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Study objective Acute urticaria is a frequent presentation in emergency departments (EDs), urgent care centers, and other clinical arenas. Treatment options are limited if diphenhydramine is the only intravenous antihistamine offered because of its short duration of action and well-known adverse effects. We evaluate cetirizine injection, the first second-generation injectable antihistamine, for acute urticaria in this multicenter, randomized, noninferiority, phase 3 clinical trial. Methods Adult patients presenting to EDs and urgent care centers with acute urticaria requiring an intravenous antihistamine were randomized to either intravenous cetirizine 10 mg or intravenous diphenhydramine 50 mg. The primary endpoint was the 2-hour pruritus score change from baseline, with time spent in treatment center and rate of return to treatment centers as key secondary endpoints. Frequency of sedation and anticholinergic adverse effects were also recorded. Results Among 262 enrolled patients, the 2-hour pruritus score change from baseline for intravenous cetirizine was statistically noninferior to that for intravenous diphenhydramine (–1.6 versus –1.5; 95% confidence interval –0.1 to 0.3), and in favor of cetirizine. Treatment differences also favored cetirizine for mean time spent in treatment center (1.7 versus 2.1 hours; P=.005), return to treatment center (5.5% versus 14.1%; P=.02), lower change from baseline sedation score at 2 hours (0.1 versus 0.5; P=.03), and adverse event rate (3.9% versus 13.3%). Conclusion Intravenous cetirizine is an effective alternative to intravenous diphenhydramine for treating acute urticaria, with benefits of less sedation, fewer adverse events, shorter time spent in treatment center, and lower rates of revisit to treatment center.

Background: Allergic rhinitis (AR) is the most common chronic noncommunicable disease worldwide that affects any age during the human life span but raises particular concerns among the parents and caregivers of the children who are affected. H1-receptor antagonists and corticosteroids provide the most effective way of bringing the condition under control. Intranasal application of these medications has the advantage of a faster onset of action and avoids systemic unwanted adverse effects. The only combination treatment, which comprises azelastine hydrochloride and fluticasone propionate, so far in a single advanced delivery system has proven its efficacy and safety in clinical trials of adult patients with AR. Objective: To critically review and identify gaps in the existing data for children in all different strata of pediatric ages. Methods: We searched the specialized medical literature for publications on the efficacy and safety of the combined formulation of azelastine and fluticasone in a single delivery device in adolescents (ages < 18 years) and children (ages < 12 years). Results: Altogether, 12 peer-reviewed articles have been published about trials that also involved subjects in different strata of the pediatric ages, seven of the articles pooled adolescents and adults. Three articles presented the results of studies in children ages 4 to 11 years specifically designed to overcome the difficulties that children experience in expressing themselves verbally. Conclusion: All the trials with the novel combination product that involved young children and adolescents documented its efficacy, effectiveness, and safety. However, the numbers of the youngest children (ages 4 and 5 years) were low, which suggested that further data about safety and efficacy in this age group are needed.

Background Treatment options for peanut allergy are limited. In previous clinical trials, epicutaneous immunotherapy with a patch containing 250-μg peanut protein (Viaskin™ Peanut 250 μg [VP250]) was well tolerated and statistically superior to placebo in desensitizing peanut-allergic children. Objective To examine the safety of VP250 in children, using a study design approximating potential real-world use. Methods REALISE is a phase 3 multicenter study consisting of a 6-month, randomized, double-blind, placebo-controlled period followed by open-label active treatment. Children aged 4 to 11 years with physician diagnosis of peanut allergy received daily treatment with placebo (6 months) or VP250 (up to 36 months). Data from the 6-month, randomized, controlled phase of REALISE are reported. Results Three hundred ninety-three children were randomized 3:1 to receive VP250 (n=294) or placebo (n=99) for 6 months; 284 (72.3%) children had a history of peanut anaphylaxis. According to parent diary, all participants receiving VP250 and 83.8% receiving placebo reported at least 1 episode of local skin reaction, with frequency decreasing over time. Only 4 participants (1.4%) receiving VP250 discontinued due to adverse events. Epinephrine was administered for allergic reactions attributed to VP250 in 7 children (2.4%), of whom 5 remained in the study; none involved severe anaphylaxis. Overall adverse event rates were similar among participants with and without history of peanut anaphylaxis. Conclusions In a study designed to mirror real-world use, VP250 was observed to be well tolerated in peanut-allergic children, consistent with previous phase 2b and 3 studies.

Allergic rhinitis (AR) is prevalent, and many patients present with moderate-to-severe symptomatic disease. The majority of patients are not satisfied with their AR treatment, despite the use of concurrent medications. These gaps underscore the need for treatment with more effective options for moderate-to-severe AR. The authors’ objective was to review systematically the efficacy and safety of MP-AzeFlu for the treatment of AR. The primary outcomes studied were nasal, ocular, and total symptoms. Other outcomes included time to onset and of AR control, quality of life, and safety. Searches of PubMed and Cochrane databases were conducted on May 14, 2020, with no date restrictions, to identify publications reporting data on MP-AzeFlu. Clinical studies of any phase were included. Studies were excluded if they were not in English, were review articles, did not discuss the safety and efficacy of MP-AzeFlu for AR symptoms. Treatment of AR with MP-AzeFlu results in effective, sustained relief of nasal and ocular symptoms, and faster onset and time to control compared with intranasal azelastine or fluticasone propionate. Long-term use of MP-AzeFlu was safe, with benefits in children, adults, and adults aged ≥65 years. Other treatment options, including fluticasone propionate and azelastine alone or the combination of intranasal corticosteroids and oral antihistamine, do not provide the same level of efficacy as MP-AzeFlu in terms of rapid and sustained relief of the entire AR symptom complex. Furthermore, MP-AzeFlu significantly improves patient quality of life. MP-AzeFlu is a currently available combination that may satisfy all these patient needs and expectations.

Purpose: Most patients with allergic rhinitis (AR) have moderate-to-severe disease, requiring complete and prompt relief when symptoms occur. The time course of fluticasone propionate (FP) penetration into nasal tissues after intranasal administration is not well characterized. The goal of this proof-of-concept study was to evaluate the mucosal penetration of FP from fixed-combination FP-azelastine nasal spray (MP-AzeFlu) compared with an FP-only nasal spray in an in vitro, 3-dimensional human bronchial tissue model. Materials and Methods: Absorption of FP from MP-AzeFlu and FP nasal spray was modeled using EpiAirway (TM) 606 (MatTek Corporation; Ashland, MA, USA) tissue cultured in vertical diffusion cells. The dosing amount of MP-AzeFlu was optimized in a pilot study. Based on the results of the pilot study, 10 mu L of MP-AzeFlu (3.65 mu g; n = 8) and 10 mu L of FP nasal spray (5.00 mu g; n = 8) were evaluated for penetration of tissue. Tissue integrity was monitored with Lucifer yellow. FP in the receiving media was quantified for each sample using liquid chromatography with tandem mass spectrometry. Results: MP-AzeFlu and FP nasal spray were associated with similar FP accumulation profiles in the receiving media, but the permeability of FP was greater for MP-AzeFlu during hours 0 to 6, suggesting faster absorption for MP-AzeFlu. No indications of compromised tissue integrity were found in any of the tested cells. Conclusion: The higher and more rapid penetration of FP from MP-AzeFlu supports the use of MP-AzeFlu for patients with AR, particularly when prioritizing fast and pronounced symptom relief.

