Intranasal antihistamines and corticosteroids in allergic rhinitis: A systematic review and meta-analysis.

BACKGROUND: There is insufficient systematized evidence on the effectiveness of individual intranasal medications in allergic rhinitis (AR). OBJECTIVES: We sought to perform a systematic review to compare the efficacy of individual intranasal corticosteroids and antihistamines against placebo in improving the nasal and ocular symptoms and the rhinoconjunctivitis-related quality of life of patients with perennial or seasonal AR. METHODS: The investigators searched 4 electronic bibliographic databases and 3 clinical trials databases for randomized controlled trials (1) assessing adult patients with seasonal or perennial AR and (2) comparing the use of intranasal corticosteroids or antihistamines versus placebo. Assessed outcomes included the Total Nasal Symptom Score, the Total Ocular Symptom Score, and the Rhinoconjunctivitis Quality-of-Life Questionnaire. The investigators performed random-effects meta-analyses of mean differences for each medication and outcome. The investigators assessed evidence certainty using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. RESULTS: This review included 151 primary studies, most of which assessed patients with seasonal AR and displayed unclear or high risk of bias. Both in perennial and seasonal AR, most assessed treatments were more effective than placebo. In seasonal AR, azelastine-fluticasone, fluticasone furoate, and fluticasone propionate were the medications with the highest probability of resulting in moderate or large improvements in the Total Nasal Symptom Score and Rhinoconjunctivitis Quality-of-Life Questionnaire. Azelastine-fluticasone displayed the highest probability of resulting in moderate or large improvements of Total Ocular Symptom Score. Overall, evidence certainty was considered "high" in 6 of 46 analyses, "moderate" in 23 of 46 analyses, and "low"/"very low" in 17 of 46 analyses. CONCLUSIONS: Most intranasal medications are effective in improving rhinitis symptoms and quality of life. However, there are relevant differences in the associated evidence certainty.

Efficacy and safety of intratonsillar immunotherapy for allergic rhinitis: A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: A lower adherence rate existed in patients receiving allergen-specific immunotherapy due to its lengthy period and adverse effects even though it is the only curative treatment for IgE-mediated allergies. Therefore, exploring innovative allergen-specific immunotherapy routes is necessary. OBJECTIVE: To explore the efficacy and safety of the intratonsillar injection of house dust mite (HDM) extract in patients with HDM-induced allergic rhinitis (AR). METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted. A total of 80 patients with HDM-induced AR were randomized to receive 6 intratonsillar injections with HDM extract or placebo in 3 months. The total nasal symptom score (TNSS), visual analogue scale of nasal symptoms, combined symptom and medication score, mini rhinoconjunctivitis quality of life questionnaire, and serum allergen-specific IgG4 to Dermatophagoides pteronyssinus were all monitored at baseline and 3 months, 6 months, and 12 months after the treatment was finished. The intent-to-treat and per-protocol set (PPS) are both analyzed. RESULTS: The primary end points TNSS and ΔTNSS were improved significantly at 3 months after the patients with AR finished a 3-month 6-injection intratonsillar immunotherapy compared with those in the placebo treatment in both intent-to-treat and PPS. Results of visual analogue scale, combined symptom and medication score, and mini rhinoconjunctivitis quality of life questionnaire were also improved significantly at 3 months after the treatment in PPS. However, the improvement effect of intratonsillar immunotherapy at 6 and 12 months was limited and uncertain based on the data. The increase of serum Der p IgG4 in the active group was significantly higher than that in the placebo group at 3, 6, and 12 months after the treatment was finished. Adverse events were monitored, and no systemic adverse reactions were observed. CONCLUSION: The clinical trial revealed that intratonsillar injection with HDM extract was safe and effective in patients with AR. Optimizing the protocol and allergen formulations is expected to increase and maintain the efficacy of this novel approach. TRIAL REGISTRATION: https://www.chictr.org.cn/index.html, identifier: ChiCTR-TRC-13003600.

Validated allergen exposure chamber is plausible tool for the assessment of house dust mite-triggered allergic rhinitis.

