MP-AzeFlu in Moderate-to-Severe Allergic Rhinitis: A Literature Review.

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.

A generic fluticasone propionate and salmeterol dry powder inhaler: Evidence of usability, function, and robustness.

Background: A generic combination of fluticasone propionate and salmeterol xinafoate inhalation powder in a premetered, multidose, nonreusable inhaler was recently approved. Objective: To assess the performance of the generic device. Methods: Findings from three studies with regard to device usability, function, and robustness were reviewed. Results: In a study to assess device function in patients and healthy volunteers, the generic device was successfully used by patients with asthma and chronic obstructive pulmonary disease who were either dry powder inhaler users or dry powder inhaler-naive, even though they were not trained beyond being provided the instructions for use. In a study to measure inhaled flow rates generated by patients and healthy volunteers, the generic device consistently simulated the delivery of a full dose of drug, even to patients with severe respiratory disease and reduced inspiratory flow rates. Although the generic device had a slightly higher airflow resistance, this study demonstrated that this difference did not result in any clinically meaningful differences in terms of drug delivery. Pressure drop, a key parameter that drives the fluidization and aerosolization of the powder dose, was found to be comparable between the devices. In an open-label study, the generic device met all U.S. Food and Drug Administration specifications for device robustness after 21.5 days of twice-daily dosing via oral inhalation among 111 participants with asthma or chronic obstructive pulmonary disease. All inhalers tested demonstrated conformity with a pharmacopeia with respect to key quality parameters (assay, delivered dose uniformity, aerodynamic size distribution). There was no evidence of chemical degradation of the active ingredients, nor of microbial or water ingress into the powder, as a result of inhaler use.

Effect of Specific Immunoglobulin E Response and Comorbidities on Effectiveness of MP-AzeFlu in a Real-Life Study.

INTRODUCTION: Phenotyping allergic rhinitis (AR) by immunoglobulin E (IgE) sensitivity and comorbidities may help characterize AR and provide a framework for treatment decisions. METHODS: This prospective, noninterventional study evaluated the effectiveness of MP-AzeFlu (azelastine hydrochloride plus fluticasone propionate intranasal spray formulation) across AR phenotypes. Patients with moderate-to--severe seasonal or perennial AR for whom MP-AzeFlu was prescribed were enrolled. AR subpopulations (ARPs) were assigned based on the classification of IgE response and comorbidities. AR symptoms over the previous 24 h were documented using an AR visual analog scale (AR-VAS), with ratings from "not at all bothersome" (0 mm) to "extremely bothersome" (100 mm), at the inclusion visit and on days 1, 3, 7, and the last day of the study (approximately day 14). AR quality-of-life measures were recorded using a VAS. RESULTS: A total of 1,103 patients with AR were included. Mean baseline AR-VAS scores ranged from 70.3 to 75.1 mm (severe) across ARPs. In the overall population, 86.6% of patients responded to treatment (AR-VAS score <50 mm on ≥1 days). In the ARPs, response rates ranged from 79.3 to 89.6%. Mean reduction in AR-VAS scores ranged from 47.9 to 40.9 mm, a decrease from severe to mild across all ARPs. Quality-of-life VAS scores were similarly reduced in the total population and ARPs. DISCUSSION/CONCLUSION: MP-AzeFlu treatment reduced VAS severity and quality-of-life scores from baseline in the total population and ARPs, supporting MP-AzeFlu as an effective treatment for all patients with moderate-to-severe AR, regardless of AR phenotype or comorbidities.

Allergic rhinitis and asthma symptoms in a real-life study of MP-AzeFlu to treat multimorbid allergic rhinitis and asthma.