The safety of a novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP) has been established in adults and adolescents with allergic rhinitis but not in children12 years old.To evaluate the safety and tolerability of an intranasal formulation of AZE and FP in children ages 4-11 years with allergic rhinitis.The study was a randomized, 3-month, parallel-group, open-label design. Qualified patients were randomized in a 3:1 ratio to AZE/FP (n = 304) or fluticasone propionate (FP) (n = 101), one spray per nostril twice daily, and to one of three age groups: ≥4 to6 years, ≥6 to9 years, and ≥9 to12 years. Safety was assessed by child- or caregiver-reported adverse events, nasal examinations, vital signs, and laboratory assessments.The incidence of treatment-related adverse events (TRAEs) was low in both the AZE/FP (16%) and FP-only (12%) groups after 90 days' continuous use. Epistaxis was the most frequently reported TRAE in both groups (AZE/FP, 9%; FP, 9%), followed by headache (AZE/FP, 3%; FP, 1%). All other TRAEs in the AZE/FP group were reported by ≤1% of the children. The majority of TRAEs were of mild intensity and resolved spontaneously. Results of nasal examinations showed an improvement over time in both groups, with no cases of mucosal ulceration or nasal septal perforation. There were no unusual or unexpected changes in laboratory parameters or vital signs.The intranasal formulation of AZE and FP was safe and well tolerated after 3 months' continuous use in children with allergic rhinitis.The study was registered onext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://ClinicalTrials.gov"ClinicalTrials.gov/ext-link(NCT01794741).

BACKGROUND Despite current guidelines, many patients with asthma remain symptomatic, particularly those intolerant of,unresponsive to, or uncontrolled by long-acting beta 2-agonists (LABAs). Tiotropium bromide, delivered through the Respimatsoft-mist inhaler in 2 puffs of 1.25 micrograms each, is approved for the long-term, maintenance treatment of asthma in patients aged greater than or equal to 6 years. OBJECTIVE An overview of the use of once-daily tiotropium Respimat 2.5 micrograms in adults and adolescents with varyingdegrees of asthma severity. The role of the parasympathetic nervous system in the pathophysiology of asthma, the developmentof tiotropium for respiratory disease, and the value of the Respimat inhaler are also discussed. METHODS A literature search of all phase II and phase III trials of once-daily tiotropium Respimat 2.5 micrograms. RESULTS Once-daily tiotropium Respimat 2.5 micrograms was studied in five phase III studies: three studies in adults andtwo in adolescents aged 12-17 years. Tiotropium Respimat 2.5 micrograms demonstrated efficacy in adults and adolescentswith mild, moderate, or severe asthma, showing significant improvements in lung function and asthma control in patients with uncontrolled asthma despite inhaled corticosteroids (ICS) or ICS plus LABA use. The adverse event profile of tiotropium was very acceptable, with safety similar to placebo. CONCLUSION Once-daily tiotropium Respimat 2.5 micrograms has positive attributes that include efficacy, a safety profilesimilar to placebo, once-daily dosing, administration by inhalation, and delivery in the easy-to-use and consistent-dosing Respimat device. However, more data are needed on the effects of tiotropium on clinical outcomes, patients' day-to-day lives, and real-world effectiveness.

Background Allergic conjunctivitis (AC), although one of the most common ocular disorders in pediatric patients, is frequently overlooked, misdiagnosed, and undertreated in children. Objective To guide pediatric health care professionals in the optimal diagnosis and management of AC in pediatric patients. Methods To identify any existing best practice guidelines for the diagnosis and treatment of AC in pediatric patients, a review of the literature published between 2004 and January 2015 was conducted. Diagnosis and treatment algorithms and guidelines for pediatric patient referrals were then developed. Results A literature search to identify best practice guidelines for the treatment of AC in pediatric patients failed to return any relevant articles, which highlighted the need for best practice recommendations. Based on publications on adult AC and clinical experience, this review provides step-by-step guidance for pediatric health care professionals, including recognizing clinical features of AC, establishing a comprehensive medical history, and performing a thorough physical examination to ensure a correct diagnosis and the optimal treatment or referral to an eye care specialist or allergist when required. In addition to established drug treatments, the role of subcutaneous and sublingual immunotherapy is discussed to inform pediatric health care professionals about alternative treatment options for patients who do not tolerate pharmacotherapy or who do not respond sufficiently. Conclusion The diagnostic and treatment algorithms and guidelines provided in this review help address the current literature and educational gap and may lead to improvements in diagnosis and management of pediatric AC.

Background 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. Methods 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. Results 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. Conclusions 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.

Purpose. In vitro evaluations using an anatomical model of the human nasal cavity quantified the distribution of azelastine HCl (AZ) and fluticasone propionate (FP) in a single nasal spray (Dymista) compared to sequential sprays of marketed azelastine (Astelin) and either Flonase or generic fluticasone. Methods. The cast was divided into 4 …

Background Intranasal sprays are recommended as targeted therapy for allergic rhinitis (AR) by providing direct delivery of medication to the nasal mucosa, reducing the potential for systemic adverse effects, decreasing burden of disease, and improving quality of life. Objective To review currently available intranasal sprays indicated for maintenance therapy of AR in the United States: intranasal antihistamines (INAH); intranasal corticosteroids (INCS); and MP-AzeFlu, a single formulation nasal spray of the INAH, azelastine hydrochloride, and the INCS, fluticasone propionate. Methods MEDLINE searches were conducted to identify placebo-controlled studies of commercially available prescription nasal sprays at U.S.-approved doses and indications, and published after an earlier systematic review of AR treatment. Inclusion criteria were ≥20 subjects; duration of ≥2 weeks for seasonal (or episodic) AR, ≥4 weeks for perennial (or persistent) AR, and reporting a total nasal symptom score as a primary or secondary outcome. Results Twenty studies met the inclusion criteria: 4 pediatric, 16 adult/adolescent. There were 4 perennial AR studies (381 children, 1607 adults) and 16 seasonal AR trials (3081 children, 6548 adults). In these studies, 2451 subjects (481 children, 1970 adults) received an INCS, 3001 (1116 children, 1885 adults) received an INAH, and 346 adult subjects received MP-AzeFlu. All active treatments were well tolerated and effective as measured by the reduction in nasal symptoms. Head-to-head comparisons were only available for MP-AzeFlu versus the individual active agent components. MP-AzeFlu provided significantly greater symptom relief than either azelastine or fluticasone propionate alone and with an onset starting at 30 minutes after the dose. Conclusion The most recent addition to intranasal sprays for the maintenance therapy of AR is MP-AzeFlu, a single formulation nasal spray of azelastine hydrochloride and fluticasone propionate in an advanced delivery system. Analysis of clinical data showed this to be the first new intranasal medication that provides greater clinical benefit than an INCS in treating AR.

