Reflective Total Ocular Symptom Score Research Articles

Efficacy and safety of stapokibart (CM310) in uncontrolled seasonal allergic rhinitis (MERAK): an investigator-initiated, placebo-controlled, randomised, double-blind, phase 2 trial

There is no trial to assess the benefits of periodically using biologics during the pollen season in patients with uncontrolled seasonal allergic rhinitis (SAR), who have moderate-to-severe symptoms even after standard-of-care. This trial aimed to evaluate the efficacy and safety of the add-on administration of stapokibart, a humanised monoclonal antibody that targets interleukin-4 receptor alpha, in patients with uncontrolled SAR. In this investigator-initiated, randomised, double-blind, placebo-controlled trial, eligible patients received either stapokibart 600-300mg weekly (QW), every 2 weeks (Q2W), or placebo QW for 4 weeks. All patients were given mometasone furoate nasal spray and loratadine throughout the trial. The primary endpoint was the mean change from baseline in daily reflective total nasal symptom score (rTNSS) during 2-week treatment. Secondary efficacy outcomes included: the mean change from baseline in daily rTNSS during 4-week treatment; the mean changes and the mean percentage changes from baseline during 2-week and 4-week treatment in 1) daily rTNSS and reflective total ocular symptom score (rTOSS), 2) morning (AM)/evening (PM) rTNSS and rTOSS, 3) AM instantaneous total nasal symptom score (iTNSS) and instantaneous total ocular symptom score (iTOSS), 4) individual nasal and ocular symptoms; the change from baseline in Rhinoconjunctivitis Quality of-Life Questionnaire score during 4-week treatment. Exploratory endpoints included the change of prespecified markers related to type 2 inflammation pre- and post-treatment. Safety, immunogenicity, and pharmacokinetics were also evaluated. This study is registered with www.clinicaltrials.gov (NCT05470647). Between August 17, 2022, and December 28, 2022, 92 patients with uncontrolled SAR were enrolled from 4 centres in China and randomly assigned to receive stapokibart 600-300mg QW (n=31), stapokibart 600-300mg Q2W (n=30), or placebo QW (n=31), of whom 86 (93%) completed the study. Both stapokibart Q2W and QW did not significantly improve mean change from baseline in daily rTNSS compared with placebo in 2 weeks. The least-squares (LS) mean differences (97.5% confidence interval [CI]) compared with placebo were-1.0 (-2.3, 0.2) in stapokibart Q2W group (p=0.065) and-0.2 (-1.5, 1.0) in stapokibart QW group (p=0.67). For the secondary outcomes, compared with placebo, stapokibart Q2W presented significant improvements in the mean percentage change from baseline in daily rTNSS in 2 weeks (LS mean difference-12.9%, 95% CI-25.3%,-0.4%, p=0.043), as well as AM iTNSS over 2 weeks (LS mean difference-17.4%, 95% CI-31.0%,-3.8%, p=0.013) and 4 weeks (LS mean difference-15.4%, 95% CI-29.0%,-1.9%, p=0.026). Additionally, the nasal congestion score was significantly lower in stapokibart Q2W than placebo during 2-week (LS mean difference-0.4, 95% CI-0.7,-0.1, p=0.014) and 4-week (LS mean difference-0.4, 95% CI-0.7,-0.04, p=0.028) treatment. Treatment-emergent adverse events (TEAEs) occurred in 48% (15/31), 33% (10/30), and 61% (19/31) of patients receiving stapokibart QW, Q2W, and placebo, respectively. Most reported TEAEs were sinus bradycardia, hyperlipidaemia, and blood uric acid increased. In this phase 2 trial, both stapokibart regimens had an acceptable safety and tolerability profile but did not significantly improve daily rTNSS in patients with uncontrolled SAR. The efficacy of stapokibart in patients with uncontrolled SAR is being further investigated in ongoing phase 3 trials (clinicaltrials.gov, NCT05908032). Ministry of Science and Technology of the People's Republic of China; Ministry of Education of the People's Republic of China; National Natural Science Foundation of China; Chinese Academy of Medical Sciences.