BACKGROUND: Asthma affects up to nearly 40% of patients with allergic rhinitis (AR). Poor control of AR symptoms is associated with poor asthma control. The goal of this study was to evaluate the effect of AR treatment with MP-AzeFlu on symptoms of AR as well as symptoms of asthma. METHODS: This prospective study used a visual analog scale (VAS) to assess symptoms of AR and asthma before and after treatment with MP-AzeFlu (Dymista®; azelastine hydrochloride plus fluticasone propionate; 1 spray in each nostril twice daily for 2 weeks). Participants suffered from moderate-to-severe AR according to Allergic Rhinitis and its Impact on Asthma criteria, with acute AR symptoms (AR-VAS scores ≥ 50 mm) on inclusion day. In addition to symptom assessment, patients recorded the impact of AR symptoms on quality-of-life measures before, during, and at the conclusion of the treatment period (approximately 14 days). Patients self-reported change in frequency of their usage of asthma reliever medication on the last day of treatment. RESULTS: Of 1103 study participants, 267 (24.2%) had comorbid asthma. These participants reported using a mean of 5.1 puffs of asthma reliever medication in the week before treatment with MP-AzeFlu. A total of 81.8% of patients with comorbid asthma responded to AR therapy (AR-VAS < 50 mm on at least 1 study day). Among patients with AR and comorbid asthma, MP-AzeFlu was associated with improved VAS scores across all study parameters, including AR symptom severity, asthma symptom severity, sleep quality, daily work or school activities, daily social activities, and daily outdoor activities. Asthma symptom severity decreased from a mean of 48.9 mm to 24.1 mm on the VAS. Self-reported frequency of asthma reliever medication use was reduced for 57.6% of participants (n = 139/241). CONCLUSION: MP-AzeFlu used to relieve AR symptoms was associated with reduced asthma symptom VAS scores and frequency of asthma reliever medication usage. Changes in overall symptoms of AR and asthma were correlated.

Deposition characteristics of a novel intranasal formulation of azelastine hydrochloride plus fluticasone propionate in an anatomic model of the human nasal cavity.

Background: Intranasal antihistamines and steroids should be delivered in a volume and with a technique that allow for optimal drug retention within the entire nasal cavity, maximize local absorption by the nasal mucosa, and, subsequently, increase the potential for the most desirable local availability and therapeutic effect. Objective: This in vitro evaluation simulated nasal medication deposition and evaluated the extent of runoff. MP-AzeFlu, a novel intranasal formulation of azelastine hydrochloride (AZE) plus fluticasone propionate (FP), was compared with sequential sprays of available commercial products with the individual medication components. Methods: A model of a normal adult human nasal cavity was used to visualize deposition of nasal spray products. A single spray of MP-AzeFlu (0.137 mL [137 µg of AZE/50 µg of FP]) or single sequential sprays of AZE nasal spray (0.137 mL [137 µg]) followed by brand name or generic FP nasal spray (0.100 mL [50 µg]) were manually actuated into the model. The interior was coated with a water-sensitive dye that changes to magenta when exposed to aqueous-based formulations. A slight vacuum was applied during spray delivery to simulate sniffing. The results were photographed by using anterior and lateral views. Results: Three replicates of MP-AzeFlu showed no dripping from the front of the nostril or backflow from the nasal cavity. However, three replicates of AZE nasal spray, followed by a brand name or generic FP nasal spray, showed significant dripping from the front of the nostril and backflow from the nasal cavity. Conclusion: A single spray of MP-AzeFlu resulted in no runoff compared with sequential dosing of the two other therapeutic products. Product runoff is likely due to the volume exceeding the capacity of the nasal cavity model. Furthermore, the common clinical dosing regimen of two sprays per nostril of each of the individual components would promote even greater increased undesirable flooding and leakage.

Prevalence and Management of Chronic Obstructive Pulmonary Disease in the Gulf Countries with a Focus on Inhaled Pharmacotherapy.

Background: Chronic obstructive pulmonary disease (COPD) is a preventable, progressive disease and the third leading cause of death worldwide. The epidemiological data of COPD from Gulf countries are very limited, as it remains underdiagnosed and underestimated. Risk factors for COPD include tobacco cigarette smoking, water pipe smoking (Shisha), exposure to air pollutants, occupational dusts, fumes, and chemicals. Inadequate treatment of COPD leads to worsening of disease. The 2024 GOLD guidelines recommend use of inhaled bronchodilators, corticosteroids, and adjunct therapies for treatment and management of COPD patients based on an individual assessment of the severity of symptoms and risk of exacerbations. This article reviews COPD pharmacotherapy in the Gulf countries and explores the role of nebulization in the management of COPD in this region. Methods: To review the COPD pharmacotherapy in the Gulf Countries, literature search was conducted using PubMed, Medline, Cochrane Systematic Reviews, and Google Scholar databases (before December 2022), using search terms such as COPD, nebulization, inhalers/inhalation, aerosols, and Gulf countries. Relevant articles from the reference list of identified studies were reviewed. Consensus statements, expert opinion, and other published review articles were included. Results: In the Gulf countries, pressurized metered-dose inhalers (pMDIs), dry powder inhalers (DPIs), soft mist inhalers, and nebulizers are used for drug delivery to COPD patients. pMDIs and DPIs are most prone to errors in technique and other common device handling errors. Nebulization is another mode of inhalation drug delivery, which is beneficial in certain patient populations such as the elderly and patients with cognitive impairment, motor or neuromuscular disorders, and other comorbidities. Conclusion: There is no major difference between Gulf countries and rest of the world in the approach to management of COPD. Nebulizers should be considered for patients who have difficulties in accessing or using MDIs and DPIs, irrespective of geographical location.

