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Introduction Fixed-dose long-acting beta2-agonist (LABA)/inhaled corticosteroid (ICS) combinations and add-on therapies as needed are the mainstay for maintenance therapy in asthma. However, more than 40% of patients have an inadequately controlled disease. The development of triple fixed-dose combinations consisting of long-acting muscarinic antagonist (LAMA)/LABA/ICS has paved the way for a new approach to reach therapeutic goals of an optimal control of symptoms and an effective prevention of future exacerbations. Areas covered A search was conducted on PubMed (MEDLINE), using the MeSH terms [asthma] + [indacaterol] + [glycopyrronium] +[mometasone furoate] + [treatment], until October 2021. Original data from clinical trials, prospective and retrospective studies and reviews were selected. Clinical studies with IND/MF/GLY (Enerzair Breezhaler) are summarized, and its place in current asthma therapy is examined. Expert opinion Triple therapy has been shown to be an effective and safe therapeutic option for asthma patients who remain uncontrolled despite ICS/LABA combination. The recently approved single-inhaler indacaterol/glycopyrronium/mometasone fixed dose combination has demonstrated to significantly reduce exacerbations, improve FEV1, symptoms and quality of life compared to ICS/LABA, including, salmeterol/fluticasone combination. Moreover, once-daily dosing may improve adherence.

Background: Chronic rhinosinusitis with nasal polyps affects approximately 2–4% of the general population, and long-term use of systemic corticosteroids is associated with adverse effects. The aim of this study was to assess the efficacy and safety of mepolizumab in adults with recurrent, refractory severe bilateral chronic rhinosinusitis with nasal polyps. Methods: SYNAPSE was a randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial done at 93 centres, mainly hospitals, in 11 countries. Eligible patients were aged 18 years or older with recurrent, refractory, severe, bilateral nasal polyp symptoms (nasal obstruction symptom visual analogue scale [VAS] score of >5), were eligible for repeat nasal surgery (overall symptoms VAS score >7 and endoscopic nasal polyps score of ≥5, with a minimum score of 2 in each nasal cavity) despite standard of care treatment, and had to have at least one nasal surgery in the past 10 years. Patients were randomly assigned (1:1), using permuted block design, to receive either 100 mg mepolizumab subcutaneously or placebo once every 4 weeks, in addition to standard of care (mometasone furoate intranasal spray for at least 8 weeks before screening and during the study, saline nasal irrigations, systemic corticosteroids or antibiotics, or both), as required, for 52 weeks. Site staff, the central study team, and patients were masked to study treatment and absolute blood eosinophil counts. The coprimary endpoints were change from baseline in total endoscopic nasal polyp score at week 52 and in mean nasal obstruction VAS score during weeks 49–52, assessed in the intention-to-treat population (ITT). This study is registered with ClinicalTrials.gov, NCT03085797. Findings: From May 25, 2017, to Dec 12, 2018, 854 patients were screened for eligibility. 414 patients were randomly assigned with 407 included in the ITT population; 206 received mepolizumab and 201 received placebo. Total endoscopic nasal polyp score significantly improved at week 52 from baseline with mepolizumab versus placebo (adjusted difference in medians −0·73, 95% CI −1·11 to −0·34; p

A stability-indicating validated high-performance thin-layer chromatography method was performed for the determination of mometasone furoate (MM) and salicylic acid (SLY), simultaneously within the concentration range of 0.1–1.6 μg/band for MM and 0.4–5 μg/band for SLY. This method was developed to assay the investigated drugs in the presence of their degradation products by alkaline, acidic, neutral, photolytic, and oxidative degradation. Separation was achieved using dual wavelength system, 250 nm for MM and 300 nm for SLY, with mobile phase composed of chloroform–ethanol (9:1, %v/v) and stationary phase of aluminum plates pre-coated with silica gel 60 F245. The proposed method is well used for the assay and separation of MM and SLY in pure form and Elicasal® ointment. The developed method has many advantages such as being rapid, selective and inexpensive. Such advantages promote the suggested method for the high throughput assay of MM and SLY mixture, in pure form and topical preparation. The developed method was validated according to the International Council for Harmonisation guidelines, in terms of linearity, limits of detection and quantification, precision, accuracy, robustness, and specificity. Assessment of greenness has been performed depending on analytical eco-scale approach.