Effect of acupuncture therapy combined with fluticasone propionate in the treatment of persistent allergic rhinitis: study protocol for a randomized controlled trial

BackgroundAllergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated inflammatory response.Persistent allergic rhinitis (PAR) is a subtype of AR, but the treatment of PAR is still a problem. Acupuncture is used as an alternative therapy for AR in clinical practice. The aim of this study is to evaluate the effectiveness of acupuncture therapy combined with fluticasone propionate nasal spray in comparison to fluticasone propionate nasal spray alone in the relief of symptoms for PAR.MethodsThis study is a multicenter, single-blind, randomized controlled trial. A total of 260 eligible patients will be randomly assigned into the treatment group or the control group. The treatment group will receive the nasal fluticasone propionate combined with acupuncture, and the control group will receive fluticasone propionate nasal spray alone for 6 weeks. The primary outcome is the change in the Reflective Total Nasal Symptom Score (rTNSS) from baseline to the end of treatment, and the Total Non Nasal Symptom Score (TNNSS), reflective total ocular symptom score (rTOSS), Rhinitis Quality of Life Questionnaire (RQLQ), use of antiallergic drugs, and the Rhinitis Control Assessment Test (RCAT) are used as secondary outcomes. The participants will be followed up for another 24 weeks after treatment.DiscussionThis clinical trial will be able to provide high level evidence on the acupuncture therapy combined with fluticasone propionate nasal spray in the treatment of PAR.Trial registrationISRCTN Registry, ID: ISRCTN44040506. Registered on 22 July 2020.

Conception and Clinical Efficacy of an Osmotic, Polymeric, Stable Nasal Filmogen Barrier for Preventive Treatment of Allergen and Pollution Induced Rhinitis and Respiratory Symptoms

Background: Pollution induced allergic rhinitis and respiratory symptoms is becoming a major health problem in the world for which still there is no safe and preventive treatment. Objectives: Conceive and evaluate the allergen preventive properties and clinical efficacy of an osmotic, polymeric, stable filmogen spray, called PCNS. Materials and Methods: Amb A 1 (ragweed), Der P 1 and 2 (dust mite), Bet v 1 (birch), Alt a 1 (Alternaria, fungus), and Fel d 1 (cat dander) allergens were exposed at a concentration of 5µg/ml (20 µl per tube) on the polymeric test product film (120 and 240µl layer) and the allergens crossing the barrier were quantified in the agar gel beneath the film. 0.40% HPMC and PBS solutions, tested identically, served as controls. Clinical efficacy of PCNS nasal spray was evaluated in patients suffering from allergic rhinitis and/or respiratory symptoms (29 in test product v/s 15 in saline controls) for 22 days. Nasal, ocular, respiratory symptoms and Rhino conjunctivitis Quality of Life Questionnaire (RQLQ) were measured. Statistical analyses: The normality of the populations was determined by the Shapiro-Wilk test, then statistical analysis was performed by two-tailed Student’s test for comparisons between two groups and the two-way ANOVA followed by the post hoc Bonferroni’s test for comparisons of multiple groups. p<0.05 was considered statistically significant. The analyses were performed with the software GraphPad Prism (version 8.4.2, La Jolla, USA). NS indicates not significant. Results: PCNS polymeric spray blocked the diffusion of all the allergens while 0.40% HPMC was able to prevent diffusion of only Alt a 1 and Fel d 1 allergens. Mean reflective total nasal symptom scores (rTNSS), reflective total ocular symptom score (rTOSS), and respiratory symptoms including effect on wheezing, cough, dyspnea, and chest tightness were moderately improved in the control saline group, but the improvements were nearly twice better in the PCNS group. RQLQ was improved by 23% in saline spray v/s 46% PCNS group. 4/15 patients in saline group v/s 1/29 in PCNS group required rescue medication during the study. PCNS was highly effective in reducing allergen and pollution induced respiratory symptoms. Conclusion: a polymeric, osmotic, and stable nasal barrier against pollutants and allergens represents an innovative approach against pollution induced respiratory symptoms.

Efficacy and safety of twice-daily olopatadine-mometasone combination nasal spray (GSP301) in the treatment of allergic rhinitis: a systematic review and meta-analysis.