BACKGROUND: Allergen exposure chamber (AEC) is a clinical facility that allows exposure to allergenic airborne particles in controlled environment. Although AECs offer stable levels of airborne allergens, the validation of symptoms and other endpoints induced by allergen challenge is key for their recommendation as a plausible tool for the assessment of patients, especially in clinical research. This study aimed to demonstrate the reproducibility of defined clinical endpoints after AEC house dust mite (HDM) challenge under optimal conditions in patients with allergic rhinitis (AR). METHOD: HDM was distributed at different concentrations. The assessment was subjective by the patients: total nasal symptom score (TNSS), visual analog scale (VAS), and objective by the investigator: acoustic rhinometry, peak nasal inspiratory flow (PNIF), and nasal secretion weight. Safety was assessed clinically and by peak expiratory flow rate (PEFR) and forced expiratory volume in the first second (FEV1 ). RESULTS: Constant environment: temperature, humidity, and carbon dioxide (CO2 ) concentration were maintained during all challenges. The concentration of HDM on average remained stable within the targeted values: 1000, 3000, 5000, 7000 particles (p)/m3 . Most symptoms were observed at concentrations 3000 p/m3 or higher. The symptoms severity and other endpoints results were reproducible. 5000 p/m3 , and challenge duration of 120 min were found optimal. The procedure was safe with no lung function abnormalities due to challenge. CONCLUSION: HDM challenge in ALL-MED AEC offers a safe and reliable method for inducing symptoms in AR patients for the use in controlled clinical studies including allergen immunotherapy.

Sodium Chloride versus Lactose as a Carrier for House Dust Mite Allergen in Allergen Chamber Studies: A Clinical Study to Assess Noninferiority.

INTRODUCTION: In the Fraunhofer allergen challenge chamber (ACC), a standardized, universal, good manufacturing practice-conforming technology using a spray dried solution of lactose (L) and allergen extract has been established. In this study, we investigated the noninferiority of hypertonic sodium chloride (S) versus L as a carrier for house dust mite (HDM) allergen to simplify manufacturing, reduce costs, and allow for wider use. METHODS: Using a participant-blinded, sham exposure-controlled, single-arm, sequential intervention study, we challenged adults with HDM allergic rhinitis five times in the ACC. Participants were first exposed to S, L, and clean air (block 1), followed by S + HDM and L + HDM (block 2). Primary endpoints were mean total nasal symptom score (TNSS) and mean nasal secretion weight. RESULTS: 19 participants were enrolled in the study (10 females; mean age 32 years [22-49], 4 with mild allergic asthma). The safety profile of S + HDM and L + HDM was similar; eight participants experienced mild procedure-related adverse events including tiredness, cough, and dyspnea. Due to dropouts, 13 participants completed the study and were evaluated. Mean TNSS and nasal secretion were as follows: S 0.98, 0.28 g; L 1.1, 0.20 g; clean air 1.1, 0.23 g; S + HDM 5.7, 4.8 g; L + HDM 5.1, 5.1 g. Separate block 1/block 2 MANOVAs with TNSS and nasal secretion as dependent variables revealed no significant differences between the carriers, neither alone and compared with clean air (p = 0.2059, Wilk's λ = 0.78) nor combined with HDM (p = 0.3474, Wilk's λ = 0.89). Noninferiority of S was established using a meta-analysis-based minimal clinical important difference of -0.55: mean TNSS difference between S + HDM and L + HDM was 0.62 (90% CI: -0.51 to 1.74). CONCLUSION: S as an HDM carrier was safe and well tolerated. It was noninferior to L which makes it an adequate and easy-to-use carrier substitute.

House dust mite sublingual immunotherapy tablet safety in adolescents with allergic rhinoconjunctivitis: Worldwide clinical trial results.

BACKGROUND: The house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet is a treatment option for allergic rhinitis with/without conjunctivitis (AR/C) approved in adults worldwide and in adolescents in some countries. OBJECTIVE: To supplement existing adolescent HDM SLIT-tablet safety data by conducting the MT-18 trial in adolescents. METHODS: MT-18 (EudraCT:2020-000446-34) was a phase 3, open-label, single-arm, 28-day safety trial of daily HDM SLIT-tablet (12 SQ-HDM dose) in European adolescents (12-17 years) with HDM AR/C, with or without asthma. The primary end point was at least 1 treatment-emergent adverse event (TEAE). MT-18 results were compared with 12 SQ-HDM adolescent subpopulation data from previously described 1-year phase 3 trials conducted in North America (P001; clinicaltrials.gov:NCT01700192) or Japan (TO-203-3-2; JapicCTI:121848). RESULTS: No treatment-related anaphylaxis, epinephrine administrations, severe local swellings, severe mouth or throat edema, or eosinophilic esophagitis occurred in the trials. For MT-18 (N = 253), P001 (N adolescents = 189), and TO-203-3-2 (N adolescents = 206), the percentage of adolescents treated with 12 SQ-HDM reporting any TEAE was 88%, 95%, and 93%, respectively, and the percentage reporting any treatment-related AE (TRAE) was 86%, 93%, and 66%, respectively. The most common TRAEs were local application site reactions. Most TRAEs were mild in intensity and were typically experienced the first 1 to 2 days of treatment. There were no asthma-related TEAEs with the HDM SLIT-tablet. The safety profile appears similar between adolescents with or without asthma at baseline. CONCLUSION: The HDM SLIT-tablet was well tolerated in European, North American, and Japanese adolescents with HDM AR/C, indicating safety of the HDM SLIT-tablet is insensitive to age or geographic region. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: (P001: NCT01700192); EudraCT: (MT-18; 2020-000446-34); JapicCTI: (TO-203-3-2; 121848).