Background Medically refractory chronic rhinosinusitis (CRS) is often treated with functional endoscopic sinus surgery (FESS) and high-volume steroid nasal irrigation. While budesonide is the most common steroid irrigation for this indication, mometasone has a superior pharmacokinetic profile, which may allow dose escalation. The safety and efficacy of mometasone at higher concentrations than previously used in treating CRS have not been explored. Methods Patients were recruited from a tertiary level clinic between June 2018 and December 2019. Inclusion criteria included adults (>18 years); CRS diagnosis; previous FESS; pre-treatment morning cortisol within normal range; minimum of twice daily high-volume sinonasal mometasone irrigations (total dose of 4 mg) for 12 weeks; and post-treatment morning cortisol measured within 2 weeks following the study period. Patients with potential for endogenous or exogenous disruption of the HPA axis were excluded. Results 14 patients were enrolled in this prospective cohort study. In all but one patient, pre- and post-treatment morning cortisol levels were not significantly different and were within normal limits (6.7-25.4 μg/dL). Following an uninterrupted 12-week treatment course, no evidence of HPA axis suppression was found (P = 0.915). The single patient who was found to have a low (1.3 μg/dL) post-treatment morning serum cortisol level reportedly received an intraarticular steroid shot several days prior to the blood draw. She remained asymptomatic and her rechecked serum cortisol was within normal limits at 12.3 μg/dL. Conclusions High-volume 2 mg twice daily sinonasal mometasone irrigations did not cause HPA axis suppression in a representative sample of patients with refractory CRS post-FESS with normal baseline cortisol levels.

Background Intranasal corticosteroid sprays (INCSs) used to treat chronic rhinosinusitis are suboptimal due to limited penetration into the middle meatus, rapid clearance, and poor patient compliance. A bioresorbable drug matrix, developed with the XTreoTM drug delivery platform, may overcome the limitations of INCS by providing continuous dosing over several months. Objective To evaluate the in vitro drug release and in vivo pharmacokinetics of novel mometasone furoate (MF) matrices in a rabbit dorsal maxillary osteotomy model. Methods XTreoTM matrices were formulated to consistently elute MF for up to 6 months. Matrices were surgically placed bilaterally into the maxillary sinuses of New Zealand White (NZW) rabbits. Tissue and plasma MF concentrations were measured to assess the in vivo drug delivery. The in vivo and in vitro drug release kinetics of the matrices were quantified and compared to those of rabbits receiving daily Nasonex® MF nasal sprays. Results XTreoTM matrices self-expanded upon deployment to conform to the irregular geometry of the maxillary sinus cavities in the NZW rabbits. Sustained release of MF was demonstrated in vitro and in vivo for 2 MF matrices of distinct release durations and an in vitro–in vivo correlation was established. Therapeutic levels of MF in local tissues were measured throughout the intended dosing durations. In contrast to the variable peaks and troughs of daily nasal sprays, sustained dosing via a single administration of MF matrices was confirmed by quantifiable plasma MF concentrations over the intended dosing duration. Conclusion The XTreoTM MF matrices provided targeted and efficient dosing to local sinus tissues that was superior to INCS. Sustained drug release was confirmed both in vitro and in vivo. The novel XTreoTM technology may provide precisely tuned, long-lasting drug delivery to sinus tissues with a single treatment.

Mometasone furoate (MF) is a glucocorticoid prodrug that faces the problem of poor aqueous solubility. Nanoemulsion-based topical gel of MF was formulated to enhance its solubility and potential of treating skin conditions. The selection of oil, surfactant and co-surfactant was done based on their solubility with the drug. The nanoemulsion was prepared using rose oil as the oil phase. Tween 80 and Transcutol P were used as surfactant and co-surfactant and they were blended in different ratios (1:0, 1:1, 2:1 and 3:1 w/w). The pseudo ternary diagrams were developed using these excipients and formulations exhibiting considerable nanoemulsion region were selected. The formulations were optimized by using Design Expert software for the globule size and cumulative percent release. The nanoemulsion formulations were characterized for in vitro release and stability study. The optimized nanoemulsions consisting of 2 % w/w oil, 30 % w/w Smix (Surfactant: Co-surfactant) and 67.9 % w/w water were consolidated into Carbopol 940 gelling agent to prepare three nanoemulsion-based gel formulations or nanoemulgels (NEG1-NEG3). Nanoemulgels were evaluated for their stability and ex vivo permeation of MF. The outcomes suggested that skin permeation of MF from all the nanoemulgel formulations was significantly enhanced as compared to the marketed mometasone furoate topical formulation.

