATION NASAL SPRAY

Introduction Seasonal allergic rhinitis (SAR) symptoms often impair quality of life (QoL). In two randomized, double-blind phase 3 studies, twice-daily GSP301 nasal spray, a fixed-dose combination of olopatadine hydrochloride/mometasone furoate, significantly improved reflective and instantaneous Total Nasal Symptom Scores (rTNSS, primary endpoint; iTNSS, secondary endpoint) vs placebo (presented elsewhere). Results of additional endpoints comparing the efficacy and QoL of GSP301 vs placebo are reported here. Methods In study 1 (NCT02631551; N=1,180) and study 2 (NCT02870205; N=1,176), patients with SAR (≥12 years) were randomized 1:1:1:1 to GSP301 (olopatadine 665μg/mometasone 25μg BID), olopatadine (665μg BID), mometasone (25μg BID), or placebo for 14 days. Mean changes from baseline in Physician-assessed Nasal Symptom Score (PNSS) and Rhinoconjunctivitis Quality of Life Questionnaire–Standardized Activities [RQLQ(S)] for GSP301 vs placebo were analyzed using mixed-effect model repeated measures (P Results GSP301 significantly improved PNSS vs placebo in study 1 (least squares mean difference [95% CI]: -0.82 [-1.26, -0.38], PPPPP Conclusions In two phase 3 SAR studies, twice-daily GSP301 treatment provided significant improvements in nasal symptoms and QoL vs placebo and was well tolerated.

LONG-TERM SAFETY AND EFFICACY OF OLOPATADINE/MOMETASONE COMBINATION NASAL SPRAY IN PATIENTS WITH PERENNIAL ALLERGIC RHINITIS

Introduction The efficacy and safety of GSP301 nasal spray, a newly developed investigational fixed-dose combination of olopatadine hydrochloride/mometasone furoate, was demonstrated in large 2-week seasonal allergic rhinitis studies. This study compared the 52-week safety (primary endpoint) and efficacy (secondary endpoint) of GSP301 in patients with perennial allergic rhinitis (PAR). Methods In this randomized, double-blind, parallel-group study (NCT02709538), 601 patients with PAR (≥12 years) were randomized 4:1:1 to twice-daily GSP301 (olopatadine 665μg/mometasone 25μg) and two GSP301 vehicle formulations (placebo pH 3.7 or 7.0). Treatment-emergent adverse events (TEAEs) were analyzed using descriptive statistics. Mean change from baseline in average 24-hour AM reflective and instantaneous Total Nasal Symptom Scores (rTNSS, iTNSS) for GSP301 vs placebo pH 3.7 were analyzed using mixed-effect model repeated measures (P Results At week 52, TEAEs occurred in 51.7%, 41.4%, and 53.5% of patients in the GSP301, placebo pH 3.7 and 7.0 groups. The most frequently reported TEAEs included upper respiratory tract infection, epistaxis, and headache. No clinically meaningful differences were observed in TEAE incidences or other safety assessments across treatments. At weeks 6 and 30, GSP301 significantly improved rTNSS and iTNSS vs placebo pH 3.7 (PPP=0.001) vs placebo pH 3.7, with significant improvements in individual symptoms (P Conclusions In this long-term study, GSP301 was well tolerated and provided significant and clinically meaningful improvements in PAR symptoms vs placebo.

Efficacy Analysis of MP-AzeFlu Compared with Fluticasone Propionate Nasal Spray in Children 6 through 11 Years of Age with Allergic Rhinitis

MP-AzeFlu (Dymista®) is a novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP) for treatment of allergic rhinitis. The objective of the current analysis was to evaluate the efficacy of MP-AzeFlu compared to FP administered 1 spray per nostril twice daily in children 6 through 11 years of age. This was a randomized, open-label, 3-month safety study in patients 4 through 11 years of age. Qualified patients had a history of AR, were in good health, and had no evidence of nasal mucosal erosion, nasal ulceration, nasal septum perforation, or any significant nasal disease. Randomization was in a 3:1 ratio (MP-AzeFlu [n=304]:FP [n=101]). Efficacy was not a pre-specified study objective but was evaluated by self-assessment of overall allergy symptom severity in a subset of patients 6 through 11 years (MP-AzeFlu [n=264]:[FP: n=89]). Symptom severity was scored on a 4-point scale from 0 to 3 (0 = none; 1 = mild; 2 = moderate; 3 = severe). Total symptom score at baseline was 1.73 in the MP-AzeFlu group and 1.80 in the FP group (max score: 3). Over the entire study period, patients treated with MP-AzeFlu experienced a -0.68 pt reduction in overall symptom score (corresponding to a -5.44 change from baseline in AM + PM reflective total nasal symptom score (rTNSS; max = 24), significantly greater relief than that afforded by FP (-0.54 pt reduction; Diff: -0.14; 95% CI: -0.28, -0.01; p=0.04). MP-AzeFlu provided significantly greater relief of AR symptoms than FP in children 6 through 11 years of age.

