Digitally monitored inhaled therapy: a 'smart' way to manage severe asthma?

INTRODUCTION: One of the fundamental challenges of managing patients with severe asthma is treatment adherence, particularly with inhaled corticosteroids. Adherence is difficult to measure objectively and poor adherence is associated with worse outcomes. In this study, assess the ability of a 'smart' inhaler to record adherence in severe asthma patients and measure the impact of this on asthma control. METHODS: Consecutive consenting patients meeting criteria for biologics had their existing high-dose ICS/LABA//LAMA combination inhaler/s switched to mometasone/indacaterol/glycopyrronium (114/46/136). Routine clinical data, including blood eosinophils, FeNO, and ACQ-6 scores were collected at baseline and at 4 wk. Adherence was then checked on the Propeller Health app, and good adherence was defined as >80% of prescribed usage. Participants were then followed-up at 12 months to record the proportion of patients who were initiated on biologics. RESULTS: 77 patients (mean [SD] age = 50.4 [15.7] years, 67.5% female [n = 52]) participated. 71 participants were able to use the device and 65% (n = 46) of these attained good asthma control and were not initiated on biologics at 12-month follow-up. Both groups demonstrated a significant reduction in ACQ6 score at follow-up (2.81 vs. 1.92, p < 0.001 and 3.05 vs. 2.60, p < 0.001, respectively), but there was no statistically significant difference in improvement between groups. Patients with optimal adherence also demonstrated a significant reduction in median FeNO at follow-up (47 ppb vs. 40 ppb, p = 0.003). CONCLUSIONS: In severe asthma patients, 'smart' inhalers may represent an effective management tool to improve adherence and asthma control, therefore avoiding the need for patients to commence biological therapies.

Highly sensitive liquid chromatography-mass spectrometry method for the quantitative analysis of mometasone furoate in human plasma: Method validation and application to clinical pharmacokinetic studies.

We report the development and the validation of a sensitive liquid chromatography-mass spectrometry (LC-MS/MS) method for mometasone furoate (MF) analysis in human plasma. Plasma samples were processed through liquid-liquid extraction and analyzed using LC-MS/MS operating in positive mode using multiple reaction monitoring of transitions m/z 520.9 â†’ 355.0 and m/z 525.8 â†’ 355.0 for MF and the internal standard (IS), respectively. Separation was achieved at 1.0 mL/min on a C18 column using a gradient elution of mobile phase of 0.05% ammonia in water (phase A) and acetonitrile (phase B). The assay range was 0.250-100 pg/mL and proved to be accurate and precise MF. Normalized recoveries were consistent and reproducible with a coefficient of variation (CV%) value of 6.0. The CV (%) of the IS normalized matrix factor was not observed in normal, lipemic, and hemolyzed plasmas. Dilutions of 1:10 were accurately quantified. A cycle of three freeze and thaw and stabilities at room temperature and on the autosampler were demonstrated. In addition, MF in the presence of indacaterol and glycopyrronium was proven to be stable at -70°C for at least 157 days. The present method was successfully applied to quantify MF in patients receiving MF, indacaterol, and glycopyrronium as a fixed-dose combination.

Efficacy of Mometasone Furoate Cream Sodium Alginate Skin Repair Mask in Atopic Dermatitis Treatment.