Flunisolide hydrofluoroalkane (HFA) with integrated spacer is the most recent reformulated inhaled corticosteroid (ICS) for asthma available in the United States. It is the only product that combines a corticosteroid extrafine aerosol with a built-in spacer. The potential clinical benefit of the flunisolide HFA formulation and its integrated spacer for treating persistent asthma was assessed through a comprehensive review of the published literature and data from the past 10 years focusing on (1) flunisolide, the molecule, and the impact of the HFA reformulation; (2) updated information on the anti-inflammatory response to flunisolide HFA, particularly in the distal airways; and (3) the usefulness of an integrated spacer. Flunisolide HFA was found effective and safe in clinical studies and comparable with the chlorofluorocarbon (CFC) formulation, but at about one-third the dose of flunisolide CFC, likely reflecting both the device and the particle size of the reformulated product. Compared with the CFC formulation, the extrafine aerosol and smaller particle size of flunisolide HFA substantially increased pulmonary deposition and decreased oropharyngeal deposition. The integrated spacer further enhanced the pulmonary/oropharyngeal deposition ratio. Examination of lung biopsy specimens indicated a favorable anti-inflammatory response to flunisolide HFA in peripheral airways. Pediatric studies showed no significant effects on growth. The data indicate that flunisolide HFA is a safe and effective maintenance therapy for asthma patients. The integrated spacer may provide an added advantage for patients, especially those who may be more likely to experience adverse effects of ICSs, both local and systemic, including children susceptible to adverse effects on growth.

Dose-response of formoterol via pressurized metered-dose inhaler (pMDI) has not been determined in asthmatic pediatric patients aged 6 to

Background MP29-02 is a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate (FP) in an advanced delivery system for the treatment of seasonal allergic rhinitis. Objective The objective of this study was to evaluate the long-term safety of MP29-02 in subjects with chronic allergic (perennial) or nonallergic (vasomotor) rhinitis. Methods This was a 1-year, randomized, open-label, active-controlled, parallel-group study in subjects with chronic allergic or nonallergic rhinitis. A total of 612 subjects were randomized in a 2:1 ratio to (1) MP29-02, one spray per nostril twice daily (total daily doses of azelastine hydrochloride and FP were 548 mcg and 200 mcg, respectively); or (2) FP, 2 sprays per nostril once daily (total daily dose 200 mcg). Safety and tolerability assessments were made at months 1, 3, 6, 9, and 12. Results The incidence of treatment-related adverse events was low with both MP29-02 (9.4%) and FP (11.1%), with no evidence of late-occurring adverse events. Nasal examinations showed no evidence of nasal mucosal ulcerations or septal perforations with MP29-02, and the overall incidence of adverse findings was reduced as the study progressed. There were no unusual or unexpected ocular examination findings and no clinically important laboratory findings or clinically important differences between groups in fasting AM serum cortisol levels after 12 months of treatment. Conclusions MP29-02 was well tolerated. There were no safety findings that would preclude the long-term use of MP29-02 in the treatment of allergic rhinitis.

Patients' preference and satisfaction with their nasal allergy medications may be influenced by their sensory attributes. This study evaluates patient preference and satisfaction with ciclesonide hydrofluoroalkane nasal aerosol (CIC-HFA) compared with mometasone furoate aqueous nasal spray (MFNS). Symptomatic subjects with perennial allergic rhinitis (PAR) were randomized to CIC-HFA at 74 micrograms or MFNS at 200 micrograms q.d. in an open-label, two-period, crossover study. Subject preference was recorded as total preference score (TPS; average of 17 individual preference items) at the end of treatment period 2, and satisfaction was assessed with a 76-item, self-administered instrument at baseline and at the end of each 2-week treatment period. The primary assessments were TPS and regimen attributes composite satisfaction score composed of two of nine satisfaction subscales: sensory impact (including medication running out of the nose, medication running down the throat, and impact on smell and taste) and regimen management (comprised of issues relating to dosing and ability to remember to take medication). Two hundred ninety-four subjects completed the study. A total of 68.1% of subjects preferred CIC-HFA (p < 0.0001 versus MFNS), with a mean TPS of 68.3 versus 31.7 for the MFNS group. The regimen attributes composite satisfaction score significantly (p < 0.0001 for each treatment period) favored CIC-HFA versus MFNS at the end of treatment period 1 (85.5 vs 77.6) and treatment period 2 (83.0 versus 73.5), respectively. In this study, subjects reported higher preference for and satisfaction with CIC-HFA compared with MFNS, suggesting significant differences in patient perception of attributes in favor of CIC-HFA. Clinical trial registration URL and registration number: www.clinicaltrials.gov/ct2/show/NCT01401465.

Introduction Acute urticaria is the most common symptom of acute allergic reactions. Diphenhydramine injection, the only available H1-antihistamine injection, is a 1stgeneration antihistamine with many side effects including sedation, short duration, anticholinergic effect, drug-drug interactions. Cetirizine injection, the first innovation in the H1-antihistamine injection space since 1955, minimizes these problems. A phase 3 clinical trial using a newly developed IV cetirizine was compared to IV diphenhydramine in treatment of acute urticaria. Methods 262 adult patients with acute urticaria and in need of IV H1-antihistamine injections were randomized to either IV cetirizine or IV diphenhydramine. Primary efficacy was the “2-hour pruritus score change from baseline”. Key secondary endpoints were “time spent in treatment center” and “need to return to ED/clinic within 48 hours”. Patient sedation was scored at 1 hour, 2 hours, and discharge. Results The “2-hour pruritus score change from baseline” from IV cetirizine was demonstrated to be statistically non-inferior to IV diphenhydramine, and in favor of cetirizine. “Time spent in treatment center” was 2.07 hours in the diphenhydramine group and 1.71 hours in cetirizine (per protocol p=0.0024). “Return to ED/Clinic” was 14% in the diphenhydramine group and 5.5% in cetirizine (p=0.0232). Data also showed significantly less sedation in the cetirizine group at 1hr (p=0.0034), 2hr (p=0.0292), and at discharge (p=0.0443) compared to diphenhydramine. Conclusions IV cetirizine is an effective alternative to IV diphenhydramine in the treatment of acute urticaria with benefits of less sedation, less AE, earlier discharge, less symptom recurrence, and less return to treatment center.