Objective:. To retrospectively evaluate efficacy and safety of 0.05% halometasone/1% triclosan cream (Hal/TCS) in treating truncal vitiligo of children and adolescents. Methods:. We retrospectively reviewed the records of children and adolescents with truncal vitiligo treated only with topical Hal/TCS twice daily or only with topical 0.1% mometasone furoate cream (mometasone) twice daily for at least 3 months, and collected relevant data. Efficacy outcomes included patients’ mean repigmentation score after 1- and 3-month treatment calculated based on patients’ repigmentation percentage, and effective rate (percentage of patients with ≥50% repigmentation). Subgroup analyses of patients’ mean repigmentation score based on their age, vitiligo stage, and duration were conducted. Rate of adverse events were calculated. Results:. One hundred and twenty-two eligible patients were included, among them, 63 and 59 patients were in the Hal/TCS group and the mometasone group, respectively. After 3 months of treatment, the Hal/TCS group had significantly higher mean repigmentation score and effective rate than the mometasone group (53.49 ± 28.33 vs. 41.46 ± 27.16, P = 0.02; 53.97% vs. 35.59%, P = 0.04, respectively). Patients with shorter disease duration (≤12 months) and patients with progressive vitiligo responded significantly better to the Hal/TCS treatment than patients with longer disease duration and patients with stable vitiligo, respectively. Both treatments were well tolerated and the two treatment groups had comparable rates of adverse events. Conclusions:. Short-term Hal/TCS treatment was effective, well-tolerated, and safe in treating vitiligo in the trunk of children and adolescents.

Purpose: The purpose of this study is to develop a new PLGA based formulation for microspheres, which aims to release mometasone furoate for one month, so as to improve compliance. Methods: The microspheres containing mometasone furoate were prepared by oil in water emulsion and solvent evaporation. The microspheres were characterized by surface morphology, shape, size and encapsulation efficiency. The release in vitro was studied in 37°C phosphate buffer, and in vivo, pharmacodynamics and preliminary safety evaluation were conducted in male Sprague Dawley rats. Results: The morphology results showed that the microspheres have a smooth surface, spherical shape and an average diameter of 2.320-5.679μm. The encapsulation efficiency of the microspheres loaded with mometasone furoate was in the range of 53.1% to 95.2%, and the encapsulation efficiency of the microspheres could be greatly affected by the proportion of oil phase to the water phase and other formulation parameters. In vitro release kinetics revealed that drug release from microspheres was through non-Fick's diffusion and PLGA polymer erosion. Pharmacokinetic data showed that the initial release of microspheres was small and then sustained. The results of the pharmacodynamics study fully proved the long-term effectiveness of mometasone furoate microspheres. The results of in vivo safety evaluation showed that the preparation system possessed good in vivo safety. Conclusion: This study shows that the microspheres prepared in this study have sufficient ability to stable drug release at least for 35 days, with good efficacy and high safety. In addition, mometasone furoate can be used as a potential candidate drug for 35 days long-term injection.

Contact dermatitis is one the commonest dermatological condition which is managed by topical corticosteroids. Mid potent topical corticosteroids are commonly prescribed but there is no any comparative data between mometasone furoate and fluticasone propionate in the management of dermatitis.A real world retrospective study was conducted across India to compare the clinical assessment of mometasone 0.1% cream and fluticasone 0.005% cream in the management of contact dermatitis at 236 dermatology clinics.A data of 1106 patients were included in this analysis in which 598 were included in mometasone group while 508 in fluticasone group. At the end of 2 weeks, 216 patients (36.1%) in mometasone and 129 patients (25.4%) in fluticasone group achieved complete clearance of symptoms (pBoth, mometasone furoate and fluticasone propionate were effective and safe in treatment of eczema/dermatitis. But mometasone furoate had shown significantly better effectiveness as compared to fluticasone in all predisposing factors for the disease.