Objective: To observe the clinical effect of mometasone furoate cream sodium Alginate Skin Repair Mask in the treatment of atopic dermatitis (AD). By assessing the combined use of these two treatments, the study aims to address a gap in knowledge regarding the effectiveness and safety of adjuvant therapies for AD, particularly in the context of Alginate Skin Repair Mask. Methods: Eighty patients were enrolled, including 42 males and 38 females aged 20-47 years, with an average age of (32.52±5.57) years, from July 2021 to July 2022, and the patients were divided into a single group (n=40) and a combined group (n=40) by random number table method. The patients in the single group were treated with mometasone furoate cream alone, and the patients in the combination group were treated with Alginate Skin Repair Mask on the basis of the treatment of the patients in the single group. The outcome measurements included clinical treatment effect, condition change (SCORAD score), quality of life (DLQI score), adverse reactions and disease recurrence were compared between the two groups. Both groups received treatment for 1 month. After the treatment of the patients, they were followed up for a period of 3 months. Results: The total effective rate of the single group was 80.0% (32/40), and that of the combined group was 97.5% (39/40) (P < .05). After treatment, the skin lesion area score, skin lesion degree score, pruritus insomnia score, and SCORAD total score in the combined group were significantly lower than those in the single group (35.03±9.41 vs 44.03±12.04) (all P < .05). The DLQI score of the combined group after treatment was significantly lower than that of the single group (3.72±1.53 vs 6.98±2.16) (P < .05). The incidence of adverse reactions in the single group was 22.5% (9/40), and the disease recurrence rate was 32.5% (13/40), while the incidence of adverse reactions in the combination group was 2.5% (1/40). The disease recurrence rate was 7.5% (3/40), and the incidence of adverse reactions and disease recurrence rate in the combination group were significantly lower than those in the single group (7.314, 7.812). Conclusion: Mometasone furoate cream sodium Alginate Skin Repair Mask has an ideal clinical effect in the treatment of atopic dermatitis. Compared with single mometasone furoate cream, the combination of sodium Alginate Skin Repair Mask can further improve the patient's condition, improve the quality of life of the patient, and reduce the risk of adverse reactions and disease recurrence. The higher total effective rate in the combined group indicates that the addition of Alginate Skin Repair Mask to the treatment regimen resulted in improved outcomes for patients with atopic dermatitis (AD). This translates to better control of the disease, reduction in symptoms, and overall improvement in the patient's condition.  However, it is important for clinicians to be aware that the use of topical glucocorticoids like mometasone furoate cream can potentially lead to adverse reactions. Some documented adverse reactions associated with long-term use of topical glucocorticoids include acne-like eruption, telangiectasia (dilation of small blood vessels), and local skin atrophy. By addressing multiple aspects of AD management, including skin barrier repair, moisturization, and inflammation control, the combination of mometasone furoate cream and Alginate Skin Repair Mask provides a more comprehensive treatment approach. This comprehensive approach may contribute to the observed reduction in recurrence rate in the combination group compared to the single group, where only mometasone furoate cream was used.

Maximal medical treatment of adenoid hypertrophy: a prospective study of preschool children.

PURPOSE: This study aimed to examine the effectiveness of the combined maximal medical treatment for adenoid hypertrophy in preschool children. METHODS: Sixty-four children underwent one-year combined therapy with intranasal mometasone furoate, oral desloratadine, nasal saline irrigation, and bacteriotherapy. Additionally, decongestion drops were applied during scheduled breaks. RESULTS: Of the 64 treated children, 72% showed clinical improvement in adenoid symptoms while 28% did not improve and underwent surgery. These groups differed significantly in terms of the overall reduction in ailments after treatment (p < 0.001), infection rate (p < 0.001), catarrh severity (p < 0.001) and nasal patency (p < 0.001). Endoscopic examination confirmed that responders experienced, on average, a decrease of 8.4% in the adenoid/choana ratio and an improvement in mucosal coverage of the adenoid. These effects were not observed in the group of children whose parents opted for surgery after nine months of conservative treatment. CONCLUSIONS: The proposed new schema of long-term maximal medical treatment with the use of combined intermittent treatment of intranasal mometasone furoate and decongestion drops, oral desloratadine, nasal saline irrigation, and bacteriotherapy can be attempted in patients with adenoid hypertrophy symptoms, and responders may avoid the need for surgery. The applied treatment breaks resulted in a low number of therapeutic side effects.

Allergic Rhinitis: A Review.