Clinical effectiveness of fluticasone furoate nasal spray for perennial allergic rhinitis in children: a comprehensive review.

OBJECTIVE: To assess the clinical effectiveness of fluticasone furoate nasal spray (FFNS) versus placebo on nasal symptoms and safety in children with perennial allergic rhinitis (AR). METHODS: A comprehensive review was conducted with data obtained from Medline and Embase databases up to April 2023. The population of interest was patients aged 2-12 years with perennial AR. The selection was limited to randomized controlled trials (RCTs), comparing FFNS with placebo. Outcomes of interest included the reflective total nasal symptoms scores (rTNSS) and safety. To assess the minimal clinically important difference for rTNSS, the Cohen's guideline was used. If the pooled standardized mean difference (SMD) and the lower limit of the 95 percent confidence interval (CI) exceeded the threshold of -0.20, effects were considered clinically significant. RESULTS: Three RCTs (959 pediatric patients) were selected. One study evaluated the short-term use of FFNS, another evaluated the long-term use of FFNS, and another evaluated both the short-term and long-term use of FFNS. FFNS produced a statistically significant reduction over placebo in rTNSS (SMD -0.18; 95 percent CI -0.35 to -0.01, p = 0.03) in long-term treatment studies, but not in short-term treatment studies. However, since the mean reduction did not reach the minimum clinically important difference (SMD -0.20), these results were considered clinically not relevant. Safety outcomes with FFNS were similar to placebo. CONCLUSIONS: The currently available evidence suggests that FFNS, 110 µg once daily, compared to placebo, does not produce a meaningful clinical effect on nasal symptom in children with perennial AR.

Triamcinolone Acetonide in the Treatment of Perennial Allergic Rhinitis: A post hoc Analysis of Quality of Life during a Phase III Study.

INTRODUCTION: Allergic rhinitis (AR) is a disease that affects ≤24% of people in Russia, significantly impairing quality of life (QoL). Intranasal corticosteroids, such as triamcinolone acetonide (TAA), are considered effective drugs for treatment. A post hoc analysis of data (phase III NASANIF trial) examined weekly QoL changes in patients receiving TAA for the treatment of perennial AR (PAR). METHODS: NASANIF (NCT03317015) was a double-blind, parallel group, multicenter, prospective, noninferiority, phase III clinical trial. Patients with PAR were randomized (1:1) to receive TAA or fluticasone propionate (FP) for 4 weeks. Here, a post hoc analysis measures QoL using a shortened Rhinoconjunctivitis Quality of Life Questionnaire (miniRQLQ). Differences in miniRQLQ score were evaluated using a mixed linear model and descriptive statistics. A subgroup analysis was performed in patients with a previous diagnosis of allergic conjunctivitis. RESULTS: Of 260 patients eligible for randomization, 128 each completed treatment with TAA or FP. Overall and individual domain scores progressively improved and were significantly different versus baseline at week 4 in both treatment groups: LS mean difference TAA: -30.92 (95% CI [-33.01 to -28.83]), p < 0.001, and FP: -31.13 (-33.23 to -29.04), p < 0.001. In both arms of the subgroup, there was a significant reduction in eye symptoms. There was no significant difference between the TAA and FP treatment groups in any analyses. CONCLUSIONS: TAA is effective in improving overall and individual domains of QoL in patients with PAR, over 4 weeks. Patients with a previous diagnosis of allergic conjunctivitis experienced significant improvements in QoL related to the resolution of these symptoms.

Triamcinolone Acetonide in the Treatment of Perennial Allergic Rhinitis: A post hoc Efficacy Analysis of a Phase III Study Performed in Russia.