Background and Objective Clinical evidence suggests no clinically relevant pharmacokinetic interactions between indacaterol (IND), glycopyrronium (GLY) and mometasone furoate (MF). A population pharmacokinetic (popPK) analysis was conducted to identify structural models describing systemic pharmacokinetic profiles of IND, GLY and MF, and estimate the effect of covariates on their pharmacokinetics following inhalation as IND/GLY/MF. Methods Pharmacokinetic data from 698 patients with asthma were pooled from two Phase III studies that evaluated IND/MF medium- (150/160 µg) and high-dose (150/320 µg), IND/GLY/MF medium- (150/50/80 μg) and high-dose (150/50/160 μg), and a device bridging Phase II study with MF. One popPK model was developed each for IND, GLY and MF using a nonlinear mixed-effect modelling approach. Maximal and trough plasma concentrations were compared across formulations and studies, including data for IND/GLY from chronic obstructive pulmonary disease (COPD) patients. The effect of predefined covariates on the pharmacokinetics of components was evaluated using a full covariate modelling approach. Results The final pharmacokinetic models were two-compartment disposition models with first-order elimination and sequential zero-order/first-order absorption (IND), with bolus administration and first-order elimination (GLY), and with mixed zero-order/first-order absorption and first-order elimination (MF). All model parameters were estimated with good precision (% relative standard error: IND and MF ≤25%; GLY

Indacaterol/glycopyrronium/mometasone (Enerzair® Breezhaler®) is a fixed-dose combination of the long-acting β2 agonist (LABA) indacaterol, the long-acting muscarinic antagonist (LAMA) glycopyrronium and the inhaled corticosteroid (ICS) mometasone furoate (hereafter referred to as mometasone) delivered via a capsule-based dry-powder inhaler. It is approved in the EU for use as maintenance treatment in adult patients with inadequately controlled asthma who had experienced one or more exacerbations in the previous year. The approval also includes an optional digital companion (sensor and app) that provides data on the patient's use of the inhaler. In the 52-week IRIDIUM trial in patients with inadequately controlled asthma, indacaterol/glycopyrronium/mometasone improved lung function to a greater extent than LABA/ICS combinations (i.e. indacaterol/mometasone and fluticasone propionate/salmeterol), but superiority in Asthma Control Questionnaire 7 score was not shown. In the 24-week ARGON trial, indacaterol/glycopyrronium/mometasone via a single inhaler was non-inferior to fluticasone propionate/salmeterol + tiotropium via two inhalers with regard to Asthma Quality of Life Questionnaire score. Indacaterol/glycopyrronium/mometasone was generally well tolerated, and the most common adverse events were respiratory in nature. In conclusion, combination therapy with indacaterol/glycopyrronium/mometasone represents a valuable option for the maintenance treatment of asthma, with the convenience of once-daily administration via a single inhaler.

Objective To assess the effects and adverse events of preparation Sinulan forte® containing extracts of five medicinal plants in comparison to mometasone furoate nasal spray (MFNS) in therapy of acute postviral rhinosinusitis (APRS). Methods We included 46 APRS patients in this prospective investigation and randomized to two groups. The patients in group 1 (n=23) received MFNS 200 μg two times/day for ten days, and patients in group 2 (n=23) received Sinulan forte®, tablets 225 mg per os, two times/day also for ten days. We evaluated the total symptom score (TSS), the separate scores for individual symptoms (nasal congestion, rhinorrhea, postnasal discharge, facial pain, impaired sense of smell), the quality-of-life outcome, and the findings from nasal endoscopy (edema of the nasal mucosa, nasal secretion) prior and after the therapy. Results Significantly lower absolute post-treatment scores and better relative improvement were identified for TSS, nasal congestion, facial pain, loss of the sense of smell, edema of the mucosa and nasal secretion in patients receiving herbal preparation (group 2). However, lower absolute post-treatment score and better relative improvement were found for rhinorrhea and postnasal drip in group 1. Clinically important differences were found regarding the TSS and endoscopic findings, with no adverse effects in group 2, but in group 1 two patients had mild nasal bleeding and two had sensation of dryness in the nasal mucosa. Conclusion Herbal product Sinulan forte® can be a safe and effective treatment for APRS. Our results suggest no adverse events of this herbal preparation in comparison to intranasal corticosteroid spray therapy.