Importance: Allergic rhinitis affects an estimated 15% of the US population (approximately 50 million individuals) and is associated with the presence of asthma, eczema, chronic or recurrent sinusitis, cough, and both tension and migraine headaches. Observations: Allergic rhinitis occurs when disruption of the epithelial barrier allows allergens to penetrate the mucosal epithelium of nasal passages, inducing a T-helper type 2 inflammatory response and production of allergen-specific IgE. Allergic rhinitis typically presents with symptoms of nasal congestion, rhinorrhea, postnasal drainage, sneezing, and itching of the eyes, nose, and throat. In an international study, the most common symptoms of allergic rhinitis were rhinorrhea (90.38%) and nasal congestion (94.23%). Patients with nonallergic rhinitis present primarily with nasal congestion and postnasal drainage frequently associated with sinus pressure, ear plugging, muffled sounds and pain, and eustachian tube dysfunction that is less responsive to nasal corticosteroids. Patients with seasonal allergic rhinitis typically have physical examination findings of edematous and pale turbinates. Patients with perennial allergic rhinitis typically have erythematous and inflamed turbinates with serous secretions that appear similar to other forms of chronic rhinitis at physical examination. Patients with nonallergic rhinitis have negative test results for specific IgE aeroallergens. Intermittent allergic rhinitis is defined as symptoms occurring less than 4 consecutive days/week or less than 4 consecutive weeks/year. Persistent allergic rhinitis is defined as symptoms occurring more often than 4 consecutive days/week and for more than 4 consecutive weeks/year. Patients with allergic rhinitis should avoid inciting allergens. In addition, first-line treatment for mild intermittent or mild persistent allergic rhinitis may include a second-generation H1 antihistamine (eg, cetirizine, fexofenadine, desloratadine, loratadine) or an intranasal antihistamine (eg, azelastine, olopatadine), whereas patients with persistent moderate to severe allergic rhinitis should be treated initially with an intranasal corticosteroid (eg, fluticasone, triamcinolone, budesonide, mometasone) either alone or in combination with an intranasal antihistamine. In contrast, first-line therapy for patients with nonallergic rhinitis consists of an intranasal antihistamine as monotherapy or in combination with an intranasal corticosteroid. Conclusions and Relevance: Allergic rhinitis is associated with symptoms of nasal congestion, sneezing, and itching of the eyes, nose, and throat. Patients with allergic rhinitis should be instructed to avoid inciting allergens. Therapies include second-generation H1 antihistamines (eg, cetirizine, fexofenadine, desloratadine, loratadine), intranasal antihistamines (eg, azelastine, olopatadine), and intranasal corticosteroids (eg, fluticasone, triamcinolone, budesonide, mometasone) and should be selected based on the severity and frequency of symptoms and patient preference.

Efficacy and safety of self-made WenyangJianpi-qushi Decoction combined with mometasone furoate cream in the treatment of atopic dermatitis of spleen deficiency and dampness accumulation type.

Introduction: This work was to explore the efficacy and safety of self-made WenyangJianpi-qushi Decoction plus mometasone furoate cream in atopic dermatitis (AD) of spleen deficiency and dampness accumulation type. Material and method: 120 patients with this kind of atopic dermatitis were grouped: The Observation group (disease health education + basic treatment + mometasone furoate cream + self-made Decoction) and The Control group (disease health education + basic treatment + mometasone furoate cream), 60 cases in each group. The SCORAD score, serum IgE level, peripheral blood eosinophils, adverse events, recurrence rate, and total effective rate after treatment were observed.Result: Through treatment, SCORAD score of the observation group (29.96 ± 2.88) was lower as against controls (36.04 ± 3.12), p < 0.05. Through treatment, the peripheral blood eosinophil count in the observation group was (311.26 ± 50.19) 106/L, which was lower than (582.71 ± 54.75) 106/L in controls; the serum lgE of the observation group was (712.44 ± 93.32) IU/mL, which was lower than the controls (890.12 ± 81.25) IU/mL, p < 0.05. The Observation group (56/60, 93.33%) demonstrated superior total effective rate to the controls (34/60, 56.67%); The recurrence rate of the observation group was 4/60 (6.67%), which was lower than the controls 16/60 (26.67%), p < 0.05.Conclusion: Self-made WenyangJianpi-qushi Decoction plus mometasone furoate cream to treat atopic dermatitis of spleen deficiency and dampness accumulation type has significant efficacy and good safety.

Efficacy of montelukast for adenoid hypertrophy in paediatrics: A systematic review and meta-analysis.

INTRODUCTION: Leukotrienes play a significant role in the pathogenesis of adenoid hypertrophy (A.H.). Therefore, we aimed to analyse the role of montelukast, a leukotriene receptor antagonist, alone or in combination with mometasone, a potent local intranasal steroid, for the treatment of A.H. METHODS: Participants were children with A.H. were treated with montelukast alone or montelukast and mometasone furoate. The main outcome measures were effect of montelukast on clinical symptoms of A.H. A literature review was conducted using online search engines, Cochrane Library, PubMed, Web of Science and Scopus, for randomized clinical trials assessing children with A.H. treated with montelukast alone or montelukast and mometasone furoate. Seven randomized clinical trials (RCTs) were included with 742 children. RESULTS: Our study reveals that montelukast alone or in combination with intranasal mometasone furoate significantly improves clinical symptoms of adenoid hypertrophy such as snoring, sleeping disturbance, mouth breathing and A/N ratio. Montelukast was superior to placebo in decreasing snoring (SMD = -1.00, 95% CI [-1.52, -0.49]), sleep discomfort (SMD = -1.26, 95% CI [-1.60, -0.93]), A/N ratio (MD = -0.11, 95% CI [-0.14, -0.09]) and mouth breathing (SMD = -1.36, 95% CI [-1.70, -1.02]). No difference was detected between montelukast and mometasone versus mometasone alone in snoring (SMD = -0.21, 95%CI [-0.69, 0.27]); however, the combination group was superior to the mometasone alone in mouth breathing (SMD = -0.46, 95% CI [-0.73, -0.19]). CONCLUSIONS: The limitation of studies included a small sample size, with an overall low to medium quality. Thus, further larger, higher-quality RCTs are recommended to provide more substantial evidence.