Bridging the "Know-Do" Gaps in Five Non-Communicable Diseases Using a Common Framework Driven by Implementation Science.

According to the United Nations High-Level Meeting 2018, five non-communicable diseases (NCDs) including cardiovascular diseases, chronic respiratory diseases, diabetes mellitus, cancer, and mental health conditions accounted for two-thirds of global deaths. These five NCDs share five common risk factors including tobacco use, unhealthy diets, physical inactivity, alcohol use, and air pollution. Low- and middle-income countries (LMICs) face larger burden of NCDs than high-income countries (HICs), due to differences in ecological, technological, socioeconomic and health system development. Based on high-level evidence albeit mainly from HICs, the burden caused by NCDs can be reduced by affordable medicines and best practices. However, "know-do" gaps, ie, gaps between what we know in science and what we do in practice, has limited the impact of these strategies, especially in LMICs. Implementation science advocates the use of robust methodologies to evaluate sustainable solutions in health, education and social care aimed at informing practice and policies. In this article, physician researchers with expertise in NCDs reviewed the common challenges shared by these five NCDs with different clinical courses. They explained the principles of implementation science and advocated the use of an evidence-based framework to implement solutions focusing on early detection, prevention and empowerment, supplemented by best practices in HICs and LMICs. These successful stories can be used to motivate policymakers, payors, providers, patients and public to co-design frameworks and implement context-relevant, multi-component, evidence-based practices. In pursuit of this goal, we propose partnership, leadership, and access to continuing care as the three pillars in developing roadmaps for addressing the multiple needs during the journey of a person with or at risk of these five NCDs. By transforming the ecosystem, raising awareness and aligning context-relevant practices and policies with ongoing evaluation, it is possible to make healthcare accessible, affordable and sustainable to reduce the burden of these five NCDs.

The Role of ICS/LABA Fixed-Dose Combinations in the Treatment of Asthma and COPD: Bioequivalence of a Generic Fluticasone Propionate-Salmeterol Device.

Both asthma and chronic obstructive pulmonary disease (COPD) are inflammatory chronic respiratory conditions with high rates of morbidity and mortality worldwide. The objectives of this review are to briefly describe the pathophysiology and epidemiology of asthma and COPD, discuss guideline recommendations for uncontrolled disease, and review a new generic option for the treatment of asthma and COPD. Although mild forms of these diseases may be controlled with as-needed pharmacotherapy, uncontrolled or persistent asthma and moderate or severe COPD uncontrolled by bronchodilators with elevated eosinophilia or frequent exacerbations may require intervention with combination therapy with inhaled corticosteroids (ICS) and long-acting beta agonists (LABAs), according to international guidelines. Fixed-dose combinations of ICS/LABA are commonly prescribed for both conditions, with fluticasone propionate (FP) and salmeterol forming a cornerstone of many treatment plans. An oral inhalation powder containing the combination of FP and salmeterol has been available as Advair Diskus® in the United States for almost 20 years, and the first and only substitutable generic version of this product has recently been approved for use: Wixela™ Inhub™. Bioequivalence of Wixela Inhub and Advair Diskus has been established. Furthermore, the Inhub inhaler was shown to be robust and easy to use, suggesting that Wixela Inhub may provide an alternative option to Advair Diskus for patients with asthma or COPD requiring intervention with an ICS/LABA.

Allergic Rhinitis Therapy Decisions During a Routine Consultation: A Multicenter, Cross-Sectional Survey.