Therapeutic comparability of Dezrinit and Nazonex® in control of symptoms of allergic rhinitis. The results of a multicenter, open, randomized, comparative study in parallel groups

Background. To study efficacy and safety of Dezrinit (mometasone furoate, metered dose nasal spray, 200 pg/day) in comparison with Nasonex® (mometasone furoate, metered dose nasal spray, 200 pg/day) upon administration for 14 days in adult patients with seasonal allergic rhinitis. Materials and methods. A total of 141 patients were enrolled into the study at 8 study centers in the RF, of which 134 patients were randomized: 67 patients into the experimental group (Dezrinit) and 67 patients into the comparison group (Nasonex®). patients were randomized to receive treatment either with Dezrinit or Nasonex®. Efficacy was assessed based on reflective Total Nasal Symptom Score (rTNSS) and instantaneous Total Nasal Symptom Score (iTNSS); reflective Total Ocular Symptom Score (rTOSS) and instantaneous Total Ocular Symptom Score (iTOSS). Overall proportion of patients who responded to treatment was evaluated according to overall assessment of treatment efficacy both by a patient and by an investigator. AEs were reported for safety assessment. Results. After 14 days of treatment a marked improvement of symptoms was observed in both groups based on all assessed scores. Mean change (SD) in rTNSS from baseline was -11,91 (4,625) scores and -11,64 (4,58) scores in the experimental and comparison groups, respectively (within group differences, p

Efficacy of MP-AzeFlu in children with seasonal allergic rhinitis: Importance of paediatric symptom assessment.

This study aimed to assess the efficacy of MP-AzeFlu (a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate in a single spray) in children with seasonal allergic rhinitis (SAR) and explore the importance of child symptom severity assessment in paediatric allergic rhinitis (AR) trials. A total of 348 children (4-11 years) with moderate/severe SAR were randomized into a double-blind, placebo-controlled, 14-day, parallel-group trial. Efficacy was assessed by changes from baseline in reflective total nasal symptom score (rTNSS), reflective total ocular symptom score (rTOSS) and individual symptom scores over 14 days (children 6-11 years; n = 304), recorded by either children or caregivers. To determine whether a by-proxy effect existed, efficacy outcomes were assessed according to degree of child/caregiver rating. Moreover, total Paediatric Rhinitis Quality of Life Questionnaire (PRQLQ) score was compared between the groups. A statistically superior, clinically relevant efficacy signal of MP-AzeFlu versus placebo was apparent for PRQLQ overall score (diff: -0.29, 95% CI -0.55, -0.03; p = 0.027), but not for rTNSS (diff: -0.80; 95% CI: -1.75; 0.15; p = 0.099). However, as the extent of children's self-rating increased, so too did the treatment difference between MP-AzeFlu and placebo; MP-AzeFlu provided significantly better relief than placebo for rTNSS (p = 0.002), rTOSS (p = 0.009) and each individual nasal and ocular symptom assessed (except rhinorrhoea; p = 0.064) when children mostly rated their own symptoms. MP-AzeFlu is an effective treatment for AR in childhood. Caregivers are less able than children to accurately assess response to treatment with available tools. A simple paediatric-specific tool to assess efficacy in AR trials in children is needed.

IMPLICATION OF ALTERNATIVE MINIMAL CLINICALLY IMPORTANT DIFFERENCE THRESHOLD ESTIMATION METHODS ON TECHNOLOGY ASSESSMENT.