Summary Background The bronchodilatory effect of mometasone furoate/formoterol fumarate (MF/F) administered by metered-dose inhaler (MDI) with or without a spacer has not been evaluated previously in children aged 5–11 years. Methods This was a randomized, multicenter, placebo-controlled, single-dose, four-period crossover study. Children with persistent asthma aged 5–11 years participated in this study. Subjects used inhaled corticosteroids with/without long-acting beta-2 agonists for 12 weeks before enrollment and at screening had forced expiratory volume in 1 sec (FEV1) ≥70% predicted. Subjects received MF/F MDI 100/10 µg with/without spacer (AeroChamber Plus® with Flow-Vu® Anti-Static Valved Holding Chamber), F-Dry Powder Inhaler (F-DPI) 10 µg, and placebo MDI with/without spacer in separate treatment periods. The primary endpoint was FEV1 area under the curve from 0 to 12 hr (AUC0–12hr) for the comparison of MF/F with spacer versus placebo. Secondary measurements included MF/F without spacer versus placebo, as well as MF/F with spacer versus MF/F without spacer, and F-DPI versus placebo. Analysis was performed with an analysis of covariance model for a crossover study. Results Data from 87 subjects were analyzed. MF/F with spacer demonstrated a larger change in mean FEV1 AUC0–12hr versus placebo (115 vs. −9 mL), with a treatment difference of 124 mL (95% CI 94–154, P

Patients with chronic idiopathic urticaria/chronic spontaneous urticaria (CIU/CSU) often continue to experience symptoms despite receiving standard-of-care therapy with H1-antihistamines along with 1 or more add-on therapies.We sought to evaluate the safety and efficacy of 24 weeks of treatment with omalizumab in patients with persistent CIU/CSU despite treatment with H₁-antihistamines at up to 4 times the approved dose plus H₂-antihistamines, leukotriene receptor antagonists, or both.In this phase III study patients were randomized to receive 6 subcutaneous injections at 4-week intervals of either 300 mg of omalizumab or placebo, followed by a 16-week observation period. The primary objective of the study was to evaluate the overall safety of omalizumab compared with placebo. Efficacy (itch severity, hive, and urticaria activity scores) was evaluated at weeks 12 and 24.The overall incidence and severity of adverse events and serious adverse events were similar between omalizumab and placebo recipients; the safety profile was consistent with omalizumab in patients with allergic asthma. At week 12, the mean change from baseline in weekly itch severity score was -8.6 (95% CI, -9.3 to -7.8) in the omalizumab group compared with -4.0 (95% CI, -5.3 to -2.7) in the placebo group (P.001). Significant improvements were seen for additional efficacy end points at week 12; these benefits were sustained to week 24.Omalizumab was well tolerated and reduced the signs and symptoms of CIU/CSU in patients who remained symptomatic despite the use of H₁-antihistamines (up to 4 times the approved dose) plus H₂-antihistamines, leukotriene receptor antagonists, or both.

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.

Inhaled corticosteroids administered by dry powder inhaler (DPI) or metered-dose inhaler are potent anti-inflammatory agents recommended for management of persistent asthma. Respiratory pharmacotherapy is unique in that proper delivery of the medication can be as important as the medication that is delivered. This study was designed to assess the mass median aerodynamic diameter (MMAD) of mometasone furoate (MF) particles from the 100- and 200-microgram/inhalation strength Twisthhaler (Merck & Co., Inc., Whitehouse Station, NJ) and to examine clinical effects of MF-DPI on midexpiratory flow. The MMAD with 100- and 200-microgram Twisthaler inhalers was analyzed using an Anderson cascade impactor. Clinical trial data for MF-DPI administered q.d. in the evening (P.M.) in adults and adolescents aged ≥12 years, as well as children aged 4-11 years, were examined post hoc for changes in forced expiratory flow between 25 and 75% of vital capacity (FEF(25-75)). The average MMAD of the 100-microgram strength Twisthaler (n = 24) was 2.0 micrometers; the average MMAD of the 200-microgram strength Twisthaler (n = 24) was 2.2 micrometers. In adults and adolescents (n = 1149), significant improvements in FEF(25-75) occurred with MF-DPI administered q.d. P.M. versus placebo (p ≤ 0.05). In children (n = 296), FEF(25-75) improved significantly with MF-DPI at 100 microgram q.d. P.M. versus placebo at day 4 and every visit thereafter (p ≤ 0.05). In vitro study suggests that the particle size of MF is optimal (~2 micrometers) for efficient lung deposition when administered via the Twisthaler. Furthermore, randomized, controlled trials provide clinical evidence that MF-DPI q.d. treatment improves small airway function in patients with mild persistent or moderate asthma.

Background A new, hydrofluoroalkane nasal aerosol solution formulation of ciclesonide (CIC-HFA) delivered via a metered dose inhaler is currently in clinical development for treatment of allergic rhinitis. Objective To study tolerability and quality of life following administration of CIC-HFA 74- or 148-μg doses once-daily compared with placebo in patients with perennial allergic rhinitis (PAR) over 26 weeks. Methods Patients ≥12 years of age with a ≥2 year history of PAR were randomized in a placebo-controlled, double-blind, parallel group, multicenter study to CIC-HFA 74 μg, 148 μg, or placebo QD AM for 26 weeks. Safety was assessed by monitoring treatment-emergent adverse events (TEAEs). Quality of life was assessed by using a rhinoconjunctivitis quality of life questionnaire with standardized activities (RQLQ[S]) in patients with baseline RQLQ ≥3.00. Reflective total nasal symptom scores (rTNSS) and instantaneous total nasal symptom scores (iTNSS) over 26 weeks were also evaluated. Results In this study, 1111 patients were randomized. The overall incidence of TEAEs was comparable between the treatment groups. Treatment with CIC-HFA 74- or 148-μg doses showed improvements in RQLQ[S] [least squares (LS) mean change 0.40 and 0.37, respectively from baseline, p < 0.01 versus placebo for both], rTNSS (LS mean change 0.65 and 0.52, respectively from baseline; p ≤ 0.01 versus placebo for both), and iTNSS (LS mean change 0.51 and 0.42, respectively from baseline; p < 0.05 versus placebo for both) from baseline. Conclusion In this study, once-daily treatment with CIC-HFA 74- or 148-μg doses over 26 weeks was well tolerated with comparable incidence of TEAEs between the treatment groups.