Achieving the control of bronchial asthma (BA) in real clinical practice remains an unresolved problem, despite the expansion of therapeutic options in this area. Guidelines about when and for whom should a particular treatment be used continue to develop. Increasing of inhaled corticosteroid dose (ICS) in combination with a long-acting β2-agonist (LABA) does not always lead to the desired result, although a combined LABA-ICS inhaler could improve the course of asthma and increase adherence. The addition of tiotropium bromide to LABA-ICS requires the use of two inhalers. The targeted biological therapy is associated with the complexity of phenotyping and is possible only in specialized medical centers. Mometasone furoate, indacaterol acetate, and glycopyrronium bromide in fixed doses were combined in Breezhaler® inhaler for asthma maintenance therapy once per day. This way of treatment helps to realize full potential of maintenance inhalation therapy of bronchial asthma and to simplify the achievement of control over the disease in routine clinical practice.

Introduction: A very limited option of inhaled corticosteroids (ICSs) is approved for pediatric use in China because in children the use of ICSs for long periods is associated with dose-dependent growth reduction. Due to the lack of consensus on which is the best ICS-based treatment option to manage mild persistent asthma in children, the present study was performed to evaluate the efficacy and safety of budesonide (BUD)-based therapy vis-à-vis mometasone-based therapy in children with mild persistent asthma. Methods: A single-center, retrospective study was conducted in asthmatic children aged between 6 and 11 years. BUD and mometasone furoate (MF) were administered as per the approved dosing regimen using pressurized metered-dose inhalers via oral inhalation route for a period of 12 weeks. The study outcome was assessed in terms of the forced expiratory volume in 1 s (FEV1), symptom scores, and nonoccurrence of side effects. Results: Among the 77 asthmatic children, 71 completed the study treatment and were used in carrying out the analysis. The improvement of spirometric parameters like FEV1, Tiffeneau-Pinelli index (FEV1/forced vital capacity [FVC]), and peak expiratory flow (PEF) values observed in the MF cohort was significantly greater than those of the BUD cohort (p < 0.05 for all). An increase of approximately 12%/child was observed for FEV1/FVC ratios for the BUD cohort and MF cohorts. After the 12-week study, the PEFm and PEFe values increased to about 50 L/min/child for the BUD cohort and about 98 L/min/child for the MF cohort. During the study, no asthma exacerbation event was observed in the MF cohort, whereas 1 child in the BUD cohort had asthma exacerbation in week 4. The use of rescue medication during the study was required for 16.2 and 6% of children, respectively, for BUD and MF cohorts. Owing to low dosing frequency, MF could provide a better treatment approach than BUD due to improved patient compliance. Conclusions: Although both drugs showed improvement in the quality of life of asthmatic children with manageable treatment-emergent adverse effects, the improvement was augmented in MF-treated children. Level of Evidence: The level of evidence was III. Technical Efficacy Stage: The technical efficacy stage was 4.

Skin biomarkers for disease severity and treatment response in atopic dermatitis (AD) are needed. Biopsies cause scarring and tape stripping represents an alternative minimally invasive method for stratum corneum sampling. In this study, we examined the gene expression of cytokines in skin biopsies and cytokines in stratum corneum tape strips collected from adults with AD. We collected punch biopsies and tape strips from healthy controls (n = 6) and subjects with AD (n = 12) at baseline and after 2 weeks of topical treatment with mometasone furoate 0.1% cream. We found that IFN-γ, IL-13, and IL-10 mRNA (biopsies) and IL-1β protein expression levels (tape strips) were significantly increased in lesional AD skin compared to healthy control skin. Treatment with topical corticosteroid led to a significant decrease in mRNA levels for IL-13 and IL-4R but no significant differences in cytokine protein levels measured in tape strips. Finally, we found no significant correlations between cytokine levels in tape strips and mRNA levels in skin biopsies.

OBJECTIVE The aim: Of research was to evaluate the effectiveness of bacteriophage in patients with acute rhinosinusitis in respect of technique of delayed prescribing of antibiotics. PATIENTS AND METHODS Materials and methods: There were examined 155 patients who were given irrigation therapy with isotonic solution of sea water 4 times a day and mometasone furoate of 100 mg twice a day for 10 days. The patients of intervention group (n - 80) were additionally prescribed the polyvalent bacteriophage endonasally, in drops of 2-10 ml 3 times a day. RESULTS Results: The patients in the control group were observed the decrease in intensity of rhinorrhea, nasal congestion and post-nasal drip on the third day of supervision (p < 0.05), the reduction in bacterial load with Staphylococcus aureus, S. pneumoniae, Haemophilus influenza and M. Catarrhalis (р