Various minimal clinically important difference (MCID) threshold estimation techniques have been applied to seasonal allergic rhinitis (SAR). The objectives of this study are to (i) assess the difference in magnitude of alternative SAR MCID threshold estimates and (ii) evaluate the impact of alternative MCID estimates on health technology assessment (HTA). Data describing change from baseline of the reflective Total Nasal Symptom Score (rTNSS) for four intranasal SAR treatments were obtained from United States Food and Drug Administration-approved prescribing information. Treatment effects were then compared with anchor-based MCID thresholds derived by Barnes et al. and thresholds obtained from an Agency for Healthcare Research and Quality (AHRQ) panel. The change in rTNSS score from baseline, represented as the average of the twice-daily recorded scores of the rTNSS, was -2.1 (p < .001) for azelastine hydrochloride 0.10%, 1.35 (p = .014) for ciclesonide, and -1.47 (p < .001) for fluticasone furoate. The change in the rTNSS score from baseline, represented by sum of the AM and PM score, was -2.7 for MP-AzeFlu (p < .001). The rTNSS change from baseline for each product was compared with anchor-based MCID threshold and the AHRQ panel estimates. Comparison of the observed treatment effect to the anchor-based and AHRQ panel MCID thresholds results in different conclusions, with clinically important differences being inferred when anchor-based estimates serve as the reference point. The AHRQ panel MCID threshold for the rTNSS was twelve times larger than the anchor-based estimates resulting in conflicting recommendations on whether different SAR treatments provide clinically meaningful benefit.

A new AR therapy (MP29‐02*): all of ARIA in one puff

Allergic rhinitis (AR) is increasing in prevalence and becoming more difficult to treat. There is a subset of patients who are refractory to ARIA-defined rhinitis management approaches [1]. Even though new treatments have been made available for symptomatic relief, no new class of medication was forthcoming, until recently. The situation has now changed. MP29-02* is a novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP) in an advanced delivery system. It benefits from antihistamine, mast-cell stabilizing, anti-leukotriene and anti-inflammatory properties, made up in a unique formulation and delivered using an improved device (vs marketed intranasal steroid sprays (INS)). MP29-02*’s novel formulation and spray characteristics (e.g. finer droplet size, consistent spray release, wider spray angle) were developed to improve drug deposition on the nasal mucosa and ensure optimal retention. The impact has been observed both pharmacokinetically, [2] and clinically [3,4]. MP2902* was created to be more effective than any existing symptomatic treatment for AR, have a rapid onset of action and a sustained effect. Delivered as a single spray from one device, the aim was to improve compliance, maximize convenience for patients and simplify dosing. This product provides more effective relief than currently considered gold standard treatment, INS. A recent publication by Meltzer et al, 4 re-assessed the efficacy of MP29-02* versus AZE and FP in an innovative and clinically relevant way by responder analyses. The authors determined different response cut-offs from 30 to 90% reflective total nasal symptom score (rTNSS) reduction from baseline. More MP29-02* patients achieved each response (vs FP or AZE), and days earlier. A response ceiling of ≥60% was identified above which INS failed to differentiate from placebo. This may explain why moderate/severe AR patients still complain of bothersome symptoms despite ARIA-guided treatment. Patients who remain symptomatic on monotherapy should experience a significant reduction in their symptoms with MP29-02*, exceeding that which they have experienced in the past, and many days faster than an INS. MP29-02* comprises all the pharmacological principles foreseen in the ARIA treatment algorithm. *Dymista

Efficacy and safety of beclomethasone dipropionate nasal aerosol in children with perennial allergic rhinitis

BackgroundBeclomethasone dipropionate (BDP) nasal aerosol (non-aqueous) is approved for management of seasonal and perennial allergic rhinitis (PAR) in adolescents and adults. ObjectiveTo evaluate the efficacy and safety of BDP nasal aerosol at 80 μg/day in children with PAR. MethodsThis 12-week, phase 3, double-blinded, placebo-controlled, parallel-group study randomized 547 children (4–11 years old) with PAR to once-daily BDP nasal aerosol at 80 μg/day or placebo. The primary end point was change from baseline in average morning and evening reflective total nasal symptom score (rTNSS) during the first 6 weeks of treatment in patients 6 to 11 years old. Changes from baseline in average morning and evening instantaneous TNSS (iTNSS) in children 6 to 11 years old and average rTNSS and iTNSS in children 4 to 11 years old were assessed during the first 6 weeks of treatment. ResultsImprovements were significantly greater with BDP nasal aerosol than with placebo during the first 6 weeks of treatment in children 6 to 11 years old in average morning and evening rTNSS and iTNSS (mean treatment difference −0.66 [P = .002] and −0.58 [P = .004], respectively). Improvements in average morning and evening rTNSS and iTNSS also were significantly greater in patients 4 to 11 years receiving BDP nasal aerosol than with placebo during the first 6 weeks of treatment (P = .002 and P = .004, respectively). Similar improvements were seen during 12 weeks of treatment. The safety profile of BDP nasal aerosol was comparable to that of placebo. ConclusionThe BDP nasal aerosol at 80 μg/day in children 4 to 11 years old was well tolerated and effective in controlling nasal symptoms of PAR. Trial Registrationwww.clinicaltrials.gov, identifier NCT01783548.