Mometasone furoate and formoterol fumarate dihydrate (MF/F) administered via metered-dose inhaler with a dose counter is a new fixed-dose combination of an inhaled corticosteroid and a long-acting β2-agonist indicated for daily maintenance therapy in patients aged ≥12 years with persistent asthma. Randomized, controlled trials have suggested that MF/F reduces asthma deteriorations while improving lung function and other measures of asthma control, including quality-of-life. Clinical safety studies lasting up to 1 year have found that MF/F has a low incidence of local and systemic side effects.

Objective Budesonide/formoterol inhalation aerosol (Symbicort AstraZeneca, Wilmington, Delaware) is an inhaled corticosteroid (ICS) and long-acting beta(2)-adrenergic agonist (LABA) combination administered twice daily via one hydrofluoroalkane pressurized metered-dose inhaler (pMDI) approved in the United States for the long-term maintenance treatment of persistent asthma in patients >or=12 years of age whose asthma cannot be controlled by an ICS alone. The objective was to review efficacy, safety, and pharmacogenetic data on budesonide/formoterol pMDI in the treatment of persistent asthma. Methods The authors searched PubMed and respiratory meeting databases to identify asthma studies of budesonide/formoterol pMDI. Studies involving traditional and patient-reported outcomes, safety, tolerability, or pharmacogenetics were included. Results In two 12-week pivotal trials in adolescents and adults, treatment with budesonide/formoterol pMDI 160/4.5 microg x 2 inhalations (320/9 microg) twice daily for moderate to severe persistent asthma or 80/4.5 microg x 2 inhalations (160/9 microg) twice daily for mild to moderate persistent asthma, demonstrated greater efficacy and similar tolerability compared with placebo and the same nominal dose of its monocomponents. Comparisons with formoterol dry powder inhaler (DPI) for predose forced expiratory volume in one second (FEV(1)) and with budesonide pMDI for 12-hour mean postdose FEV(1) demonstrated the anti-inflammatory and bronchodilatory contributions of budesonide and formoterol, respectively. Evaluations of patient-reported outcomes, including asthma-specific quality of life and treatment satisfaction, further supported the clinical benefits of budesonide/formoterol pMDI. In a 52-week tolerability study of patients aged >or=12 years, budesonide/formoterol pMDI was delivered at up to double the maximum dose (640/18 microg twice daily) and demonstrated a safety profile similar to that of budesonide (640 microg twice daily), with no unexpected pattern of abnormalities. Additional studies reported that budesonide/formoterol pMDI 320/9 microg twice daily and fluticasone propionate/salmeterol DPI 250/50 microg twice daily have similar efficacy and tolerability, with significantly more patients achieving >or=15% improvement in FEV(1) within 15 minutes with budesonide/formoterol pMDI compared with fluticasone/salmeterol DPI. Moreover, inheritance of the Gly16Arg polymorphism of the beta(2)-adrenergic receptor does not appear to affect clinical outcomes with budesonide/formoterol pMDI. Conclusion Budesonide/formoterol pMDI administered twice daily is effective and generally well tolerated in patients whose asthma is not well controlled on ICS alone.

Intranasal azelastine hydrochloride (Astelin, Meda Pharmaceuticals, Somerset, NJ, USA) is a first-line treatment for allergic and non-allergic vasomotor rhinitis with well-established therapeutic efficacy and safety. A new formulation of azelastine nasal spray (Astepro, Meda Pharmaceuticals, Somerset, NJ, USA), with a sorbitol-based vehicle and sucralose as a taste-masking agent, was developed to reduce the bitter taste of azelastine experienced by some patients.Two studies were conducted to evaluate the safety, tolerability and pharmacokinetic parameters of this new formulation compared with the original azelastine nasal spray.In a pharmacokinetic study, 18 healthy volunteers received either a single dose of the new formulation or the original formulation and pharmacokinetic parameters were determined. In a 1-year safety study, patients with chronic rhinitis were randomized to the new formulation (n = 430) or the original formulation (n = 432) to assess tolerability and the potential for adverse effects on the nasal mucosa.The new formulation was safe and well tolerated with long-term use and had a comparable pharmacokinetic profile to the original formulation. The overall incidence of treatment-emergent adverse events with the new formulation (48.4%) and the original formulation (49.1%) was similar, with no evidence of increased nasal irritation, nasal septal perforation, severe epistaxis or ulceration with either formulation during the 1-year study.

Two double-blind studies in children aged 6 to 11 years with allergic rhinitis (AR) assessed the efficacy and safety of the intranasal corticosteroid ciclesonide. In the first study, 618 patients w...

Despite remarkable advances in diagnosis and long-term management, asthma remains a serious public health concern. Newly updated expert guidelines emphasize the intra- and inter-individual variability of asthma and highlight the importance of periodic assessment of asthma control. These guidelines update recommendations for step-wise asthma treatment, address the burgeoning field of asthma diagnostics, and stress the importance of a patient and health care professional partnership, including written action plans and self monitoring. The field of asthma therapeutics is expanding rapidly, with promising new treatment options available or in development that may address some of the existing barriers to successful asthma management. These approaches simplify treatment, use combinations of agents in one delivery device that have complementary actions, or target specific pathways involved in asthma patho-physiology. Considerable activity is taking place in asthma pharmacogenetics. This review provides an overview of these new approaches to managing asthma, including their present status and future potential.

Devices for the aqueous delivery of intranasal corticosteroids to patients with allergic rhinitis have been available since 1984, so there is a need for new devices to be developed to provide ease of use, efficacy and safety. A novel drug delivery system has been developed for fluticasone furoate (FF; GlaxoSmithKline): a new enhanced-affinity glucocorticoid with a scent-free formulation. The FF system was developed, giving attention to patients' unmet needs, in order to promote acceptance and compliance. It demonstrates a number of key features including its ergonomic design, side-actuation system and short delivery nozzle. Exploiting issues with present devices highlighted the need for the FF system. This review reports data from key studies and surveys conducted by GlaxoSmithKline during development, to determine ease of use and acceptance of the FF system. Findings suggest that the FF system should aid in improving attitudes to the use of intranasal corticosteroids amongst physicians and patients.