Stability indicating reversed phase-HPLC method for simultaneous estimation of mometasone furoate (MAF) and formoterol fumarate (FFD) in metered dose inhalation aerosol (MDI) dosage formulation has been developed and discussed in the present work. The chromatographic separation was achieved using Hypersil ODS column (250 mm × 4.6 mm, 3 μm) using an isocratic separation mode at a flow rate of 1.2 mL/min, column temperature of 50 ºC. The system operates with a mobile phase comprising of solution-A (buffer): Solution-B (acetonitrile) mixed in the ratio of 70:30 %v/v at a UV detection wavelength of 214 nm. Retention times of mometasone furoate and formoterol fumarate found to be about 3 min and 7 min, respectively. All possible degradation products of both compounds were monitored at 214 nm and spectral purity along with % mass balance is assessed using PDA detector. Both analyte were subjected to force degradation studies, found all degradants were resolved from analyte peaks and also other process-related impurities. The proposed method is validated for specificity, linearity, accuracy, precision and robustness as per ICH guidelines and found to be adequate. Method stood to be robust with variation in column temperature, flow rate, pH of buffer and organic content in mobile phase.

Background. The chronic and recurrent nature of seborrheic dermatitis, its wide prevalence and multifactorial etiopathogenesis require a comparison of the effectiveness of different treatment strategies. Aim. In a randomized controlled trial to evaluate the effectiveness of standard and intermittent therapy with topical corticosteroids and activated zinc pyrithione (Skin-cap cream) in reducing the severity of clinical manifestations, the duration of remission of the disease, and compliance with treatment. Methods. The effectiveness of external therapy in patients with seborrheic dermatitis of the face and scalp was studied. All the examined patients had at least two episodes of exacerbation per year. Doctor's prescription Mometasone furoate cream 0.1% 1 time/day externally for 14 days, activated zinc pyrithione (Skin-cap cream) 2 times/day externally for 14 days, further 1 time a day 2 times a week for 14 days. Results. There was a comparable clinical effectiveness of antiinflammatory therapy in the short term with more stable results of intermittent therapy with the use of (Skin-cap cream) in the long term. Conclusions. Usage of activated zinc pyrithione (Skin-cap cream) according to the intermittent scheme in the treatment of seborrheic dermatitis of the face with the transition to the scalp is associated with long-term results. Safety of medicine allows to use it pro re nata by patients, e.g., in case of increased stress levels, diet incompliance, with no risks of adverse events, specific to topical corticosteroids, those increases treatment compliance.

Rhinitis can be of various etiologies. More often it is an infectious process (bacterial, viral) or clinical manifestations of an immediate allergic reaction. Other factors that provoke the development of rhinitis, for example, irritating substances, a number of drugs, hormonal imbalance, neurovegetative dysfunction, viruses are known. Doctors of various specialties are familiar with allergic rhinitis (AR) in their practice. In a number of cases there can be some difficulties in the differential diagnosis of rhinitis, the correct diagnosis and the appointment of adequate therapy. The COVID-19 epidemic (“coronavirus disease 2019”) has already been imprinted in the global history as an emergency of international importance. Scientific medical communities continue to study the characteristics of this epidemic, which is regarded by WHO as a pandemic. In a short period (from January 2020), there has been accumulated enough information about the etiology, features of the clinical manifestations of this disease, diagnostic methods have been developed, and clinical approaches and treatment regimens continue to be developed. The pandemic coincided with successive pollen seasons of trees, grasses and weeds. At the beginning of the pollen season, doctors were concerned about the possible difficulty in differential diagnosis of allergic rhinitis, manifestations of coronavirus and other viral infections. In the process of monitoring patients, more and more data has been accumulated, indicating the features of the clinical characteristics of COVID-19, influenza, acute respiratory infections, seasonal allergic rhinitis (rhinoconjunctivitis). Undoubtedly, information is still being accumulating and enriching day by day. AR is not only the most common form of rhinitis, but one of the most common diseases in children and adults. It is known about the pronounced negative effect of AR symptoms on the patient’s quality of life: normal daily activity, cognitive functions, mood, sleep. The severity of AR symptoms varies from minimal clinical manifestations to severe. Therapy should be directed towards the general control of AR symptoms. Over the past decades, the concept of phenotyping (definition of a disease by its clinical manifestations) and endotyping (based on the pathobiological mechanisms of the disease) has been developed. The belonging of AR in a particular patient to a certain phenotype plays a key role in choosing the most effective therapy and requires a personalized approach to treatment. The article provides frequently asked questions regarding AR treatment during the COVID-19 pandemic. The role of intranasal corticosteroids (InHCS), which are the most effective drugs in AR therapy, is discussed, due to their pronounced anti-inflammatory effect and influence on all stages of the pathogenesis of the disease. Mometasone furoate nasal spray has the widest indications among all InHCS drugs registered in our country.