INTRODUCTION: Allergic rhinitis (AR) is a disease which affects >24% of the population in Russia. Triamcinolone acetonide (TAA) is a corticosteroid used for treating AR. This post hoc analysis assesses the efficacy of intranasal TAA in improving perennial AR (PAR) symptom scores over 4 weeks. METHODS: NASANIF (NCT03317015) was a double-blind, parallel-group, multicenter, prospective, non-inferiority, phase III clinical trial in which patients with PAR were randomized (1:1) to receive TAA or fluticasone propionate (FP) over 4 weeks. Our post hoc analysis evaluates weekly change in PAR symptoms using the reflective Total Nasal Symptom Score (rTNSS), overall and for individual symptoms (sneezing, nasal itching, rhinorrhoea, and nasal obstruction). Proportion of patients and time to achieve a ≥50 or ≥75% reduction in rTNSS were assessed. For rTNSS endpoints, a linear mixed-model methodology was used; for time-to-event endpoints, cumulative incidence functions were estimated using the Kaplan-Meier method, in the per-protocol population. RESULTS: Of 260 patients, 128 each completed the study and were randomized to receive TAA or FP. From baseline to week 4, the changes in total rTNSS were -7.78 (95% CI: -8.1701 to -7.3967; p < 0.001) and -7.52 (-7.9053 to -7.1320; p < 0.001) for TAA and FP, respectively. Individual symptoms improved significantly from baseline. The proportion of patients achieving ≥50 and ≥75% reductions in total rTNSS was 88.0 and 67.2%, respectively in the TAA group. No significant differences were observed between the TAA and FP in any analyses. CONCLUSIONS: TAA produced effective and prolonged improvement of PAR symptoms over a 4-week treatment period.

Changes in olfaction & quality of life following standard medical therapy in patients with intermittent & persistent allergic rhinitis.

Background & objectives: Allergic rhinitis (AR) is an inflammatory disease prevalent worldwide which can affect both olfaction and quality of life (QoL). The objective of the present study was to assess olfaction and QoL changes in patients with AR before and after medical therapy. Methods: Adult participants (>18 yr) with AR were recruited for this study. These patients prospectively underwent olfaction testing using the modified Connecticut Chemosensory Clinical Research Centre Test and QoL assessment using Rhinoconjunctivitis QoL Questionnaire (RQLQ) before and after standard medical therapy with topical steroids and/antihistaminics. Results: Of the 150 patients recruited, 72 per cent had intermittent AR. The symptom of hyposmia was present in 34 patients (22.7%) and was more prevalent in patients with moderate-to-severe type of AR (P<0.001). However, olfaction testing revealed hyposmia/anosmia in 44 patients (29.3%). Mean composite olfaction scores were significantly higher in patients with mild AR compared to moderate/severe AR (P=0.026). The pre-therapy mean composite olfaction score in the 34 patients with olfaction disturbances was 3.1 standard deviation (±1.06 SD). Following therapy, the mean composite olfaction score rose to 4.3 (±1.34 SD) and this change was found to be significant (P<0.001). Mean pre-therapy RQLQ scores were 2.87 (0.06-5.33) overall. Significant improvement was also found in RQLQ scores following therapy (P<0.001). Mean RQLQ scores were significantly lower in those with moderate-to-severe AR (P<0.001) as well as those with intermittent AR (P=0.004). Nine patients had persistently high RQLQ scores after medical therapy. Interpretation & conclusions: Both olfaction and QoL showed significant improvement after medical therapy in Indian adults with AR. In those patients who do not improve, other causes must be sought for the persistent symptoms.

Intranasal Steroid Use and Satisfaction in Allergic Rhinitis: A Cross-Sectional Study from an Asian Perspective.

BACKGROUND: Intranasal steroid (INS) is the most effective medication class for controlling allergic rhinitis (AR) symptoms; however, its effectiveness is limited by patient compliance. Previous studies have explored INS use, compliance, satisfaction, and experience. There is, however, no Asian study on these factors in entirety. OBJECTIVE: We aimed to investigate the rate of compliance to usage of INS and explore the reasons for noncompliance in our local population. METHODS: We conducted a prospective cross-sectional study on 65 AR patients in a tertiary hospital. Recruited patients were administered a questionnaire to collect data about symptoms, INS use, and concerns they may have. Statistical analysis was performed using SPSS. RESULTS: The overall compliance rate to INS was 63.1%. Noncompliance was associated with increased frequency of dosing (p = 0.050), presence of sensory attributes (p = 0.041), and forgetfulness (p = 0.049). The top 3 most frequent sensory attributes experienced by patients include throat rundown (29.2%), aftertaste (21.5%), and immediate taste (20.0%). There was a significant difference between brands of INS with regard to sensory attributes experienced (p = 0.003) but no side effects (p = 0.070). CONCLUSIONS: Identifying risk factors for noncompliance to INS can help health-care providers address difficulties faced by patients and hence increase compliance, allowing better control of AR symptoms.

Effect of the Use of Intranasal Spray of Essential Oils in Patients with Perennial Allergic Rhinitis: A Prospective Study.