Background A controlled-release (CR) formulation of zileuton was developed to simplify administration from 600 mg 4 times daily (Zyflo) to 1,200 mg twice daily. Objective To evaluate the efficacy of zileuton CR, two 600-mg tablets twice daily, compared with placebo. Methods Patients with moderate asthma treated with short-acting β-agonists only were randomized to receive zileuton CR, 1,200 mg twice daily (n = 206); placebo CR, twice daily (n = 203); zileuton immediate-release (IR), 600 mg 4 times daily (n = 101); or placebo IR, 4 times daily (n = 103), for 12 weeks. The primary efficacy variable was change from baseline in morning trough forced expiratory volume in 1 second (FEV 1 ). Results Improvement in trough FEV 1 was observed after 2 weeks of treatment ( P = .001) and was maintained throughout the study. After 12 weeks of dosing, FEV 1 improved by a mean of 0.39 L (20.8%) in the zileuton CR group vs 0.27 L (12.7%) in the placebo CR group ( P = .02). A significant decline in β-agonist use and a smaller proportion of patients reporting asthma exacerbations were observed in the zileuton CR group vs the placebo CR group. Adverse event profiles were similar across treatment groups. Elevations in alanine aminotransferase levels at least 3 times the upper limit of normal that reversed after drug withdrawal were seen in 5 zileuton CR-treated patients (2.5%) vs 1 placebo CR-treated patient (0.5%). Conclusions Treatment with zileuton CR, 1,200 mg twice daily, resulted in a significant improvement in asthma control, and the safety and efficacy profile was similar to that observed with zileuton IR, 600 mg 4 times daily (Zyflo).

Olopatadine hydrochloride ophthalmic solution 0.2% is a new once-daily formulation of olopatadine that is indicated for the treatment of ocular itching associated with allergic conjunctivitis. This formulation has demonstrated a safety, efficacy and comfort profile similar to that of olopatadine 0.1%. The advantages of once-daily dosing, however, may include cost-effectiveness, improvement in patient compliance and an improvement in quality of life. This review article will summarize literature reports on the 0.2% formulation of olopatadine from the standpoint of efficacy, safety, total treatment costs, therapeutic outcomes, patient compliance and effect on quality of life.

Nonallergic rhinitis in children is a medical condition that has not been well defined and the true incidence is unknown. Current treatment recommendations are based on data obtained from adult studies. The mechanisms of pediatric nonallergic rhinitis are also unclear. The concept that laryngopharyngeal reflux (LPR) events may play a critical role in the pathogenesis of upper air-way disease is presently under investigation. Although LPR is being better delineated and appropriate methods of diagnosis and treatment are being studied, substantial evidence links LPR with several disease states including rhinitis, sinus disease, and middle ear disease. Due to the lack of information concerning the etiology of nonallergic rhinitis in children, LPR should be considered in the differential diagnosis of a child with negative skin tests and chronic rhinitis symptoms. The clinician should especially give attention to this diagnosis when a child presents with recurrent co-morbid conditions such as chronic sinusitis or persistent middle ear disease.

Ciclesonide is an intranasal corticosteroid approved for the treatment of allergic rhinitis (AR).To evaluate the efficacy, safety, and quality-of-life benefits of intranasal ciclesonide, 200 microg once daily, for the treatment of perennial AR (PAR).In this multicenter, randomized, double-blind, placebo-controlled study, adults and adolescents with at least a 2-year history of PAR received intranasal ciclesonide, 200 microg, or placebo once daily for 6 weeks. Patient-evaluated total nasal symptom scores (TNSSs), physician-assessed overall nasal signs and symptoms severity scores, and Rhinoconjunctivitis Quality of Life Questionnaire scores were evaluated.Patient baseline characteristics were similar in the ciclesonide (n = 238) and placebo (n = 233) groups and were consistent with moderate PAR severity. Ciclesonide therapy significantly reduced average morning and evening reflective TNSSs compared with placebo (P.001) and significantly reduced average morning and evening instantaneous TNSSs (P = .001) over 6 weeks of treatment. At the end point, a greater decrease from baseline was observed in physician-assessed overall nasal signs and symptoms severity for the ciclesonide group compared with the placebo group (P = .051). An appreciable improvement in combined Rhinoconjunctivitis Quality of Life Questionnaire scores at the end point was also observed in the ciclesonide group (P = .01 vs placebo). The frequency of adverse events was similar between treatment groups.In this study, intranasal ciclesonide treatment was associated with significant reductions in nasal symptoms and appreciable improvements in health-related quality of life in adult and adolescent patients with PAR. Ciclesonide was well tolerated, with a safety profile comparable with that of placebo.

Background Beclomethasone dipropionate (BDP) nasal aerosol (non-aqueous) is approved for management of seasonal and perennial allergic rhinitis (PAR) in adolescents and adults. Objective To evaluate the efficacy and safety of BDP nasal aerosol at 80 μg/day in children with PAR. Methods This 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. Results Improvements 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. Conclusion The 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 Registration www.clinicaltrials.gov, identifier NCT01783548.

BACKGROUND: Inadequate designs and conflicting results from previous studies prompted the US Food and Drug Administration to publish guidelines for the design of clinical trials evaluating the effects of orally inhaled and intranasal corticosteroids on the growth of children. This study conformed to these guidelines to evaluate the effect of triamcinolone acetonide aqueous nasal spray (TAA-AQ) on the growth of children with perennial allergic rhinitis (PAR). METHODS: This randomized, double-blind, placebo-controlled, parallel-group, multicenter study evaluated the effect of once-daily TAA-AQ (110 μg) on the growth velocity (GV) of children aged 3–9 years with PAR by using stadiometry at baseline (4–6 months), during treatment (12 months), and at follow-up (2 months). Hypothalamus-pituitary-adrenal (HPA) axis function was assessed by measuring urinary cortisol levels. Details of adverse events were recorded. RESULTS: Of 1078 subjects screened, 299 were randomized, and 216 completed the study (placebo, 107; TAA-AQ, 109). In the primary analysis (modified intent-to-treat: placebo, 133; TAA-AQ, 134), least-squares mean GV during treatment was lower in the TAA-AQ group (5.65 cm/year) versus placebo (6.09 cm/year). The difference (–0.45 cm/year; 95% confidence interval: –0.78 to –0.11; P = .01), although clinically nonsignificant, was evident within 2 months of treatment and stabilized thereafter. At follow-up, the GV approached baseline (6.70 cm/year) in the TAA-AQ group (6.59 cm/year) and decreased slightly in the placebo group (5.89 cm/year vs 6.06 cm/year at baseline). No HPA axis suppression was observed. CONCLUSIONS: By using rigorous Food and Drug Administration–recommended design elements, this study detected a small, statistically significant effect of TAA-AQ on the GV of children with PAR.