Comparison of intranasal ciclesonide, oral levocetirizine, and combination treatment for allergic rhinitis.

PurposeTo evaluate the efficacy and safety of once-daily ciclesonide in comparison to both levocetirizine alone, and a ciclesonide/levocetirizine combination in patients with seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR).MethodsSubjects exhibiting moderate to severe allergic rhinitis for longer than 1 year were randomized in an open-label, 3-arm, parallel group, multicenter study. Subjects received 200 µg ciclesonide, 5 mg levocetirizine, or a combination of both. Changes from baseline until the end-of-study visit (2 weeks following) were evaluated by reflective total nasal symptom scores (rTNSSs), reflective total ocular symptom scores (rTOSSs), physician-assessed overall nasal signs and symptoms severity (PANS), and rhinoconjunctivitis quality-of-life questionnaires (RQLQ).ResultsSignificant improvements in rTNSS, PANS, and RQLQ in the ciclesonide monotherapy group were observed in comparison to the levocetirizine alone group. Three individual symptoms of rTNSS, including runny nose, nasal itching, and congestion, were improved in the ciclesonide-treated group. rTOSS scores for ciclesonide monotherapy improved from baseline, but no superiority over levocetirizine was shown. The absolute score and changes in rTNSS and PANS were positively correlated. Ciclesonide spray was more effective than levocetirizine in reducing nasal symptoms in both SAR and PAR patients. Ciclesonide and levocetrizine were well tolerated alone and in combination.ConclusionsOur results provide support for an AR and its Impact on Asthma (ARIA) recommendation stipulating that ciclesonide is superior to levocetirizine for the treatment of AR, with tolerable safety. Addition of levocetirizine to ciclesonide did not give further clinical benefit over monotherapy.

Comparison of Intranasal Ciclesonide, Oral Levocetirizine, and Combination Treatment in Patients with Allergic Rhinitis

Objectives: Ciclesonide is an intranasal corticosteroid for the treatment of allergic rhinitis. To date, concrete evidence to justify a definitive recommendation of intranasal corticosteroid over oral antihistamine has not been demonstrated. This study aimed to evaluate the efficacy and safety of once-daily ciclesonide in comparison to both levocetirizine alone, and a ciclesonide/levocetirizine combination in patients with seasonal (SAR) and perennial AR (PAR). Methods: Subjects exhibiting moderate to severe allergic rhinitis for longer than 1 year were randomized in an open-label, 3-arm, parallel group, multicenter study. Subjects received 200 µg ciclesonide, 5 mg levocetirizine, or a combination of both. Changes from baseline until the end-of-study visit (2 weeks following) were evaluated by reflective total nasal symptom scores (rTNSS), reflective total ocular symptom scores (rTOSS), physician-assessed overall nasal signs and symptoms severity (PANS), and rhinoconjunctivitis quality-of-life questionnaires (RQLQ). Results: Significant improvements in rTNSS, PANS, and RQLQ in the ciclesonide monotherapy group were observed in comparison to the levocetirizine alone group. Three individual symptoms of rTNSS were improved in the ciclesonide-treated group. rTOSS scores for ciclesonide monotherapy improved from baseline, but no superiority over levocetirizine was shown. Ciclesonide spray was more effective than levocetirizine in reducing nasal symptoms in both SAR and PAR patients. Ciclesonide and levocetrizine were well tolerated alone and in combination. Conclusions: Our results provide support for an AR and its Impact on Asthma (ARIA) recommendation stipulating that ciclesonide is superior to levocetirizine for the treatment of AR, with tolerable safety. Addition of levocetirizine to ciclesonide did not give further clinical benefit over monotherapy.