GSP301 is a fixed-dose combination of olopatadine hydrochloride (antihistamine) and mometasone furoate (corticosteroid). This meta-analysis aims to evaluate the efficacy and safety of GSP301 in the treatment of allergic rhinitis. A systematic review and meta-analysis were conducted. The data were collected from PubMed, Cochrane Central Register of Controlled Trials and Embase databases till June 2021. In patients with AR, short-term (2/6weeks) and long-term (52weeks) effects of GSP301 were assessed. Average morning and evening 12-h reflective total nasal symptom score (rTNSS), instantaneous total nasal symptom score (iTNSS), reflective total ocular symptom score (rTOSS), instantaneous total ocular symptom score(iTOSS), Physician-assessed nasal symptom score (PNSS), rhinoconjunctivitis quality of life (RQLQ), rhinitis control assessment test (RCAT) and adverse events (AEs) were measured. Five randomized controlled trials were included. GSP301 showed greatly improvement in rTNSS (MD = - 0.99; [95% CI - 1.19 to - 0.79]; P < 0.01; I2 = 0), iTNSS (MD = - 1.05; [95% CI - 1.44 to - 0.67]; P < 0.01; I2 > 50%), rTOSS (MD = - 0.50; [95% CI - 0.72 to - 0.29]; P < 0.01; I2 = 0), iTOSS (MD = - 0.64; [95% CI - 1.02 to - 0.26]; P < 0.01; I2 > 50%), PNSS (MD = - 1.01; [95% CI - 1.32 to - 0.69]; P < 0.01; I2 = 22.13%), RQLQ (MD = - 0.43; [95% CI - 0.57 to - 0.30]; P < 0.01; I2 = 0%) and RCAT (MD = 1.94; [95% CI 1.43-2.45]; P < 0.01; I2 = 0%) in the short term. No statistical difference was observed in the outcome of long-term PNSS, RQLQ and RCAT. GSP301 is a safe and well-tolerated medication. It showed short-term benefits for seasonal and perennial AR, but may not help to improve patients' quality of life and rhinitis control in the long run.

Clinical efficacy and safety of MP-AzeFlu for the treatment of allergic rhinitis: a meta-analysis.

MP-AzeFlu is a novel option for therapy of allergic rhinitis (AR). The purpose of our study was to assess the safety and efficacy of MP-AzeFlu for the treatment of allergic rhinitis, compared to placebo and azelastine monotherapy. The PubMed, MEDLINE, EMBASE and Cochrane databases were comprehensively searched for all published randomized controlled trials (RCTs) of using MP-AzeFlu nasal spray on July 26, 2019. In these studies, we selected patients with clinical symptom scores. The heterogeneity of the included studies was assessed by I2. Among the 336 citations retrieved, 6 articles with over 6000 patients were finally included in the meta-analysis. The results of meta-analysis revealed that MP-AzeFlu was superior to placebo (-2.43 [95%CI, -2.73 to -2.14], P < 0.00001) and azelastine (-1.27 [95% CI, -1.57 to -0.97], P < 0.00001) in reflective total nasal symptom score. In the MP-AzeFlu group, the instantaneous total nasal symptom score (-2.56 [95% CI, -3.02 to -2.10], P < 0.00001) and the reflective total ocular symptom score (-1.22 [95% CI, -1.57 to -0.87], P < 0.00001) were significantly reduced compared to the placebo group. MP-AzeFlu is as safe and mild as placebo and azelastine, which also is associated with symptom relief and the improvement of quality of life in AR patients. MP-AzeFlu can provide better clinical benefits than two currently available first-line intranasal therapies. It is an ideal therapy for AR patients.