INTRODUCTION: Among allergic rhinitis (AR) symptoms, nasal obstruction particularly affects the quality of life. Antihistamines and intranasal corticosteroids are the most frequently prescribed symptomatic drugs, but their efficacy is often incomplete. Essential oils (EO) have shown an anti-inflammatory effect and potential in treating patients with AR. The aim of this study was to evaluate the effectiveness of a hypertonic EO-based nasal spray on perennial AR (PAR) symptoms. METHODS: This prospective, open-label, non-randomized, multicentric trial included 43 patients with PAR sensitized to mites, not controlled for more than a year. All were treated with Puressentiel® Respiratory-Decongestant Nasal Spray for 30 days. Their usual treatment remained unchanged during the study period. Before and after treatment, each participant filled out a rhinitis questionnaire, the Allergic Rhinitis Control Test (ARCT). A nasal inspiratory peak flow (NIPF) was performed. RESULTS: The mean ARCT was 16.4 and 20.5 at D0 and D30, respectively (p < 0.001); the mean increase between D0 and D30 was 4.1 (p < 0.001). The proportion of patients with controlled rhinitis after 30 days of treatment was 69.8 versus 14% before treatment (p < 0.001). The mean NIPF was 86.5 L/min and 105.1 L/min at D0 and D30, respectively (p < 0.001); the mean increase between D0 and D30 was 18.5 L/min. CONCLUSION: A hypertonic EO-based nasal spray could be a new and natural option in the management of PAR. It could also be used as an add-on therapy when nasal symptoms are not fully controlled.

Efficacy of dupilumab on clinical outcomes in patients with asthma and perennial allergic rhinitis.

BACKGROUND: Comorbid perennial allergic rhinitis (PAR) or year-round aeroallergen sensitivity substantially contributes to disease burden in patients with asthma. Dupilumab blocks the shared receptor for interleukin (IL) 4 and IL-13, key drivers of type 2 inflammation that play important roles in asthma and PAR. In the LIBERTY ASTHMA QUEST trial (NCT02414854), dupilumab reduced severe asthma exacerbations and improved forced expiratory volume in 1 second (FEV1) in patients with uncontrolled, moderate-to-severe asthma, with greater efficacy observed in patients with elevated type 2 inflammatory biomarkers at baseline (blood eosinophils and fractional exhaled nitric oxide). OBJECTIVE: To assess dupilumab efficacy in LIBERTY ASTHMA QUEST patients with comorbid PAR. METHODS: Severe asthma exacerbation rates, FEV1, asthma control (5-item Asthma Control Questionnaire), rhinoconjunctivitis-specific health-related quality of life (Standardized Rhinoconjunctivitis Quality of Life Questionnaire +12 scores), and type 2 inflammatory biomarkers during the 52-week treatment period were assessed. RESULTS: A total of 814 of the 1902 patients (42.8%) had comorbid PAR (defined as an allergic rhinitis history and ≥1 perennial aeroallergen specific immunoglobulin E (IgE) level ≥0.35 kU/L at baseline). Dupilumab, 200 and 300 mg every 2 weeks, vs placebo reduced severe exacerbations rates by 32.2% and 34.6% (P < .05 for both) and improved FEV1 at week 12 by 0.14 L and 0.18 L (P < .01 for both); greater efficacy was observed in patients with elevated baseline blood eosinophil counts (≥300 cells/µL) and fractional exhaled nitric oxide. Dupilumab treatment also numerically improved the 5-item Asthma Control Questionnaire and Standardized Rhinoconjunctivitis Quality of Life Questionnaire +12 scores and suppressed type 2 inflammatory biomarkers. CONCLUSION: Dupilumab improved key asthma-related outcomes, asthma control, and rhinoconjunctivitis-specific health-related quality of life while suppressing type 2 inflammatory biomarkers and perennial allergen-specific IgE in patients with moderate-to-severe asthma and comorbid PAR, highlighting its dual inhibitory effects on IL-4 and IL-13 and its role in managing asthma and PAR.

Triamcinolone Acetonide versus Fluticasone Propionate in the Treatment of Perennial Allergic Rhinitis: A Randomized, Parallel-Group Trial.