Growth Velocity Reduced with Once-Daily Fluticasone Furoate Nasal Spray in Prepubescent Children with Perennial Allergic Rhinitis

The effect of fluticasone furoate nasal spray (FFNS) on growth in prepubescent children has not been evaluated. To characterize the difference in mean prepubescent growth velocities, as determined by stadiometry, between patients treated continuously for 1 year with FFNS 110mcg once daily and placebo nasal spray. This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group 76-week safety study. Nasal symptom assessments were used as a measure of adherence. Eligible patients were ages 5 to <8.5 years at screening and had at least a 1-year clinical history and diagnosis of perennial allergic rhinitis, including a positive skin test or specific IgE to an appropriate perennial allergen within the past year. One hundred eighty-six patients in the FFNS group and 187 patients in the placebo group completed the entire 52-week treatment period. During treatment, the least squares mean growth velocity was 5.19 cm/y for the FFNS group and 5.46 cm/y for the placebo group; mean difference,-0.270 cm/y (95% CI,-0.48 to-0.06 cm/y). Other safety assessments, including 24-hour urinary cortisol excretion, were comparable between the treatment groups. Daily reflective total nasal symptom scores declined similarly in both the FFNS and placebo groups. Once-daily treatment with FFNS over 52 weeks in prepubescent children resulted in a small reduction in growth velocity compared with placebo. Clinicians will need to balance the reduction in growth observed with FFNS to its potential for clinical benefit.

Effect of intranasal triamcinolone acetonide on basal hypothalamic‐pituitary‐adrenal axis function in children with allergic rhinitis

Intranasal corticosteroids are the most effective medication class for controlling allergic rhinitis (AR) symptoms. However, limited data are available on their effects on basal hypothalamic-pituitary-adrenal (HPA) axis function in children. This study was designed to determine the effect of 6-week triamcinolone acetonide aqueous (TAA-AQ) nasal spray treatment on HPA axis function by measuring 24-hour serum cortisol area under the curve (AUC(0-24h)) in children with AR aged 2-11 years. This phase 4, multicenter, double-blind, placebo-controlled, parallel-group study randomized children with AR to receive TAA-AQ (110 μg, 2-11 years old, or 220 μg, 6-11 years old) or placebo. At pre- and posttreatment domiciled visits, 24-hour serum cortisol and reflective total nasal symptom scores (rTNSSs) were assessed. Safety assessment included treatment-emergent adverse events (TEAEs) at each visit and trough levels of 24-hour serum cortisol. A total of 140 subjects (mean age, 7.2 years; males, 59%) were randomized; 66 from each group completed treatment. The ratio of TAA-AQ to placebo for change from baseline in serum cortisol AUC(0-24h) was 0.966 (95% confidence interval, 0.892-1.045). Reduction from baseline in mean rTNSS was significantly greater in the TAA-AQ than in the placebo group (difference: least square mean ± SE = -0.85 ± 0.24; p = 0.0007). The safety profile was similar (TEAEs, TAA-AQ, 27.5%; placebo, 25.4%), and so was the mean change in serum cortisol trough level (TAA-AQ, -0.4 μg/dL; placebo, -0.1 μg/dL; p = 0.1818 for treatment difference) from pre- to posttreatment. TAA-AQ was safe, well tolerated, and not associated with clinically meaningful suppression of serum cortisol AUC(0-24h) in children with AR. Clinical trial NCT01154153, www.clinicaltrials.gov.

Allergic Rhinitis (AR) Is Sub-Optimally Controlled: The Need For a More Effective Treatment Option

AR remains sub-optimally controlled. Our aim was to (i) use patient survey data to explore the unmet need in AR, and (ii) show how a new treatment option (MP29-02; Dymista), a novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP) in an advanced delivery system can fill this need. AR symptomatology and medication usage data were collected from 746 moderate/severe seasonal AR (SAR) patients who completed a healthcare utilization survey in the UK. The patient characteristics mimicked those of patients in the MP29-02 clinical trials. The clinical efficacy of MP29-02 was compared to commercially available AZE or FP nasal sprays and placebo in a 14-day randomized controlled trial including 610 SAR patients. Time to response was assessed post-hoc. A ≥30% to ≥90% change from baseline in reflective total nasal symptom score (rTNSS) defined response. 96.2% of patients surveyed were on AR medication; 70.5% taking ≥2 medications. These patients remained symptomatic with a mean rTNSS of 12.8 (range 0-24) and a mean rTOSS of 8.6 (range 0-18). Clinical trial data in a matched population showed that more MP29-02-patients achieved ≥30%, ≥50%, ≥60%, ≥75% and ≥90% rTNSS-reduction, and days faster than either active comparator. FP did not differ from placebo in providing a ≥60% rTNSS reduction. AR is often poorly controlled with current therapies (even multiple therapies). Intranasal corticosteroids fail to provide sufficient symptom control in many patients. Treatment with MP29-02 addresses this unmet medical need as it provides faster and more complete symptom control than FP.