Validation of the DECA criteria for allergic conjunctivitis severity and control

BackgroundAllergic conjunctivitis (AC) is usually associated to allergic rhinitis (AR), but the severity and control of ocular symptoms should be assessed independently to improve diagnosis and treatment. The criteria from the Spanish consensus document on allergic conjunctivitis (DECA) aimed to be used as a patient-reported instrument for AC management. Here we validate these criteria for classifying AC severity and defining its control following COSMIN guidelines recommendations.MethodsPatients with moderate or severe AR [reflective total nasal symptom score (rTNSS) score ≥ 8] and concomitant AC were recruited from hospitals in Spain. Patients were classified according to the severity of ocular symptoms as mild, moderate, or severe, and classified with respect to control as controlled and non-controlled, using the DECA criteria. To validate these criteria, comparisons with the validated modified allergic rhinitis and its impact on asthma (mARIA), reflective total ocular symptom score (rTOSS), rhinitis control assessment test (RCAT), ESPRINT-15 questionnaires, a conjunctival hyperemia scale and a visual analogue scale (VAS) for ocular symptoms were performed.ResultsA total of 128 patients participated in the validation. Mean age was 34.4 ± 12.1 years; 72.7% were women. The DECA criteria showed a good discriminant validity, reflecting a high capacity to differentiate between mild, moderate, and severe patients, and controlled from uncontrolled patients. A strong association between AC and AR was reflected in the comparison between the DECA and the mARIA criteria (p < 0.0001). The DECA criteria for severity and control presented satisfactory properties for longitudinal validity and responsiveness.ConclusionsValidation of the DECA criteria for severity and control of AC suggested that it can be useful in the evaluation of eye symptoms and follow-up of therapies.

Olopatadine-mometasone combination nasal spray: Evaluation of efficacy and safety in patients with seasonal allergic rhinitis.

Background: GSP301 is an investigational fixed-dose combination nasal spray that contains the antihistamine, olopatadine hydrochloride (HCl), and the corticosteroid, mometasone furoate. Objective: To evaluate the efficacy and safety of GSP301 in patients with seasonal allergic rhinitis (SAR). Methods: In this double-blind, randomized, parallel-group study, patients (≥12 years of age) with SAR were equally randomized to intranasal GSP301 (olopatadine 665 μg and mometasone 25 μg), olopatadine HCl (665 μg), mometasone furoate (25 μg), or placebo for 14 days of twice-daily treatment. The primary end point was the mean change from baseline in the average A.M. and P.M. 12-hour reflective Total Nasal Symptom Score (rTNSS) analyzed by using mixed-effect model repeated measures (p < 0.05 indicates statistical significance). Additional assessments included instantaneous TNSS (iTNSS), individual nasal symptoms, reflective Total Ocular Symptom Score (rTOSS) and instantaneous Total Ocular Symptom Score (iTOSS), onset of action, Physician-assessed Nasal Symptom Score (PNSS), quality of life, and adverse events (AE). Results: A total of 1180 patients were randomized. Over 14 days of treatment, GSP301 significantly improved average A.M. and P.M. rTNSS versus placebo (least squares mean difference -0.98 [95% confidence interval, -1.38 to -0.57]; p < 0.001) and versus olopatadine (p = 0.003), and approached statistical significance versus mometasone (p = 0.059). GSP301 also significantly improved average A.M. and P.M. iTNSS versus placebo and both monotherapies (p < 0.05, all). Further, GSP301 significantly improved individual nasal symptoms, overall ocular symptoms (rTOSS and iTOSS), and overall quality of life versus placebo (p < 0.01, all). Onset of action for GSP301 was observed within 15 minutes and was maintained at all subsequent time points assessed. Results for the PNSS also were significant for GSP301 versus placebo (p < 0.001). The percentages of patients with treatment-emergent AEs treated with GSP301, olopatadine, mometasone, and placebo were 12.9, 12.5, 7.1, and 9.4%, respectively. Conclusion: GSP301 was efficacious and well tolerated for the treatment of SAR symptoms compared with placebo, with a rapid onset of action of 15 minutes in patients ≥12 years of age.Clinical trial NCT02631551, <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov">www.clinicaltrials.gov</ext-link>.

Efficacy of a Novel Intranasal Formulation of Azelastine Hydrochloride and Fluticasone Propionate, Delivered in a Single Spray, for the Treatment of Seasonal Allergic Rhinitis: Results from Russia