[Clinical and pathological analysis of 345 cases of vulvar lichen sclerosus and a preliminary study on the frequency of maintenance treatment].

Objective: To analyze and summarize the clinical and pathological characteristics, management, and efficacy of patients with vulvar lichen sclerosus (VLS) through a single center large sample study, and preliminarily to explore the frequency of maintenance treatment medication for VLS. Methods: The clinical data of VLS patients in Obstetrics and Gynecology Hospital of Fudan University from 2018 to 2021 were retrospectively collected. The clinicopathological characteristics (patients' age, course of disease, complicated disease history, family history, symptoms, signs and pathology), treatment and effects were retrospectively analyzed. The patients in the maintenance treatment stage were followed up regularly to explore the minimum frequency of individual medication to maintain the stability of the disease. Results: (1) General situation: a total of 345 patients with VLS were included in this study. The average age was (50.4±14.7) years (ranged from 8 to 84 years old), prevalence was highest in the 50-59 years group (30.1%, 104/345). Immune diseases occurred in 18.6% (33/177) of patients, 24.3% (43/177) of patients had allergic skin diseases, and 5.6% (10/177) of the patients' immediate family members had chronic vulvar pruritus or vulvar hypopigmentation. (2) Clinical features: the most common symptom was vulvar pruritus (96.1%, 196/204) among 204 patients with recorded symptoms. The most common sign was hypopigmentation of the vulva (96.3%, 206/214). The most common involved sites were labia minora (70.3%, 142/202), labia majora (67.8%, 137/202), and labial sulcus (59.4%, 120/202). The cumulative number of sites involved in 62 vulvar atrophy patients (2.7±1.1) was significantly higher than that in 152 non-atrophy patients (2.2±1.0; t=3.48, P=0.001). The course of vulvar atrophy was (9.3±8.5) years, which was significantly longer than that of non-atrophy patients [(6.6±5.6) years; t=2.04, P=0.046]. (3) Pathological features: among the 286 patients with electronic pathological sections, the most common pathological feature in the epidermis was epithelial nail process passivation (71.3%, 204/286). The common pathological features in the dermis were interstitial collagenization (84.6%, 242/286), and inflammatory cell infiltration (73.8%, 211/286). (4) Treatment: 177 patients received standardized treatment after diagnosis and were followed up regularly in our hospital. In the initial treatment stage, 26.0% (46/177) of the patients were treated with 0.05% clobetasol propionate cream, and 74.0% (131/177) of the patients were treated with 0.1% mometasone furoate ointment. The complete remission rates of the two methods were respectively 80.4% (37/46) and 74.0% (97/131), and there was no statistically significant difference (χ²=0.76, P=0.385). During maintenance treatment, 27.1% (48/177) of the patients took the medication twice a week, 35.0% (62/177) took the medication once a week, and 37.9% (67/177) took the medication once every 10 days. During follow-up after 6 months of maintenance treatment, there were no patients with recurrence of pruritus or progression of vulvar signs. Conclusions: The majority of VLS patients have itching, hypopigmentation, involvement of labia minora and labia majora, progressive atrophy, and inflammatory infiltration of dermis. Local treatments of mometasone furoate and clobetasol propionate have good initial therapeutic effects. The frequency exploration of individualized maintenance treatment could minimize the occurrence of adverse reactions when ensuring the stability of the patients' condition.

Sensitivity of Pharmacokinetics to Differences in the Particle Size Distribution for Formulations of Locally Acting Mometasone Furoate Suspension-Based Nasal Sprays.