Inhaled corticosteroids (ICS) are recommended first-line therapy for patients with asthma of all severities. Prolonged exposure to high-dose ICS can cause systemic and oropharyngeal adverse events. Minimizing ICS-related adverse events by selecting an ICS with an improved safety profile may increase patients' adherence to their asthma treatment. Ciclesonide, a novel ICS currently under development, is a parent compound that is converted in the lungs by endogenous esterases to its active metabolite, desisobutyryl-ciclesonide. Reported data suggest that ciclesonide is well tolerated, with no observed effect on hypothalamic-pituitary-adrenal (HPA)-axis function and a low incidence of oropharyngeal adverse events (comparable with placebo). These safety benefits, observed in children and adults with asthma, may be due to ciclesonide's favorable pharmacokinetic/pharmacodynamic properties. The lack of HPA-axis function suppression may be due to the low oral bioavailability, high serum protein binding and rapid apparent systemic clearance reported with desisobutyryl-ciclesonide. The low incidence of oropharyngeal adverse events may be attributed to the low oral deposition of ciclesonide in the oropharynx and its limited conversion to desisobutyryl-ciclesonide. The favorable safety profile of ciclesonide suggests a conferred benefit to asthma patients treated with this novel ICS.

Objective To discuss the clinical efficacy and safety of formoterol when used to relieve symptoms of asthma and prevent exercise-induced bronchoconstriction (EIB). Data Sources A PubMed search was performed for articles published between 1997 and 2005 with the keywords formoterol , asthma , and long-acting β 2 -adrenergic agonist, with cross-referencing to identify peer-reviewed journal articles. Study Selection Published articles on the clinical use of formoterol for asthma or EIB were included as well as articles detailing the pharmacologic properties of the drug. To present a thorough review of the literature, published studies based on patient number, study design, or other measures of study quality were not excluded. Results Formoterol is the only long-acting β 2 -adrenergic agonist that combines a rapid onset of action (within 3 minutes) with a long duration of effect (approximately 12 hours). Clinically, as recommended by asthma treatment guidelines, formoterol in conjunction with inhaled corticosteroids (ICSs) is a preferred treatment for moderate to severe persistent asthma. Significant clinical data support the use of formoterol in combination with ICSs for the treatment of asthma, with studies demonstrating improved pulmonary function and symptom scores and decreased need for maintenance ICSs and short-acting β 2 -adrenergic agonists (SABAs) as relief medication. Recent studies also demonstrate that use of formoterol as needed as relief medication is associated with a prolonged time to exacerbation, improved pulmonary function, and decreased asthma symptoms. When used as monotherapy, formoterol provides protection against EIB. Clinical data also demonstrate that formoterol is safe and well tolerated even in high doses, with an adverse event profile similar to that of SABAs. Conclusion Overall, formoterol is safe and effective as adjunct controller therapy for moderate and severe persistent asthma and as monotherapy for EIB.

To evaluate the efficacy and safety of levalbuterol metered dose inhaler (MDI) in children aged 4-11 years (n = 173).Multicenter, randomized, double-blind 28-day study of QID levalbuterol 90 microg, racemic albuterol 180 mug, and placebo (2:1:1 ratio). Serial spirometry was performed on Days 0, 14, and 28. The primary endpoint was the double-blind average peak percent (%) change in FEV(1) from visit pre-dose; the primary comparison was with placebo. Secondary endpoints included the area under the FEV(1) percent change from pre-dose curve and peak % predicted FEV(1). Safety endpoints included adverse events, laboratory tests, rescue medication use, and electrocardiograms.Levalbuterol significantly improved the least square mean peak percent change in FEV(1) compared with placebo (levalbuterol 25.6% +/- 1.3% [p0.001]; racemic albuterol 21.8% +/- 1.8% [p = ns]; placebo 16.8% +/- 1.9%). Results for levalbuterol were similar for the other spirometry endpoints (p0.05 vs. placebo). No levalbuterol-treated patients had a peak percent change in FEV(1)10% (compared with 15.8% of racemic albuterol-treated patients and 30.3% of placebo-treated patients). The incidence of adverse events was 43.4% for levalbuterol, 56.4% for racemic albuterol, and 51.4% for placebo. The rate of discontinuation was 1.3% for levalbuterol, 2.6% for racemic albuterol, and 8.6% for placebo. The rate of asthma attacks (10.5%, 12.8%, 14.3%, respectively) was similar among treatments. Levalbuterol and racemic albuterol both reduced rescue medication use (p0.01 vs. placebo) and produced changes in ventricular heart rate and QT(c-F) that were similar to placebo.In this study, levalbuterol administered via MDI significantly improved airway function in comparison with placebo in asthmatic children aged 4-11 years with a safety profile that was similar to placebo.

This is the first U.S.-based study to compare efficacy and safety of desloratadine with fexofenadine in subjects with symptomatic seasonal allergic rhinitis (SAR). In this double-blind study, subjects were randomized to desloratadine, 5 mg (n = 290),fexofenadine, 180 mg (n = 288), or placebo (n = 144) once daily for 15 days. Primary end point was mean change from baseline to study end in morning instantaneous total symptom score (AM NOW TSS) excluding congestion. Secondary measures included change from baseline in the morning/evening reflective TSS (AM/PM PRIOR TSS) excluding congestion, AM NOW individual symptom score (AM NOW ISS) including congestion, and the AM/PM PRIOR ISS including congestion. Subjects self-evaluated their symptoms on a five-point scale. Mean AM NOW TSSs were significantly reduced from baseline at day 15 with desloratadine (p = 0.006) and fexofenadine (p = 0.024) versus placebo. Desloratadine and fexofenadine were not statistically different (p = 0.491); the upper limit of the 95% CI for desloratadine to fexofenadine (0.259) was within the prespecified noninferiority margin of 0.7 U. Decrease in mean AM/PM PRIOR TSS excluding congestion was comparable between desloratadine and fexofenadine (p = 0.405; CI = 0.221) but was significantly greater with both active treatments versus placebo (desloratadine, p < 0.001;fexofenadine, p = 0.003). Desloratadine and fexofenadine provided greater reduction in the AM NOW ISS and AM/PM PRIOR ISS (both including congestion) versus placebo; reductions were comparable between active treatments. All treatments were well tolerated. Desloratadine, 5 mg, and fexofenadine, 180 mg, provide comparable efficacy and tolerability in the treatment of SAR. Both treatments are significantly more effective than placebo.