Background: The novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP) in a single spray (MP-AzeFlu) was compared with a first-line intranasal antihistamine spray (AZE) in Russian seasonal allergic rhinitis (SAR) patients. Methods: Moderate-to-severe SAR/rhinoconjunctivitis patients (n = 149; aged 18–65 years) were randomized to receive MP-AzeFlu (137/50 μg AZE/FP per spray) or AZE (137 μg/spray), both as 1 spray/nostril twice daily, in a multicenter, open-label, 14-day, parallel-group trial. The primary outcome was change from baseline in morning and evening reflective total nasal symptom score (rTNSS). Secondary end points included: change from baseline in reflective total ocular symptom score (rTOSS), reflective total of 7 symptom scores (rT7SS), 28-item Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) overall score, and EuroQol-5D (EQ-5D) questionnaire score. Results: When compared with AZE-treated patients, those treated with MP-AzeFlu experienced significantly greater reductions in rTNSS (difference: –2.47; 95% confidence interval [CI] –3.65 to –1.30; p < 0.001), rTOSS (difference: –1.62; 95% CI –2.32 to –0.92; p < 0.001), and rT7SS (difference: –4.34; 95% CI –5.98 to –2.70; p < 0.001). Superior relief observed on day 2 with MP-AzeFlu versus AZE was sustained throughout the study. MP-AzeFlu-treated patients experienced a greater improvement in QoL than AZE-treated patients as measured by overall RQLQ score (mean ± SD 2.91 ± 1.08 vs. 2.05 ± 1.15) and EQ-5D score (mean ± SD 87.4 ± 10.3 vs. 83.0 ± 12.8). MP-AzeFlu was well tolerated. Conclusions: MP-AzeFlu was superior to AZE in reducing moderate-to-severe SAR symptoms, providing earlier and more complete symptom relief.

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.

Efficacy of daily intranasal fluticasone propionate on ocular symptoms associated with seasonal allergic rhinitis

BackgroundAllergic rhinitis (AR) is an inflammatory condition of the nasal mucosa characterized by symptoms of nasal discharge, itching, sneezing, and congestion. Ocular symptoms are commonly associated with AR and include itching or burning, tearing or watering, and redness. Intranasal corticosteroids are a mainstay of treatment, and their effect on nasal symptoms is well described. ObjectiveTo demonstrate that a 14-day course of 200 μg/d of nasal fluticasone propionate is superior to placebo in relieving ocular symptoms associated with AR. MethodsThis was a randomized, double-blind, parallel group, multicenter study comparing 200 μg/d of fluticasone propionate with placebo in patients with seasonal allergic rhinitis. The primary end point was mean change from baseline in patient-rated reflective total ocular symptom score (rTOSS). Key secondary end points included mean change from baseline in the morning and evening rTOSS, end-of-treatment assessment of response, and effect on activities of daily living. The primary analysis was performed using analysis of covariance with a linear fixed-effects model. ResultsFluticasone was statistically significantly more efficacious in reducing the ocular symptoms of AR than placebo. The least squares mean difference in the change from baseline of rTOSS was −0.36 (P = .002). A statistically significant difference in mean change from baseline was observed in favor of fluticasone for morning and evening rTOSS. Significantly more patients taking fluticasone achieved an overall response compared with placebo. Fluticasone had a significantly greater effect on daily living activities and was well tolerated. ConclusionThis study supports the efficacy of fluticasone in treating ocular symptoms associated with AR. Trial Registrationclinicaltrials.gov Identifier: NCT01817790.

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.

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

Efficacy of Mometasone Furoate and Fluticasone Furoate on Persistent Allergic Rhinoconjunctivitis

Allergic rhinoconjunctivitis denotes both nasal and ocular manifestation of allergy, which may be solely treated with intranasal steroid. This study compares the efficacy of mometasone furoate nasal spray (NS) and fluticasone furoate NS in treatment of allergic rhinoconjunctivitis. The secondary objective is to study the severity of baseline ocular symptoms in allergic rhinoconjunctivitis. Seventy-eight patients with allergic rhinoconjunctivitis were assessed subjectively and objectively using twice-daily symptom scores for nasal (reflective total nasal symptom score [rTNSS] and instantaneous TNSS [iTNSS]) and ocular (reflective total ocular symptom score [rTOSS] and instantaneous TOSS [iTOSS]) symptoms, rhinoconjunctivitis quality-of-life questionnaires (RQOLQs), and acoustic rhinometry. All measurements were taken at baseline and at 4 and 8 weeks of treatment. Sixty-three patients who were randomized into the mometasone furoate group (n = 36) and the fluticasone furoate group (n = 27) completed the study. Seventy-six percent of patients had mild ocular symptoms, 20.5% had moderate symptoms, and only 2.6% had severe symptoms at baseline based on the iTOSS; 65.1% had mild nasal symptoms and 3% had severe nasal symptoms. There was significant reduction in the symptom scores after 1 week (p < 0.05). Both groups had significant improvement in RQOLQ scores after 1 month, which further improved at 2 months (p < 0.05). The nasal dimensions also improved in both groups (p < 0.05) but there was no statistically significant difference between groups. Both mometasone furoate and fluticasone furoate are effective as single-modality treatment of allergic rhinoconjunctivitis. The majority of patients manifest mild ocular symptoms that may be solely treated with intranasal steroids.