BACKGROUND: Allergic rhinitis (AR) is characterized by nasal and ocular symptoms, and substantially impacts the quality of life. Therapy selection for patients with AR depends on several factors, including symptom severity, age, patient preference, patient adherence, and cost. METHODS: The purpose of this multicenter, noninterventional, cross-sectional survey was to evaluate current therapy decisions in routine clinical practice for patients with symptomatic AR, and to determine how these decisions are linked to experiences with previous treatments and current symptom severity as assessed by aVAS. The survey included patients aged 18 years or older in Spain and 12 years or older in Hungary who consulted a physician for treatment of AR symptoms. Physicians recorded AR symptom burden in the previous 7 days, previous AR treatments, and the current AR therapy decision made at the visit. RESULTS: Overall, 72.9% of 181 patients (Spain) and 67.1% of 228 patients (Hungary) had received treatment in the previous 7 days. Among patients who had received step 3 treatment, 82.9% (Spain) and 75.8% (Hungary) received a free combination of intranasal corticosteroid (INCS) and antihistamines. Despite the high number of pretreated patients in both countries, 72.9% and 78.9% in Spain and Hungary, respectively, reported uncontrolled symptoms (VAS ≥50 mm). Of pretreated patients, 58.3% (Spain) and 61.4% (Hungary) received a step-up in treatment during the visit. Physicians more often prescribed a fixed combination of INCS and intranasal antihistamine than a free combination. However, of patients with uncontrolled symptoms who received previous therapy, 28.0% (Hungary) and 40.6% (Spain) did not receive a step-up as suggested by the guidelines. CONCLUSION: Many patients suffering from acute AR symptoms consulted with their physician because of insufficient medications. Not all patients with uncontrolled symptoms received a step-up in treatment, underscoring the need for improved physician education to enhance AR management and control in accordance with consensus treatment guidelines.

Wixela Inhub: A Generic Equivalent Treatment Option for Patients with Asthma or COPD.

PURPOSE: The purpose of this review is to discuss the development of Wixela™ Inhub™, a generic equivalent of Advair Diskus®, a fixed-dose combination of fluticasone propionate/salmeterol powder for oral inhalation for patients with asthma whose symptoms are not controlled with inhaled corticosteroids alone and for those with chronic obstructive pulmonary disease (COPD) who are at a high risk for exacerbations. We provide an overview of the Inhub device and the bioequivalence studies that have been conducted to date. Briefly, the in vitro performance, improvements in forced expiratory volume in 1 s, and the fluticasone propionate/salmeterol dose strengths for Wixela Inhub and Advair Diskus were comparable. CONCLUSION: The bioequivalence demonstrated by the totality of clinical and in vitro data supports the use of Wixela Inhub and provides a treatment option for patients with asthma or COPD.

The Wixela™ Inhub™ device has been developed as a generic equivalent of Advair Diskus^®, and provides a combination treatment for patients with asthma whose symptoms are not controlled with inhaled corticosteroids alone and for those with chronic obstructive pulmonary disease (COPD) who are at a high risk for exacerbations. We provide information about the Inhub device and studies conducted to show how Inhub and Diskus are comparable products. Based on the similar results between the two devices, Inhub can be used as a treatment option for patients with asthma or COPD.

Evaluation of in vitro Penetration of Fluticasone Propionate from MP-AzeFlu and Fluticasone Propionate Nasal Spray Through EpiAirway™606 Tissues Using Vertical Diffusion Cells.

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™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 µL of MP-AzeFlu (3.65 µg; n = 8) and 10 µL of FP nasal spray (5.00 µg; 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.

MP-AzeFlu Improves the Quality-of-Life of Patients with Allergic Rhinitis.

PURPOSE: Patients with poorly controlled allergic rhinitis (AR) experience nasal symptoms, sleep disturbances, activity impairment, and decreased quality-of-life (QoL). MP-AzeFlu is safe and effective for moderate-to-severe seasonal and perennial AR, but its impact on QoL requires investigation in the real-world, especially among phenotypes of immunoglobulin (Ig)E-mediated AR. This subanalysis of an observational study evaluated response to MP-AzeFlu via assessment of sleep quality and trouble with daily activities. PATIENTS AND METHODS: This multicenter, prospective, non-interventional, real-life study included a convenience sample of patients with a history of moderate-to-severe AR presenting with acute AR symptoms (visual analog scale [VAS] ≥50 mm). Over approximately 14 days of treatment with MP-AzeFlu (137 µg azelastine HCL and 50 µg fluticasone propionate administered via single 0.137-mL spray in each nostril twice daily), changes in sleep quality and trouble with daily work, school, social, and outdoor activities were evaluated using a VAS for the entire study population and for four subgroups based on IgE response phenotype. VAS scores ranged from "not at all troubled" (0 mm) to "extremely troubled" (100 mm). RESULTS: Following MP-AzeFlu treatment, mean VAS scores for sleep quality impairment and work or school impairment decreased from 55.2 mm at baseline to 22.1 mm and 57.6 mm at baseline to 23.0 mm, respectively, after ~14 days. Similar results were observed for mean VAS scores for impairment of social activity (55.1 mm to 22.4 mm) and impairment of outdoor activity (64.4 mm to 25.0 mm). For all VAS scores, results were similar across populations, regardless of phenotype of IgE-mediated disease, comorbidity, age, and sex. CONCLUSION: MP-AzeFlu relieves symptoms and improves patient-reported QoL, illustrated by better sleep quality and less impairment of work, school, social, and outdoor activities after 14 days. The QoL benefits of MP-AzeFlu were consistent regardless of the phenotype of IgE-mediated disease. REGISTRATION: Clinical Trial Registration (CTR) Number: EUPAS23075. Trial Register Date: March 12, 2018. First patient visit; Last patient visit: February 2018; April 2019.