To assess bioequivalence of locally acting suspension-based nasal sprays, the U.S. FDA currently recommends a weight-of-evidence approach. In addition to in vitro and human pharmacokinetic (PK) studies, this includes a comparative clinical endpoint study to ensure equivalent bioavailability of the active pharmaceutical ingredient (API) at the site of action. The present study aimed to assess, within an in vitro/in vivo correlation paradigm, whether PK studies and dissolution kinetics are sensitive to differences in drug particle size for a locally acting suspension-based nasal spray product. Two investigational suspension-based nasal formulations of mometasone furoate (MF-I and MF-II; delivered dose: 180 µg) differed in API particle size and were compared in a single-center, double-blind, single-dose, randomized, two-way crossover PK study in 44 healthy subjects with oral charcoal block. Morphology-directed Raman spectroscopy yielded volume median diameters of 3.17 µm for MF-I and 5.50 µm for MF-II, and dissolution studies showed that MF-II had a slower dissolution profile than MF-I. The formulation with larger API particles (MF-II) showed a 45% smaller Cmax and 45% smaller AUC0-inf compared to those of MF-I. Systemic bioavailability of MF-I (2.20%) and MF-II (1.18%) correlated well with the dissolution kinetics, with the faster dissolving formulation yielding the higher bioavailability. This agreement between pharmacokinetics and dissolution kinetics cross-validated both methods and supported their use in assessing potential differences in slowly dissolving suspension-based nasal spray products.

The rising cost of rhinologic medications.

BACKGROUND: The high prescription drug cost in the United States may negatively affect patient prognosis and treatment compliance. OBJECTIVE: To fill the knowledge gap and inform clinicians regarding rhinology medications price changes by evaluating trends in price changes of highly used nasal sprays and allergy medications. METHODS: The 2014-2020 Medicaid National Average Drug Acquisition Cost database was queried for drug pricing information for the following classes of medications: intranasal corticosteroids, oral antihistamines, antileukotrienes, intranasal antihistamines, and intranasal anticholinergics. Individual medications were identified by Food and Drug Administration-assigned National Drug Codes. Per unit, drug prices were analyzed for average annual prices, average annual percentage price changes, and inflation-adjusted annual and composite percentage price changes. RESULTS: Beclometasone (Beconase AQ, 56.7%, QNASL, 77.5%), flunisolide (Nasalide, -14.6%), budesonide (Rhinocort Aqua, -1.2%), fluticasone (Flonase, -6.8%, Xhance, 11.7%), mometasone (Nasonex, 38.2%), ciclesonide (Omnaris, 73.8%), combination azelastine and fluticasone (Dymista, 27.3%), loratadine (Claritin, -20.5%), montelukast (Singulair, 14.5%), azelastine (Astepro, 21.9%), olopatadine (Patanase, 27.3%), and ipratropium bromide (Atrovent, 56.6%) had an overall change in inflation-adjusted per unit cost between 2014 and 2020 (% change). Of 14 drugs evaluated, 10 had an increase in inflation-adjusted prices, for an average increase of 42.06% ± 22.27%; 4 of 14 drugs had a decrease in inflation-adjusted prices, for an average decrease of 10.78% ± 7.36%. CONCLUSION: The rising cost of highly used medications contributes to increased patient acquisition costs and may pose barriers of drug adherence to particularly vulnerable populations.

Intranasal Olopatadine-Mometasone in the Treatment of Seasonal Allergic Rhinitis.

OBJECTIVE: To review the pharmacology, efficacy, and safety of intranasal olopatadine hydrochloride-mometasone furoate (OM) combination in the treatment of seasonal allergic rhinitis (SAR). DATA SOURCES: The PubMed database and ClinicalTrials.gov were searched using the following terms: mometasone + olopatadine, GSP301, mometasone furoate, and olopatadine hydrochloride. STUDY SELECTION AND DATA EXTRACTION: Articles published in English between January 1987 and August 2022 related to pharmacology, safety, and clinical trials were assessed. DATA SYNTHESIS: In 2 phase II clinical trials, twice-daily (BID) and once-daily (QDay) intranasal OM demonstrated significant improvements in reflective total nasal symptom score (rTNSS) (BID P < 0.001 and QDay P < 0.001) and instantaneous total nasal symptom score (iTNSS) (BID P < 0.001 and P < 0.0001; QDay P < 0.001 and P < 0.0001). In 2 phase III clinical trials, BID OM showed significant improvements in rTNSS vs. placebo (P < 0.001), olopatadine monotherapy (P = 0.03 and P = 0.003), and mometasone monotherapy (P = 0.02 and P = 0.059). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: OM is indicated for treatment of SAR symptoms. Caution with use must be considered for certain high-risk patients, existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. Due to its quick and sustained onset of action, OM may be an ideal agent for initial treatment of moderate-severe SAR for patients 12 years and older. CONCLUSION: OM significantly improves SAR symptoms and is a viable treatment option in short-term SAR.