Comparison of intranasal azelastine to intranasal fluticasone propionate for symptom control in moderate-to-severe seasonal allergic rhinitis

Intranasal corticosteroids are considered the most effective therapy for moderate-to-severe seasonal allergic rhinitis (SAR) and recommended first line in guidelines. It is uncertain whether intranasal antihistamines have comparable efficacy. This study was designed to compare the efficacy of azelastine (AZE; 137 μg/spray) and fluticasone propionate (FP; 50 μg/spray), both given as 1 spray/nostril bid (i.e., approved dosing regimen in the United States), in SAR via a post hoc analysis of data from a previously published direct-comparison study. Six hundred ten moderate-to-severe SAR patients (≥12 years old) were randomized into a double-blind, placebo-controlled, parallel-group trial. The primary efficacy variable was change from baseline in reflective total nasal symptom score (rTNSS (morning and evening), over 14 days. Reflective total ocular symptom score (rTOSS) was a key secondary variable. Reflective total of seven symptom scores (rT7SS [nasal plus ocular symptoms]) and time to ≥50% reduction from baseline in these key parameters were also analyzed. AZE and FP reduced rTNSS from baseline by a similar degree (-3.25 versus -3.84; p = 0.2014). Patients experienced comparable improvement in rTOSS (-2.62 versus -2.17; p = 0.2371) and rT7SS (-5.83 versus -6.05; p = 0.7820). FP was superior to AZE in alleviating rhinorrhea (-1.15 versus -0.87; p = 0.0433), but AZE showed comparable efficacy for all other nasal and ocular symptoms. There was no clinically or statistically significant difference between AZE (-1.17) and FP (-1.43) for reduction in the overall rhinitis quality of life questionnaire score (although FP, but not AZE, significantly differed from placebo). A similar proportion of patients in the AZE and FP groups achieved a 50% reduction in rTNSS. However, more AZE patients (53.0%) exhibited a 50% reduction in rTOSS by day 14 versus FP (39.6%), and ≤3 days faster (p = 0.028). Intranasal AZE (137 micrograms/spray) and intranasal FP (50 micrograms/spray), both 1 spray/nostril b.i.d., had comparable efficacy in symptom control in moderate-to-severe SAR.

MP29-02 (a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate) in the treatment of seasonal allergic rhinitis: A randomized, double-blind, placebo-controlled trial of efficacy and safety

Many patients with allergic rhinitis (AR) have uncontrolled symptoms despite available treatment options. This study was designed to evaluate the efficacy and safety of MP29-02 (a novel intranasal formulation of fluticasone propionate [FP] and azelastine [AZ] hydrochloride), compared with monotherapy with FP, AZ, and placebo sprays for the treatment of seasonal allergic rhinitis (SAR). This 2-week randomized, double-blind, placebo-controlled trial was conducted in 779 patients with moderate-to-severe SAR. Treatments were administered 1 spray/nostril twice daily in the same vehicle and delivery device. Daily doses of AZ and FP were 548 and 200 micrograms, respectively. The primary efficacy variable was the 12-hour reflective total nasal symptom score (rTNSS), consisting of nasal congestion, sneezing, itchy nose, and runny nose. Secondary efficacy variables were (1) 12-hour reflective individual nasal symptom scores; (2) onset of action; (3) 12-hour reflective total ocular symptom score (rTOSS), including itchy eyes, watery eyes, and red eyes; and (4) the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) overall score. MP29-02 significantly reduced the mean rTNSS from baseline by -5.54 points compared with FP (-4.55; p = 0.038), AZ (-4.54; p = 0.032), and placebo (-3.03; p < 0.001), improving the rTNSS by 39% beyond the contribution of FP. All individual nasal symptoms contributed to the efficacy of MP29-02. Onset of action was within 30 minutes. MP29-02 significantly improved rTOSS compared with placebo, provided a clinically important improvement in the overall RQLQ score, and was well tolerated. In this study, MP29-02 provided more complete symptom relief than two widely used first-line AR treatments and was well tolerated.