Though glucocorticoids are widely used in dermatological practice, some patients with hand eczema may have resistance to glucocorticoids, even when they are taken in heavy doses. Glucocorticoids mediate their actions through glucocorticoid receptors. Polymorphism of the glucocorticoid receptor gene (NR3C1) can inhibit the cellular response to glucocorticoids and lead to reduced response to the therapy. Some cytokines can affect the production of various glucocorticoid receptor subunits, modulating the cell response to glucocorticoids. However, there is still need in detailed study of pathogenetic mechanisms and the detection of highly specific predictors of glucocorticoid resistance. The aim of this work was to investigate the possible relation between glucocorticoid resistance in patients with hand eczema, rs41423247 SNP, and blood concentration of interleukin-17A and interleukin-2. The venous blood of 143 patients with hand eczema (42% of women and 58% of men) mean age 42.2 ± 11.1 years was taken for the study. During the patients examination the data on age, sex, body mass index (kg/m2), body mass index ≥ 25 (kg/m2(%)), the habit of smoking, concemtration of immunoglobulin E (iu/ml), interleukin-17A (pg/ml) and interleukin-2 (pg/ml) were obtained. The еczema аrea and severity index was assessed in each subject before the therapy and in two weeks since the therapy started. According to index value, all the patients were divided into three subgroups: mild eczema, moderate eczema, and severe eczema. Patients with mild and moderate eczema were prescribed to apply topical glucocorticoid 0.1% mometasone furoate cream twice a day for 2 weeks. The patients with severe hand eczema were prescribed to receive additional systemic corticosteroid, a solution of dexamethasone by intramuscular injection in a dose of 8 mg / day, then 4 mg / day for another 2 days. BclI SNP (rs41423247) of the glucocorticoid receptor gene (NR3C1) was determined using PCR-RFLP method. The quantitative variables were tested for normal distribution by the Shapiro-Wilk test. The comparisons of the means between the two subgroups were performed by Student's t-test for independent samples. The comparison of the frequencies distribution in the subgroups was calculated by using the Pearson test. The P value < 0.05 was considered as significant. Thus, the obtained results revealed that insensitivity to glucocorticoids in patients with hand eczema is related to NR3C1 gene Bcl-1 polymorphism, eczema severity and plasma level of interleukin-17, interleukin-2. The plasma content of interleukin-17 and interleukin-2 in patients with glucocorticoid resistance was significantly higher compared to hormone-sensitive subjects. There were significantly more people with the C/G- and G/G genotypes in the group that did not have a clinical response to therapy.

Based on the latest new international literature data, the article considers the possibilities of fixed combinations of long-acting β2-agonist, long-acting muscarinic antagonist and inhaled corticosteroids in achieving the control of bronchial asthma (BA). Clinical advantages for a fixed combination of indacaterol, glycopyrronium and mometasone furoate one dosing regimen in the therapy of BA are presented based on the results of recently completed randomized clinical trials IRIDIUM and ARGON.