Long-term safety of once-daily indacaterol acetate/glycopyrronium bromide/mometasone furoate high-dose, and indacaterol acetate/mometasone furoate high-dose, in Japanese patients with inadequately controlled asthma: Results from two open-label, 52-week studies.

INTRODUCTION: The 52-week long-term safety of once-daily indacaterol acetate/glycopyrronium bromide/mometasone furoate (IND/GLY/MF) high-dose (150/50/160 µg) and IND/MF high-dose (150/320 µg) was evaluated in two studies enrolling Japanese patients with inadequately controlled asthma. METHODS: Study 1 (IND/GLY/MF) and Study 2 (IND/MF) were 52-week, phase III, open-label, single-arm, multicenter studies conducted in Japanese adult patients with inadequately controlled asthma. The primary endpoint was incidence and severity of treatment-emergent adverse events (AEs) over 52-weeks. RESULTS: In Study 1, 94 patients received IND/GLY/MF high-dose and 84 (89.4%) patients completed the 52-week study treatment; in Study 2, 51 patients received IND/MF high-dose and 48 (94.1%) patients completed the 52-week study treatment. In Study 1, 68.1% and 6.4% of 94 patients reported ≥1 AE and ≥1 serious AE (SAE) respectively. In Study 2, 78.4% of 51 patients reported ≥1 AE; no patients reported SAEs. The most commonly reported AEs were asthma (exacerbation; 30.9% and 54.9%) and nasopharyngitis (18.1% and 29.4%) in Study 1 and Study 2, respectively. Severe AEs including asthma (exacerbation) were reported in 13.8% and 13.7% of patients in Study 1 and Study 2, respectively. In Study 1, 10 patients (10.6%) reported treatment-related AEs, of which dysphonia (9 patients [9.6%]) was the most commonly reported; no treatment-related AEs were reported in Study 2. In Study 1, one death (not study drug-related) was reported after study discontinuation (92 days after last dose of study medication). CONCLUSIONS: Once-daily IND/GLY/MF and IND/MF high-dose were well-tolerated in Japanese patients with inadequately controlled asthma. No unexpected safety findings were observed.Supplemental data for this article is available online at.

Does Clearance of Vulvar Lichen Sclerosus after a Corticosteroid Treatment Correspond to a Decrease in Disease-Related Burden? Results from a Cohort Study Using Pictorial Representation of Illness and Self-Measure and the Dermatology Life Quality Index.

BACKGROUND AND OBJECTIVES: Complete clearance of vulvar lichen sclerosus (VLS) occurs in a minority of treated patients. Disease persistence may impact patient well-being. The main objective of this study was to assess if achieving a complete clearance with a corticosteroid treatment leads to a benefit in terms of patient suffering and quality-of-life (QoL) impairment. METHODS: We performed an observational study on a cohort of VLS women, who applied mometasone furoate 0.1% ointment for 12 weeks. At treatment completion (T1), we compared the patients who achieved clearance in symptoms (Global Subjective Score [GSS] = 0) or in objective features (Global Objective Score [GOS] = 0) or in both with those who achieved a lower degree of improvement, on the basis of Pictorial Representation of Illness and Self-Measure (PRISM) and Dermatology Life Quality Index (DLQI) scores. RESULTS: In the whole sample (n = 101), GSS, GOS, PRISM, and DLQI scores significantly improved after treatment from baseline; 34 patients (35.8%) achieved GSS = 0, 26 (25.7%) achieved GOS = 0, and 11 (11.5%) clearance of GSS and GOS. PRISM scores at T1 were significantly higher in patients who achieved clearance of symptoms when compared with those who did not, including patients achieving 50-99% GSS improvement from baseline. DLQI scores were lower in patients who achieved clearance of symptoms, signs, or both when compared with the others. CONCLUSIONS: VLS clearance corresponded to a significant improvement in the QoL of VLS patients, also in comparison with those who achieved a substantial but incomplete decrease of symptom and sign scores, and should become an ideal therapeutic goal.