BACKGROUND: Intranasal sprays are recommended as targeted therapy for allergic rhinitis (AR). Triamcinolone acetonide is a nasal corticosteroid preparation indicated for the treatment of seasonal and perennial AR (PAR) in different countries worldwide. OBJECTIVES: In order to determine the efficacy of triamcinolone acetonide in the treatment of PAR, the non-inferiority of triamcinolone acetonide to fluticasone propionate was assessed in Russian adults. METHODS: In this randomized, double-blind, parallel-group, multicenter, prospective, non-inferiority, phase III clinical trial, a total of 260 patients with persistent PAR were randomized to receive either triamcinolone acetonide or fluticasone propionate nasal sprays for 4 weeks. The efficacy in symptom control was evaluated using the reflective total nasal symptom score (rTNSS) from baseline (day 0) to day 28. Safety was assessed through the reporting of adverse events. RESULTS: The rTNSS mean values decreased from baseline to the end of study treatment (day 28) in both groups: -8.2 ± 3.0 in the triamcinolone acetonide arm versus -8.0 ± 2.8 in the fluticasone propionate arm. The mean difference between the groups (triamcinolone acetonide - fluticasone propionate) for rTNSS change from baseline was -0.2 (95% confidence interval -0.89 to 0.54), with an upper confidence limit of 0.54, which is lower than the non-inferiority margin of 0.8. Triamcinolone acetonide was well tolerated, with no difference in adverse event occurrence compared with fluticasone propionate. CONCLUSIONS: Triamcinolone acetonide proved to be non-inferior to fluticasone propionate in adult patients with PAR; both treatments decreased rTNSS values and showed a good safety profile.

Long-term safety and efficacy of olopatadine-mometasone combination nasal spray in patients with perennial allergic rhinitis.

Background: Safety and efficacy of GSP301 nasal spray, an investigational fixed-dose combination of olopatadine hydrochloride and mometasone furoate, was established in three large, 2-week seasonal allergic rhinitis studies. Objective: To evaluate long-term (52 weeks) safety and efficacy of GSP301 in patients with perennial allergic rhinitis (PAR). Methods: In this randomized, double-blind, parallel-group study, 601 patients (ages ≥ 12 years) with PAR were randomized 4:1:1 to twice-daily GSP301 (olopatadine 665 µg and mometasone 25 µg [pH 3.7]) or two GSP301 vehicle formulations (placebo pH 3.7 or 7.0). Safety (primary end point) was monitored through adverse events (AE), laboratory assessments, vital signs, and physical examinations at weeks 30 and 52. The change from baseline in the average A.M. reflective Total Nasal Symptom Score (rTNSS) and instantaneous Total Nasal Symptom Score (iTNSS), Physician-assessed Nasal Symptom Scores (PNSS), and quality of life were assessed for GSP301 versus placebo pH 3.7 (p < 0.05 was considered statistically significant). Results: At week 52, treatment-emergent AEs (TEAE) occurred in 51.7, 41.4, and 53.5% of patients in the GSP301, placebo pH 3.7 and placebo 7.0 groups, respectively. No clinically meaningful differences were observed in TEAE incidences or other safety assessments across treatments. At weeks 6 and 30, GSP301 provided significant and clinically meaningful improvements in average rTNSS and iTNSS versus placebo pH 3.7 (p < 0.01, all comparisons). Similarly, at week 52, GSP301 provided significant and clinically meaningful improvements in rTNSS (least-squares mean difference -0.91 [95% confidence interval {CI}, -1.35 to -0.47]; p < 0.001), and iTNSS (least-squares mean difference -0.75 [95% CI, -1.17 to -0.33]; p < 0.001) versus placebo pH 3.7, with significant improvements in each individual symptom (p < 0.05, all comparisons). PNSS and quality of life were significantly improved versus placebo pH 3.7 at weeks 6 and 30 (p < 0.05, all comparisons), but these greater improvements did not reach statistical significance at week 52 (PNSS, p = 0.552; quality of life, p = 0.790). Conclusion: Twice-daily GSP301 was well tolerated and provided statistically significant and clinically meaningful improvements in PAR nasal symptoms versus placebo over 52 weeks and demonstrated a favorable safety profile and efficacy.Clinical trial NCT02709538, www.clinicaltrials.gov.

Efficacy and safety of dupilumab in perennial allergic rhinitis and comorbid asthma.

BACKGROUND: Dupilumab, an anti-IL-4 receptor α mAb, inhibits IL-4/IL-13 signaling, key drivers of type 2/TH2 immune diseases (eg, atopic/allergic disease). In a pivotal, phase 2b study (NCT01854047), dupilumab reduced severe exacerbations, improved lung function and quality of life, and was generally well tolerated in patients with uncontrolled persistent asthma despite using medium-to-high-dose inhaled corticosteroids plus long-acting ß2-agonists. OBJECTIVE: To examine dupilumab's effect on the 22-item Sino-Nasal Outcome Test (SNOT-22) total score and its allergic rhinitis (AR)-associated items in asthma patients with comorbid perennial allergic rhinitis (PAR). METHODS: A post hoc analysis reporting data from the phase 2b study for the 200 and 300 mg every 2 week (q2w) doses under investigation in phase 3 (NCT02414854) was carried out. PAR was defined at study entry as a specific response to typical perennial antigens (IgE ≥0.35 Ku/L). RESULTS: Overall, 241 (61%) patients had PAR. In asthma patients with PAR, dupilumab 300 mg q2w versus placebo significantly improved SNOT-22 total score (least squares mean difference, -5.98; 95% CI, -10.45 to -1.51; P = .009) and all 4 AR-associated symptoms evaluated (nasal blockage, -0.60; 95% CI, -0.96 to -0.25; runny nose, -0.67; 95% CI, -1.04 to -0.31; sneezing, -0.55; 95% CI, -0.89 to -0.21; postnasal discharge, -0.49; 95% CI, -0.83 to -0.16; all P < .01). Dupilumab 200 mg q2w demonstrated numerical, but not statistically significant, decreases in SNOT-22 total score (-1.82; 95% CI, -6.46 to 2.83; P = .443 vs placebo) and in each AR-associated symptom. In patients without PAR, no differences were observed for these measures versus placebo. CONCLUSIONS: Dupilumab 300 mg q2w significantly improved AR-associated nasal symptoms in patients with uncontrolled persistent asthma and comorbid PAR.