Long-term safety and efficacy of formoterol fumarate inhalation solution in patients with moderate-to-severe COPD.

BACKGROUND: Formoterol fumarate inhalation solution (FFIS; Perforomist®) is a long-acting ß2-agonist (LABA) marketed in the US as a nebulized COPD maintenance treatment. Because long-term LABA use was associated with a potential increased risk of exacerbation or death in asthma patients, the US Food and Drug Administration (FDA) requested a postmarketing commitment study to evaluate long-term safety in COPD patients. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled, noninferiority study. Patients (N=1,071; mean age, 62.6 years; 48.5% male; 89.7% white) with moderate-to-severe COPD on stable COPD therapy received FFIS (20 µg; n=541) or placebo (n=530) twice daily. The primary end point was the combined incidence of respiratory death, first COPD-related ER visit, or first COPD exacerbation-related hospitalization during 1 year post randomization. Noninferiority to placebo was concluded if the two-sided 90% CI of the HR of FFIS to placebo was <1.5. Secondary end points included spirometry. RESULTS: The planned 1-year treatment period was completed by 520 patients; 551 discontinued prematurely (FFIS: 45.7%; placebo: 57.4%). The median treatment duration was approximately 10 and 7 months for FFIS and placebo, respectively. Among 1,071 randomized patients, 121 had ≥1 primary event (FFIS: 11.8%; placebo: 10.8%). The estimated HR of a primary event with FFIS vs placebo was 0.965 (90% CI: 0.711, 1.308), demonstrating that FFIS was noninferior to placebo. No respiratory deaths were observed in the FFIS group. Adverse events were similar for FFIS vs placebo (patients with ≥1 treatment-emergent adverse events: 374 [69.1%] vs 369 [69.6%], respectively). Compared with placebo, FFIS demonstrated statistically greater improvements from baseline in trough FEV1, FVC, percent predicted FEV1, and patient-reported outcomes (Transition Dyspnea Index). CONCLUSIONS: Nebulized FFIS was noninferior to placebo with respect to safety in patients with moderate-to-severe COPD. Additionally, fewer treatment withdrawals and larger lung function improvements were observed with FFIS compared with placebo when added to other maintenance COPD therapies.

Onset of Action of the Fixed Combination Intranasal Azelastine-Fluticasone Propionate in an Allergen Exposure Chamber.

BACKGROUND: A fixed-dose combination of intranasal azelastine hydrochloride and fluticasone propionate (MP-AzeFlu) is the most effective treatment of allergic rhinitis, but its onset of action requires further investigation. OBJECTIVE: To compare the onset of action of MP-AzeFlu with the free combination of oral loratadine (LORA) and intranasal fluticasone propionate (INFP). METHODS: In this single-center, randomized, placebo-controlled, double-blind, double-dummy, 3-period crossover trial, allergic rhinitis symptoms were induced in asymptomatic patients by ragweed pollen challenge in an allergen environmental exposure chamber. Patients received single-dose MP-AzeFlu, LORA/INFP, or placebo and were monitored for 4 hours. The primary outcome was onset of action measured by total nasal symptom score (TNSS). Secondary measures were total ocular symptom score (TOSS), total score of the 7 nasal and ocular symptoms (T7SS), and the global visual analog scale (VAS). RESULTS: The full analysis set included 82 patients, of which 78 completed all treatments. TNSS was significantly reduced versus placebo from 5 minutes for MP-AzeFlu and 150 minutes for LORA/INFP onward (both P < .05) till the end of assessment (0-4 hours). MP-AzeFlu reduced TNSS to a greater extent at each time point from 5 to 90 minutes (P < .05) and over the entire assessment interval (P ≤ .005) versus LORA/INFP or placebo. No statistically significant difference between LORA/INFP and placebo was observed over the assessment interval (P = .182). The onset of action of MP-AzeFlu assessed by TOSS, T7SS, and VAS was 10 minutes, 2 hours earlier than with LORA/INFP. CONCLUSION: MP-AzeFlu had a more rapid onset of action (5 minutes) and was more effective than LORA/INFP.