Phase 3b randomized controlled trial of fevipiprant in patients with nasal polyposis with asthma (THUNDER).

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with asthma, particularly of late onset. Current treatment options for CRSwNP have limitations, and there is an unmet need for other safe and effective therapies. OBJECTIVE: The aim of the THUNDER study was to determine the efficacy and safety of the prostaglandin D2 receptor 2 (DP2) antagonist fevipiprant in patients with CRSwNP and concomitant asthma, measured by improvement in nasal polyp score (primary end point), nasal congestion score, Sinonasal Outcome Test 22 score, and University of Pennsylvania Smell Identification Test score. METHODS: THUNDER was a phase 3b, randomized, multicenter, double-blind, placebo-controlled, parallel-group, 16-week study of fevipiprant 150 mg or 450 mg once daily versus placebo. All patients received intranasal mometasone furoate 200 µg daily. RESULTS: Ninety-eight patients were randomly assigned to fevipiprant 150 mg (n = 32), fevipiprant 450 mg (n = 34), or placebo (n = 32). Mean (SE) change from baseline in nasal polyp score at week 16 was 0.20 (0.224) for fevipiprant 150 mg, -0.10 (0.216) for fevipiprant 450 mg, and 0.14 (0.233) for placebo. Mean treatment difference was 0.05 (95% confidence interval, -0.59, 0.70; adjusted P = .979) for fevipiprant 150 mg versus placebo and -0.25 (95% confidence interval, -0.88, 0.39; adjusted P = .656) for fevipiprant 450 mg versus placebo. There was no meaningful difference in the secondary end points for fevipiprant versus placebo. CONCLUSIONS: THUNDER provided no evidence of a role for fevipiprant in the treatment of patients with CRSwNP and asthma; future studies may establish a role for other DP2 antagonists, specifically in patients with aspirin-exacerbated respiratory disease.

Multi-Gram Scale Synthesis and Characterization of Mometasone Furoate EP Impurity C.

Mometasone furoate is a synthetic corticosteroid used in the treatment of skin inflammatory conditions, hay fever and asthma. The industrial manufacturing routes to mometasone furoate are generally accompanied by the formation of numerous process impurities that need to be detected and quantified, as requested by regulatory authorities. The ready availability of such impurities in the required quantity and purity is therefore essential for toxicological studies, analytical method development and process validation. Herein, we report the multi-gram scale preparation of 21'-chloro-(16'α-methyl-3',11',20'-trioxo-pregna-1',4'-dien-17'-yl)-furan-2-carboxylate (mometasone furoate EP impurity C), one of the known impurities of mometasone furoate. This study also includes the systematic investigation of the final acylation step, as well as the characterization of the difuroate enol ether intermediate and its conversion to the target impurity C.

Meta-analysis and cost-effectiveness analysis of intranasal corticosteroid treatment in allergic rhinitis with ocular symptoms.

BACKGROUND: Intranasal corticosteroid (INCS) has a beneficial effect on ocular symptoms in allergic rhinitis (AR). To our knowledge, the cost-effectiveness of available INCS for AR with ocular symptoms is yet to be demonstrated. OBJECTIVE: To evaluate the cost-effectiveness of INCSs including Budesonide (BANS), Mometasone furoate (MFNS), Triamcinolone (TANS), and Fluticasone furoate (FFNS) on ocular symptoms associated with AR in the Thai context. METHODS: The percentage of effectiveness in improving total ocular symptoms score (TOSS) was derived from the result of a meta-analysis that estimated the SMD of each INCS treatment compared to placebo as clinical input parameters. A cost-effectiveness analysis based on a decision-tree model to assess one-year costs and outcomes from a Thai societal perspective. The outcomes were to compare incremental cost-effectiveness ratio (ICER). Probabilistic sensitivity analyses (PSA) were also conducted to capture parameter uncertainties. RESULTS: 13 eligible RCTs with a total of 3,722 patients with SAR were included in the analysis. The percentage of effectiveness of FFNS, MFNS, TANS, and BANS was 59.89%, 45.60%, 24.89%, and 16.00%, respectively. The ICER of FFNS, MFNS, and TANS is THB-6,539.92, 4,593.83, and 1,401.24 compared to BANS. CECA result showed the probability of using FFNS is considered cost-effective in 87.50% of cases from zero value followed by MFNS (0.80%), TANS (5.40%), and BANS (6.30%). With a threshold greater than THB20,000, FFNS is considered a cost-effective strategy. CONCLUSIONS: FFNS is a cost-effective option compared to alternative INCSs in Thailand for treating AR with ocular symptoms.