The burden of allergic rhinitis and allergic rhinoconjunctivitis on adolescents: A literature review.

OBJECTIVE: To evaluate the literature regarding the burden of allergic rhinitis (AR) and allergic rhinoconjunctivitis (ARC) in adolescents (aged 10-19 years). DATA SOURCES: Searches were performed in MEDLINE, Embase, Health Technology Assessment Database, and National Health Service Economic Evaluation Database for studies that evaluated concepts of symptoms, quality of life (QOL), daily activities, sleep, examination performance, school absenteeism and presenteeism, and treatment burden in adolescents with AR or ARC. STUDY SELECTIONS: English-language journal articles indexed in the last 15 years describing noninterventional, population-based studies. Records were assessed by 2 independent reviewers. RESULTS: A total of 27 articles were identified; outcomes evaluated were symptoms (n = 6 studies), QOL (n = 9), daily activities (n = 5), emotional aspects (n = 3), sleep (n = 6), education (n = 7), and treatment burden (n = 2). AR symptoms rated most bothersome were rhinorrhea, nasal congestion, and itchy eyes. QOL was worse in adolescents with AR vs controls regardless of QOL instrument used. Nasal symptoms and nasal obstruction were more likely to be associated with poor QOL in adolescents than in adults or younger children, respectively. Daily functioning and sleep were also negatively affected by AR. In addition, a detrimental effect on absenteeism, school productivity, and academic performance was reported. CONCLUSION: Although AR and ARC are sometimes perceived as trivial conditions, this review indicates that their effect on adolescent life is negative and far-reaching. It is critical that clinicians gain a greater understanding of the unique burden of AR and ARC in adolescents to ensure they receive prompt and appropriate care and treatment to improve clinical and academic outcomes.

Comparative Effect of Beclomethasone Dipropionate and Cetirizine on Acoustic Rhinometry Parameters in Children With Perennial Allergic Rhinitis: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: The effect of intranasal corticosteroids and oral antihistamines on acoustic rhinometry parameters has not been directly compared. The primary objective was to compare the effect of a 21-day course of treatment with nasal beclomethasone dipropionate (nBDP) with that of cetirizine (CTZ) on nasal patency measured using acoustic rhinometry in children with perennial allergic rhinitis (PAR). The secondary objective was to compare the effect of both drugs on nasal cytology, symptom severity, sleep quality, and quality of life. METHODS: In this 21-day, open-label, randomized controlled study, 34 children with PAR (age 6-14 years) with a Total 5-Symptom Score (T5SS) ≥5 received nBDP 100 µg per nostril twice daily or CTZ 10 mg tablets once daily. The measures of effect were the least square mean change (LSmc) in nasal volume, minimal cross-sectional area (MCA), and nasal cytology, as well as the scores on the T5SS, Pittsburgh Sleep Quality Index (PSQI), and Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ). RESULTS: After 21 days, nBDP improved nasal volume and MCA more than CTZ (LSmc, 2.21 cm3 vs 0.20 cm3 [P=.013]; and LSmc 0.63 cm2 vs 0.13 cm2 [P=.002], respectively). Compared with the CTZ group, a more marked improvement was found in the nBDP group with respect to eosinophil classes (LSmc, -1.10 vs -0.40; P=.031) and neutrophil classes (LSmc, -0.97 vs -0.17; P=.010), T5SS (LSmc, -5.63 vs -3.54; P=.008), PSQI (LSmc, -1.30 vs -0.19; P=.025), and PRQLQ total scores (LSmc, -1.15 vs -0.69; P=.031). CONCLUSIONS: In children with PAR, nBDP is more effective than CTZ in improving nasal patency measured by acoustic rhinometry, with associated beneficial effects on nasal cytology, symptoms, sleep quality, and quality of life.