Efficacy and safety of beclomethasone dipropionate nasal aerosol in pediatric patients with seasonal allergic rhinitis

BackgroundAerosolized intranasal corticosteroid formulations are desirable for many patients with allergic rhinitis (AR), especially children, who wish to avoid the “wet feeling” and “drip down the throat” associated with aqueous formulations. Beclomethasone dipropionate (BDP) hydrofluoroalkane nasal aerosol has been shown to be safe and effective in adolescents and adults with AR. ObjectiveTo evaluate the efficacy and safety of BDP nasal aerosol in pediatric patients with moderate to severe seasonal AR. MethodsIn this double-blinded, placebo-controlled study, children (6–11 years of age) with seasonal AR were randomized to once-daily treatment with BDP nasal aerosol 80 μg (n = 239) or 160 μg (n = 242) or placebo (n = 234). The primary end point was change from baseline in average morning and evening reflective total nasal symptom score over the 2-week treatment period. ResultsTreatment with BDP nasal aerosol showed significantly greater improvements in average morning and evening reflective total nasal symptom score vs placebo (80 μg, −0.71; 160 μg, −0.76; P < .001 for the 2 comparisons). Similarly, significantly greater improvements in average morning and evening instantaneous total nasal symptom score were seen with BDP nasal aerosol vs placebo (80 μg, −0.63; 160 μg, −0.73; P < .001 for the 2 comparisons). The incidence of adverse events from BDP nasal aerosol was comparable to that from placebo. ConclusionBDP nasal aerosol (80 or 160 μg/d) provided significant and clinically meaningful nasal symptom relief and an established overall safety profile similar to that of placebo, suggesting that it is an effective and well-tolerated treatment option for pediatric patients with moderate to severe seasonal AR. Trial Registrationclinicaltrials.gov Identifier: NCT012073190.

Efficacy, safety, and optimal dose selection of beclomethasone dipropionate nasal aerosol for seasonal allergic rhinitis in adolescents and adults

Objective:Some patients with allergic rhinitis (AR) may prefer nonaqueous intranasal corticosteroid aerosols because of unwanted attributes of aqueous formulations. The mandatory removal of chlorofluorocarbon-propelled nonaqueous aerosols from the market limited available treatment options. To fulfill this unmet need, a nonaqueous, hydrofluoroalkane-propelled beclomethasone dipropionate (BDP) nasal aerosol was developed and approved for treatment of AR nasal symptoms. As part of the development program, this dose-ranging study evaluated three doses of BDP nasal aerosol to determine the optimally safe and effective dose for adolescent and adult patients (≥12 years old) with seasonal AR (SAR).Methods:After a 7 to 21 day placebo run-in period, eligible patients with SAR were randomly assigned to once-daily BDP nasal aerosol 80 µg, 160 µg, 320 µg, or placebo. The primary endpoint was the change from baseline in average a.m. and p.m. patient-reported reflective total nasal symptom scores (rTNSS) over 2 weeks. Safety and tolerability were also assessed. A potential study limitation could be lack of objective assessment of AR symptoms.Results:Significant improvements were seen in average a.m. and p.m. rTNSS (least squares [LS] mean treatment difference, −0.63; 95% CI: −1.13, −0.13; p = 0.013) as well as in average a.m. and p.m. instantaneous TNSS (iTNSS; LS mean treatment difference, −0.60; 95% CI: −1.09, −0.11; p = 0.016) with BDP nasal aerosol 320 µg/day compared with placebo. Although there were numerical improvements from baseline in patient-reported rTNSS and iTNSS with BDP nasal aerosol 80 µg and 160 µg, these doses did not achieve statistical significance compared with placebo. BDP nonaqueous nasal aerosol was well tolerated at all doses tested, with a safety profile comparable to that of placebo.Conclusions:These data indicate that 320 µg/day of BDP nasal aerosol is the optimally safe and effective dose for the treatment of SAR in adolescent and adult patients.Trial registration NCT:#NCT00854360.