BACKGROUND A recent survey estimated that 85% of patients with allergic rhinitis experience nasal congestion. This symptom considerably impacts quality of life. OBJECTIVE To evaluate the effectiveness of mometasone furoate nasal spray (MFNS) in subjects with seasonal allergic rhinitis (SAR) experiencing moderate-to-severe nasal congestion. METHODS Data were obtained from 4 randomized, double-blind, placebo-controlled studies of MFNS 200 μg once daily in patients with SAR. Subject-evaluated nasal congestion score data (score range 0–3) from subjects receiving MFNS or placebo were analyzed as a pool and grouped according to baseline score (all pts. with scores >2.5, >2.75, or 3.0). The 2-week average change in score from baseline was analyzed. RESULTS Significant improvements in mean nasal congestion score were seen with MFNS (n = 490) versus placebo (n = 492; p < 0.001). Overall, there was a 27% improvement in this score in patients receiving MFNS versus 13% with placebo. MFNS produced significant reductions in the nasal congestion score compared with placebo, even in patients with the most severe baseline congestion (0.98 vs 0.52; p < 0.001). Improvements in scores from baseline of 32%, 33%, and 34% were seen with MFNS versus 22%, 21%, and 18% with placebo (for baseline scores of >2.5, >2.75, or 3.0, respectively), confirming the effectiveness of MFNS regardless of congestion severity. This represents an improvement approximating a decrease from severe to moderate congestion or from moderate-to-severe to mild-to-moderate congestion. MFNS was well tolerated. CONCLUSIONS MFNS 200 μg once daily produces statistically significant improvements in nasal congestion score compared with placebo, alleviating severe congestion in patients with moderate-to-severe SAR.

induced after allergen exposure by an immunoglobulin E (IgE)mediated inflammation of the nasal membranes. The disease is most often classified as seasonal (SAR) or perennial (PAR) allergic rhinitis, or using the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines, intermittent or persistent, depending on the duration and frequency of symptoms. The evidence-based ARIA guidelines were developed by expert panels in collaboration with the World Health Organization (WHO),4 and still serve as a useful reference point for the treatment of AR. Because more children suffer from SAR than PAR,4 SAR will form the focus of this review; in cases where a distinction is not made between the two conditions in the literature, AR will be used, with the supposition that most patients with AR have SAR. AR is primarily characterized by the familiar symptoms of sneezing, rhinorrhea, nasal congestion, and the associated symptoms of itchy nose, palate, throat, and/or ears, and itchy watery, and/or red eyes.4 Because these symptoms are not serious and do not endanger life, AR suffers from a reputation as a ‘lifestyle disease’ rather than a disease that seriously affects quality of life (QoL). In addition to the symptoms directly linked to the allergic response, AR is associated with generalized malaise, irritability, and fatigue.5 Indeed, it has been acknowledged in several consensus reports that AR seriously impairs day-to-day functioning;6,7 thus, the need to

Azelastine nasal spray and oral cetirizine are selective histamine H(1)-receptor antagonists that are approved in the United States for the treatment of seasonal allergic rhinitis (SAR).The objective of the present study was to compare the efficacy and tolerability of azelastine nasal spray administered at the recommended dosage of 2 sprays per nostril twice daily with those of cetirizine in the treatment of moderate to severe SAR.This multicenter, randomized, double-blind, parallel-group, 2-week comparative study was conducted during the 2004 fall allergy season in patients with moderate to severe SAR. After a 1-week placebo lead-in period, patients were randomized to receive azelastine nasal spray 2 sprays per nostril twice daily plus placebo tablets or cetirizine 10-mg tablets once daily plus a placebo saline nasal spray for the 2-week double-blind treatment period. The primary efficacy variables were (1) change from baseline to day 14 in the 12-hour reflective total nasal symptom score (TNSS), which combines scores for rhinorrhea, sneezing, itchy nose, and nasal congestion, and (2) onset of action, based on the instantaneous TNSS over 4 hours after the first dose of study drug. During the double-blind treatment period, patients recorded their symptom scores on diary cards twice daily (morning and evening). Patients agedor =18 years also completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) at baseline and on day 14.Three hundred seven patients were randomized to treatment, and 299 completed 2 weeks of study treatment. The age of the population ranged from 12 to 74 years (mean, 35 years), 62.9% were female, and 69.6% were white. Over 2 weeks of treatment, both groups had significant improvements in the TNSS compared with baseline (P0.001). The overall change in TNSS was significantly greater with azelastine nasal spray compared with cetirizine (29.3% vs 23.0% improvement, respectively; P = 0.015). In terms of onset of action, azelastine nasal spray significantly improved the instantaneous TNSS compared with cetirizine at 60 and 240 minutes after the initial dose (both, P = 0.040). Scores on each domain of the RQLQ were significantly improved in both groups compared with baseline (P0.001); the overall RQLQ score was significantly improved with azelastine nasal spray compared with cetirizine (P = 0.049). Both treatments were well tolerated.In this 2-week study in patients with moderate to severe SAR, azelastine nasal spray was well tolerated and produced significantly greater improvements in TNSS and total RQLQ score compared with cetirizine.

Inhaled corticosteroids are recommended first-line therapy for asthma of all severities. Concerns regarding local and systemic side effects can influence adherence, and subsequently, efficacy and long-term asthma control. Ciclesonide is a novel inhaled corticosteroid with an improved therapeutic margin – its efficacy is similar to that of other inhaled corticosteroids, but with a potentially better local and systemic safety profile in patients with persistent asthma. Ciclesonide is activated, mainly in the lung, to desisobutyryl-ciclesonide, the active metabolite, which, together with its other pharmacokinetic properties, contributes to its improved safety profile. Additionally, the drug is delivered through a hydrofluoroalkane metered-dose inhaler, which allows high lung deposition and delivery into the small airways. The improved therapeutic margin of ciclesonide may increase patient adherence, thereby ultimately improving asthma control.

Background The Health Plan Employer Data and Information Set (HEDIS) measures are used extensively to measure quality of care. Objective To evaluate selected aspects of the HEDIS measure of appropriate use of asthma medications. Methods Claims data were analyzed for commercial health plan members who met HEDIS criteria for persistent asthma in 1999. The use of asthma medications was evaluated in the subsequent year with stratification by controller medication and a measure of adherence (days' supply). Multivariate logistic regressions were used to evaluate the association among long-term controller therapy for persistent asthma, adherence to therapy, and asthma-related hospitalizations or emergency department (ED) visits, controlling for demographic, preindex utilization, and other confounding characteristics. Results Of the 49,637 persistent asthma patients, approximately 35.7% were using 1 class of long-term controller medications, 18.4% were using more than 1 class, and 45.9% were not using such medication. More than 25% of the persistent asthma patients did not use any asthma medication in the subsequent year. Patients with low adherence to controller medication had a significantly higher risk (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.42–2.08) of ED visit or hospitalization relative to patients not using any controllers compared with persons with moderate (OR, 0.84; 95% CI, 0.57–1.23) or high (OR, 0.70; 95% CI, 0.34–1.44) adherence. Patients receiving a high days' supply of inhaled corticosteroids had the lowest risk of ED visit or hospitalization (OR, 0.37; 95% CI, 0.05–2.69). Conclusions Our findings suggest that refinements to the HEDIS measure method for identifying patients with persistent asthma may be needed.