Summary Background Fixed-dose combinations (FDCs) of inhaled corticosteroids (ICS) and long-acting β2-adrenoceptor agonists (LABA) are considered safe and efficacious in asthma management. Most available FDCs require twice-daily dosing to achieve optimum therapeutic effect. The objective of the PALLADIUM study was to assess the efficacy and safety of once-daily FDC of mometasone furoate plus indacaterol acetate (MF–IND) versus mometasone furoate (MF) monotherapy in patients with inadequately controlled asthma. Methods This 52-week, double-blind, triple-dummy, parallel-group, phase 3 study recruited patients from 316 centres across 24 countries. Patients aged 12 to 75 years with a documented diagnosis of asthma for at least 1 year, percentage of predicted FEV1 of 50–85%, and an Asthma Control Questionnaire 7 score of at least 1·5 despite treatment with medium-dose or high-dose ICS or low-dose ICS plus LABA were included. A history of asthma exacerbations was not a study requirement. Participants were randomily assigned (1:1:1:1:1) via interactive response technology to receive one of the following treatments for 52 weeks: high-dose MF–IND (320 μg, 150 μg) or medium-dose MF–IND (160 μg, 150 μg) once daily via Breezhaler; high-dose MF (800 μg [400 μg twice daily]) or medium-dose MF (400 μg once daily) via Twisthaler; or high-dose fluticasone propionate–salmeterol xinafoate (FLU–SAL; 500 μg, 50 μg) twice daily via Diskus. Participants received placebo via inhalation through the Breezhaler, Twisthaler, or Diskus devices in the mornings and evenings, as appropriate. The primary endpoint was improvement in trough FEV1 with high-dose and medium-dose MF–IND versus respective MF doses from baseline at 26 weeks, analysed in the full analysis set by means of a mixed model for repeated measures. High-dose MF–IND once daily was compared with high-dose FLU–SAL twice daily for non-inferiority on improving trough FEV1 at week 26 with a margin of −90 mL using mixed model for repeated measures as one of the secondary endpoints. Safety was assessed in all patients who had received at least one dose of study drug. This study is registered with ClinicalTrials.gov , NCT02554786 , and is completed. Findings Between Dec 29, 2015, and May 4, 2018, 2216 patients were randomly assigned (high-dose MF–IND, n=445; medium-dose MF–IND, n=439; high-dose MF, n=442; medium-dose MF, n=444; high-dose FLU–SAL, n=446), of which 1973 (89·0%) completed the study treatment and 234 (10·6%) prematurely discontinued study treatment. High-dose MF–IND (treatment difference [Δ] 132 mL [95% CI 88 to 176]; p Interpretation Once-daily FDC of ICS and LABA (MF−IND) significantly improved lung function over ICS monotherapy (MF) at week 26; high-dose MF–IND was non-inferior to twice-daily combination of ICS and LABA (high-dose FLU–SAL) for improvement in trough FEV1. The combination of MF–IND provides a novel once-daily dry powder option for asthma control. Funding Novartis Pharmaceuticals.

Background: Patients with asthma who are inadequately controlled on inhaled corticosteroid–long-acting β2-adrenoceptor agonist (ICS–LABA) combinations might benefit from the addition of a long-acting muscarinic receptor antagonist. The aim of the IRIDIUM study was to assess the efficacy and safety of a once-daily, single-inhaler combination of mometasone furoate, indacaterol acetate, and glycopyrronium bromide (MF–IND–GLY) versus ICS–LABA in patients with inadequately controlled asthma. Methods: In this 52-week, double-blind, double-dummy, parallel-group, active-controlled phase 3 study, patients were recruited from 415 sites across 41 countries. Patients aged 18 to 75 years with symptomatic asthma despite treatment with medium-dose or high-dose ICS–LABA, at least one exacerbation in the previous year, and a percentage of predicted FEV1 of less than 80% were included. Enrolled patients were randomly assigned (1:1:1:1:1) via interactive response technology to receive medium-dose or high-dose MF–IND–GLY (80 μg, 150 μg, 50 μg; 160 μg, 150 μg, 50 μg) or MF–IND (160 μg, 150 μg; 320 μg, 150 μg) once daily via Breezhaler, or high-dose fluticasone–salmeterol (FLU–SAL; 500 μg, 50 μg) twice daily via Diskus. The primary outcome was change from baseline in trough FEV1 with MF–IND–GLY versus MF–IND at week 26 in patients in the full analysis set, analysed by means of a mixed model for repeated measures. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT02571777, and is completed. Findings: Between Dec 8, 2015, and Jun 14, 2019, 3092 of 4851 patients screened were randomly assigned (medium-dose MF–IND–GLY, n=620; high-dose MF–IND–GLY, n=619; medium-dose MF–IND, n=617; high-dose MF–IND, n=618; high-dose FLU–SAL, n=618). 2747 (88·8%) patients completed the 52-week treatment and 321 (10·4%) started but discontinued study treatment prematurely. Medium-dose MF–IND–GLY (treatment difference [Δ] 76 mL [95% CI 41–111]; p1 versus corresponding doses of MF–IND at week 26. Improvements in trough FEV1 were greater for both medium-dose MF–IND–GLY (99 mL [64–133]; p