A new therapy (MP29‐02*) effectively targets the entire seasonal allergic rhinitis symptom complex

Background Over 90% of allergic rhinitis (AR) patients have ocular symptoms during the pollen season, but these are routinely neglected and under-treated. New treatment options should provide relief not only from all nasal symptoms, but all ocular symptoms too, since patients frequently present with symptoms from both nasal and ocular origin. The reflective total of 7 symptom scores (rT7SS) is an endpoint measuring the entire AR symptom complex. It comprises both the reflective total nasal symptom score (rTNSS) and the reflective total ocular symptom score in one global score (max score=42). Objective To assess the efficacy of MP29-02* (a novel intranasal formulation of azelastine hydrochloride [AZE] and fluticasone propionate [FP]) in providing relief from the entire AR symptom complex compared to commercially available intranasal AZE or FP nasal sprays and placebo, in patients with seasonal AR (SAR). Methods 610 patients (>=12 years old) with moderate-to-severe SAR were randomized into this double-blind, placebocontrolled, 14-day, parallel-group trial to MP29-02*, commercially-available AZE or FP nasal sprays, and placebo (all given as 1 spray/nostril bid [total daily doses: AZE = 548 µg; FP=200 µg]. The primary efficacy variable was change from baseline in rTNSS (AM +PM), over 14-days. Change from baseline in rT7SS was assessed post-hoc via an analysis of covariance. Results MP29-02* most effectively treated the entire rhinitis symptom complex, reducing the rT7SS from baseline by -8.74 compared to -6.05 for FP (Diff: -2.69; 95% CI: -4.33, -1.06; p=0.0013), -5.83 for AZE (Diff -2.91; 95% CI: -4.52, -1.31; p=0.0004) and -3.55 for placebo (Diff -5.19; 95% CI: -6.71, -3.68; p<0.0001). The relative difference was 52% to FP and 56% to AZE, making MP2902* twice as effective as either firstline therapy. This benefit was observed during the first day of treatment and was sustained over the entire course of treatment. Conclusion Compared to currently available first-line therapy for AR, MP29-02* most effectively treats the entire rhinitis symptom complex, comprising the most commonly reported nasal and ocular symptoms. Such a universal treatment option should preclude the need for concomitant eye drops, and may be considered the drug of choice for AR management. *Dymista

A new efficacy parameter (complete/near complete symptom relief) in allergic rhinitis management: results with a new therapy MP29‐02*

Background It is unclear what constitutes a clinically-meaningful response for allergic rhinitis (AR) outcomes. In a recent survey [1] most experts defined control as being “hardly troubled at all” by each symptom. We propose an ew criterion of ≤1 point remaining in each nasal symptom score (Max AM+PM score for each symptom=6) of the reflective total nasal symptom score (rTNSS) to stringently test efficacy and provide an endpoint meaningful to physicians and patients. This criterion has been termed complete/near-to-complete symptom control. Any treatment providing this level of control (patients will feel “cured”) should have considerable socioeconomic impact. Objective To compare the proportion of patients achieving ≤1 point remaining in each of the 4 symptoms of the rTNSS (congestion, itching, rhinorrhoea & sneezing) and the time taken to achieve this response in patients treated with MP29-02* (a novel intranasal formulation of azelastine hydrochloride [AZE] and fluticasone propionate [FP]), FP, AZE or placebo (PLA) nasal sprays. Methods 610 patients (≥12 years old) with moderate-to-severe seasonal AR were randomized into a double-blind, placebocontrolled, 14 day parallel-group trial to receive MP2902*, commercially-available AZE or FP nasal sprays or PLA nasal spray (all 1 spray/nostril bid; total daily dose [AZE: 548µg, FP: 200µg]). The primary outcome was change from baseline in rTNSS over 14-days. Time to achieve ≤1 point remaining in each nasal symptom (AM + PM) of the rTNSS was assessed post-hoc by Kaplan-Meier estimates and log rank tests. Results 17.8% of MP29-02* patients (1 out of 6) achieved this response versus 8.3%, 9.2% and 7.8% of those treated with AZE, FP and PLA, respectively. MP29-02* patients achieved this response up to 7 days faster than AZE (p=0.0152) and up to 8 days faster than either FP (p=0.0262) or PLA (p=0.0094). Neither AZE nor FP differed from PLA for this parameter.

Clinically Relevant Effect of a New Intranasal Therapy (MP29-02) in Allergic Rhinitis Assessed by Responder Analysis