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

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

Efficacy and safety of fluticasone furoate nasal spray in Chinese adult and adolescent subjects with intermittent or persistent allergic rhinitis

Fluticasone furoate nasal spray (FFNS) is a novel, enhanced-affinity intranasal corticosteroid administered for the management of allergic rhinitis (AR). Several studies have shown that FFNS at a dose of 110 μg once daily (o.p.d.) is effective in relieving nasal as well as ocular symptoms in adolescents and adults with AR. The primary objective of this study was to compare the efficacy and safety of FFNS 110 micrograms o.p.d. with matching placebo nasal spray for 2 weeks in Chinese adult and adolescent subjects with intermittent AR (IAR) or persistent AR (PAR). In this multicenter, randomized, double-blind, placebo-controlled, parallel-group study, patients (adults and adolescents aged ≥12 years with AR) received either FFNS 110 micrograms (n = 181) or placebo (n = 182) o.p.d. for 2 weeks. AR was defined according to Allergic Rhinitis and Its Impact on Asthma classification. Efficacy measures included reflective total nasal symptom score (rTNSS), rhinoscopy score, overall interference in activities of daily living (ADL) score, and reflective total ocular symptom score (rTOSS). FFNS significantly improved the mean change from baseline in daily rTNSS compared with placebo (treatment difference of -1.498, 95% confidence interval [-1.897, -1.099]; p < 0.0001). FFNS was also significantly more effective than placebo in decreasing rhinoscopy score (treatment difference of -1.3; p < 0.0001) and ADL score (treatment difference of -0.4; p < 0.0001). In patients with severe ocular symptoms, FFNS showed numerically better treatment effect in reducing daily rTOSS than placebo (treatment difference of -0.646; p = 0.0853). FFNS 110 micrograms o.p.d. was significantly more effective than placebo in improving nasal symptoms in Chinese patients with IAR and PAR. ClinicalTrials.gov registration number: NCT01231464.

Evaluation of the efficacy and safety of ciclesonide hydrofluoroalkane nasal aerosol, 80 or 160 μg once daily, for the treatment of seasonal allergic rhinitis

A hypotonic aqueous nasal spray of ciclesonide is indicated for the treatment of allergic rhinitis (AR). A new nasal aerosol formulation of ciclesonide containing a hydrofluoroalkane propellant delivered via a metered-dose inhaler (CIC-HFA) is currently in clinical development as a potential treatment for AR. To study the efficacy and safety of once-daily administration of CIC-HFA 80 or 160 μg compared with placebo in subjects 12 years and older with seasonal AR (SAR). Subjects 12 years and older with a ≥ 2-year history of SAR were randomized in a placebo-controlled, double-blind, parallel-group, multicenter study to receive CIC-HFA 80 or 160 μg or placebo once daily in the morning for 2 weeks. Changes from baseline in reflective total nasal symptom scores (rTNSSs), instantaneous TNSSs (iTNSSs), and reflective total ocular symptom scores (rTOSSs) in subjects with a baseline rTOSS of ≥ 5.00 were evaluated. Treatment-emergent adverse events were monitored throughout the study. Seven hundred seven subjects were randomized. From baseline, CIC-HFA 80 or 160 μg demonstrated 15.1% and 16.0% reductions in rTNSSs (P < .0001, 3.7% for placebo), 14.3% and 15.4% reductions in iTNSSs (P < .0001, 3.9% for placebo), and 15.7% and 15.0% reductions in rTOSSs (P < .001, 6.8% for placebo). The overall incidence of treatment-emergent adverse events was low and comparable between the CIC-HFA and placebo groups. In this study, once-daily treatment with CIC-HFA 80 or 160 μg demonstrated statistically significant improvements in nasal and ocular symptoms of SAR. Both doses of active treatment were well tolerated.