Costs of perennial allergic rhinitis and allergic asthma increase with severity and poor disease control.

BACKGROUND: Perennial allergic rhinitis (PAR) represents a global and public health problem, due to its prevalence, morbidity, and impact on the quality of life. PAR is frequently associated with allergic asthma (AA). Costs of PAR with or without AA are poorly documented. OBJECTIVE: Our study aimed to detail medical resource utilization (MRU) and related direct cost for PAR, with or without concomitant AA, in France. METHODS: Using Electronic Health Records (EHRs), we identified in 2010 two cohorts of PAR patients, based on General Practitioners' diagnoses and prescribing data, with and without concomitant AA. For each patient, the EHRs were linked to corresponding claims data with MRU and costs during years 2011 to 2013. Predefined subgroup analyses were performed according to severity of PAR and level of AA control. RESULTS: The median annual cost reimbursed by social security system for a patient with PAR, and no AA was 159€ in 2013. This varied from 111€ to 188€ depending on PAR severity. For patients with PAR and concomitant AA, the median annual cost varied between 266€ and 375€, and drug treatment accounted for 42-55% of the costs, depending on asthma control. CONCLUSION: This study linking diagnoses from EHRs to claims data collected valid information on PAR management, with or without concomitant AA, and on related costs. There was a clear increase in costs with severity of PAR and control of AA.

Symptomatic treatment of pollen-related allergic rhinoconjunctivitis in children: randomized controlled trial.

BACKGROUND: About 12% of children are affected by allergic rhinoconjunctivitis (AR). Although the main symptomatic treatments are intranasal corticosteroids (INCS) (daily or on demand) and oral antihistamines, it remains unclear which treatment provides the best relief of symptoms. Therefore, this study examines whether daily use of INCS is superior to on-demand use or to oral antihistamines on demand. METHODS: A single-blinded randomized controlled trial in children (aged 6-18 years) with pollen-related AR. Patients received either INCS daily (fluticasone propionate), INCS on demand (fluticasone propionate) or oral antihistamine on demand (levocetirizine) for 3 months during the grass pollen season. A daily online symptom diary on both nose and eye symptoms was completed. The primary outcome was the percentage of symptom-free days. RESULTS: A total of 150 children were randomized. The percentage symptom-free days was in favour of INCS on demand (30%) compared with INCS daily (22%), that is 8% difference (95% CI -5 to +21%; not significant). The antihistamine on-demand group had 15% symptom-free days, that is 7% difference compared to INCS daily (95% CI -6 to +19%;, not significant). Patients in the INCS on-demand group used on average 61% less fluticasone than patients in the INCS daily group during the study period (P < 0.0001). CONCLUSIONS: This trial with three parallel treatment groups shows that INCS daily was not superior to INCS on demand or to antihistamine on demand regarding the number of symptom-free days. An on-demand INCS strategy has the advantage of a lower overall corticosteroid exposure and less costs.

Nasal obstructive disorders impair health-related quality of life in adolescents with persistent allergic rhinitis: A real-life study.

BACKGROUND: We previously reported a higher prevalence of nasal obstructive disorders (NOD) in pediatric patients with persistent allergic rhinitis (PER) not responding to medical treatment. The aim of this study was to determine the impact of NOD on quality of life (QoL) in this population. METHODS: Real-life prospective study including 142 patients (41 children, 6-11 years old and 101 adolescents, 12-17 years old) with moderate and severe PER. After 2 months of medical treatment (intranasal steroids and antihistamines), patients were asked whether their symptoms had improved (yes/no) and classified accordingly in R, responders and NR, non-responders. Nasal symptoms (visual analog scale, VAS), NOD (nasal endoscopy), and QoL (PRQLQ, AdolQRLQ) were also assessed. RESULTS: Sixty-nine adolescents and 24 children were included in the NR group. NR presented worse QoL overall scores in adolescents (3.16±1.1 vs 1.63±0.99; P=.00001) and children (2.19±0.82 vs 1.51±0.77, P=.02). Medical treatment failure was associated with worse outcomes in QoL (adolescents OR: 1.6, P<.0001; children OR: 1.04, P=.036). Female adolescents presented worse QoL scores than males (3.19 vs 2.36, P=.001). The presence of obstructive septal deviation (OR: 1.02, P=.005), obstructive turbinate hyperplasia (OR: 1.03, P=.0006), and coexistence of both (OR=2.06, P=.001) was associated with worse QoL in adolescents. A strong and highly significant correlation was found between nasal symptoms VAS and QoL. CONCLUSION: The presence of NOD, particularly in adolescents, is associated with poor QoL outcomes. Assessment of NOD in pediatric PER should be considered an essential approach to determine the response to treatment and its impact on patient's QoL.