Background: It is unclear what constitutes a clinically meaningful response for allergic rhinitis (AR) outcomes. The objectives of these post hoc analyses were (1) to define a clinically meaningful response using novel efficacy analyses (including a responder analysis), and (2) to compare the efficacy of MP29-02 [a novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP)] with commercially available FP, AZE and placebo in seasonal AR (SAR) patients, using these novel analyses. Methods: 610 moderate-to-severe SAR patients (≥12 years old) were randomized into a double-blind, placebo-controlled, 14-day, parallel-group trial. Change from baseline in the reflective total nasal symptom score (rTNSS) over 14 days was the primary outcome. Post hoc endpoints included the sum of nasal and ocular symptoms (rT7SS), efficacy by disease severity and by predominant nasal symptom, and a set of responder analyses. Results: MP29-02 most effectively reduced rT7SS (relative greater improvement: 52% to FP; 56% to AZE) and both nasal and ocular symptoms irrespective of severity. More MP29-02 patients achieved a ≥30, ≥50, ≥60, ≥75 and ≥90% rTNSS reduction, which occurred days faster than with either active comparator; MP29-02 alone was superior to placebo at the ≥60% (or higher) threshold. One in 2 MP29-02 patients achieved a ≥50% rTNSS reduction and 1 in 6 achieved complete/near-to-complete response. Only MP29-02 was consistently superior to placebo for all patients, whatever their predominant symptom. Conclusions: MP29-02 provided faster and more complete symptom control than first-line therapies. It was consistently superior irrespective of severity, response criteria or patient-type, and may be considered the drug of choice for moderate-to-severe AR. These measures define a new standard for assessing relevance in AR.

An integrated analysis of the efficacy of fluticasone furoate nasal spray versus placebo on the nasal symptoms of perennial allergic rhinitis

Intranasal corticosteroids are widely prescribed for the treatment of perennial allergic rhinitis (PAR). The aim of this analysis was to determine whether the beneficial effects of once-daily (q.d.) fluticasone furoate nasal spray (FFNS) effectively improved individual nasal symptoms of PAR. An integrated analysis was performed on data from three randomized, double-blind, placebo-controlled, parallel-group trials designed to evaluate the efficacy and safety of FFNS at 110 micrograms, q.d. in subjects with PAR. The analysis included 460 subjects who received FFNS and 459 who received placebo for 4 weeks. All subjects evaluated the severity of individual nasal symptoms of nasal congestion, nasal itching, rhinorrhea, and sneezing on a four-point categorical scale. The main efficacy measures included change from baseline in daily reflective total nasal symptom score (rTNSS), reflective daily scores for each individual symptom, and predose instantaneous TNSS (iTNSS). Over 4 weeks of treatment, FFNS significantly improved rTNSS, iTNSS, and the reflective scores for each individual symptom compared with placebo. The least squares (LS) mean treatment difference over weeks 1-4 between FFNS and placebo for rTNSS was -0.93, ranging from -0.20 to -0.28 for the individual nasal symptoms (p < 0.001 for all versus placebo). For the iTNSS, the LS mean treatment difference between FFNS and placebo over weeks 1-4 was -0.95 (95% CI,-1.24, -0.66; p < 0.001). FFNS at 110 micrograms q.d. effectively relieved all nasal symptoms of PAR including nasal congestion over a 24-hour period.

Once-Daily Treatment with Beclomethasone Dipropionate Nasal Aerosol Provides Long-Term and Sustained 24-Hour Nasal Symptom Relief in Patients with Perennial Allergic Rhinitis

Patients with perennial allergic rhinitis (PAR) suffer from nasal symptoms requiring year-round treatment. Symptoms are often most severe in the morning, making 24-hour duration of effect a critical component of once-daily treatments. This study assessed the 24-hour duration of nasal symptom relief following treatment with a nonaqueous, hydrofluoroalkane-propelled aerosol formulation of beclomethasone dipropionate (BDP nasal aerosol). In this double-blind, placebo-controlled study, eligible patients (≥12 years of age) were randomly assigned 4:1 to once-daily treatment with BDP nasal aerosol 320 μg or placebo. The primary efficacy measure was patient-reported 24-hour reflective total nasal symptom score (rTNSS) over the first 30 weeks (previously reported). Weekly averages of patient-reported am instantaneous TNSS (iTNSS) over the entire 52-week treatment period were also assessed and reported here. BDP nasal aerosol resulted in greater improvements in weekly patient-reported am iTNSS compared with placebo from week 1, which were maintained through 52 weeks of treatment. The least-square mean treatment differences from placebo for BDP nasal aerosol ranged from a minimum of –0.60 (P<0.001) at week 1 to a maximum of –1.33 (P=0.005) at week 40, and the effect was maintained to week 52 (–1.15; P=0.019). BDP nasal aerosol was well tolerated during long-term treatment, and the overall safety profile was comparable to that of placebo. The clinically meaningful improvements in morning instantaneous total nasal symptom score reported in this 52-week study support both the 24-hour and long-term sustained efficacy of once-daily BDP nasal aerosol 320 μg for the treatment of PAR.