[Control of hormonal rhinitis symptoms in patients with hypothyrosis: pathogenetic and clinical aspects]. / Kontrol' simptomov khronicheskogo rinita u patsientov s gipotireozom: patogeneticheskie i klinicheskie aspekty.

BACKGROUND: One of the poorly studied sections of the pathology of ENT organs is chronic rhinitis in patients with hypothyroidism, the pathogenesis of which has not been fully understood, the diagnosis causes significant difficulties, and there are no recommendations for treatment. Despite receiving replacement therapy with levothyroxine, the symptoms of rhinitis persist. OBJECTIVE: To study the effectiveness of the use of intranasal glucocorticosteroids in patients with chronic rhinitis and hypothyroidism. MATERIAL AND METHODS: Patients with chronic rhinitis and hypothyroidism used mometasone nasal spray 100 mcg 1 time per day for a course of treatment of 2 months (n=60). To assess the symptoms of rhinitis, a visual analog scale (0-10 points), endoscopic examination of ENT organs, anterior active rhinomanometry were used. Evaluation of mucociliary transport was used a saccharin test. The concentration of transforming growth factor (TGF-ß1) in nasal secretion and blood serum was studied by ELISA (Enzyme-Linked Immunosorbent Assay), the number of metabolites of NO - nitrites+nitrates (NOx) was recorded by colorimetric method. RESULTS: The use of mometasone nasal spray in patients with hypothyroidism helped to reduce complaints on a visual-analog scale (difficulty in nasal breathing, rhinorrhea) and improve nasal breathing according to anterior active rhinomanometry. The concentrations of TGF-ß1 and NOx in nasal secretions before mometasone treatment were higher than after treatment, which probably indicates the contribution of these substances to the formation of edematous hypertrophic changes from the nose in patients with hypothyroidism.

Mometasone or Tiotropium in Mild Asthma with a Low Sputum Eosinophil Level.

BACKGROUND: In many patients with mild, persistent asthma, the percentage of eosinophils in sputum is less than 2% (low eosinophil level). The appropriate treatment for these patients is unknown. METHODS: In this 42-week, double-blind, crossover trial, we assigned 295 patients who were at least 12 years of age and who had mild, persistent asthma to receive mometasone (an inhaled glucocorticoid), tiotropium (a long-acting muscarinic antagonist), or placebo. The patients were categorized according to the sputum eosinophil level (<2% or ≥2%). The primary outcome was the response to mometasone as compared with placebo and to tiotropium as compared with placebo among patients with a low sputum eosinophil level who had a prespecified differential response to one of the trial agents. The response was determined according to a hierarchical composite outcome that incorporated treatment failure, asthma control days, and the forced expiratory volume in 1 second; a two-sided P value of less than 0.025 denoted statistical significance. A secondary outcome was a comparison of results in patients with a high sputum eosinophil level and those with a low level. RESULTS: A total of 73% of the patients had a low eosinophil level; of these patients, 59% had a differential response to a trial agent. However, there was no significant difference in the response to mometasone or tiotropium, as compared with placebo. Among the patients with a low eosinophil level who had a differential treatment response, 57% (95% confidence interval [CI], 48 to 66) had a better response to mometasone, and 43% (95% CI, 34 to 52) had a better response to placebo (P = 0.14). In contrast 60% (95% CI, 51 to 68) had a better response to tiotropium, whereas 40% (95% CI, 32 to 49) had a better response to placebo (P = 0.029). Among patients with a high eosinophil level, the response to mometasone was significantly better than the response to placebo (74% vs. 26%) but the response to tiotropium was not (57% vs. 43%). CONCLUSIONS: The majority of patients with mild, persistent asthma had a low sputum eosinophil level and had no significant difference in their response to either mometasone or tiotropium as compared with placebo. These data provide equipoise for a clinically directive trial to compare an inhaled glucocorticoid with other treatments in patients with a low eosinophil level. (Funded by the National Heart, Lung, and Blood Institute; SIENA ClinicalTrials.gov number, NCT02066298.).

Fitting Pharmacodynamic Data to the Emax Model to Assess the Inherent Potency of Topical Corticosteroids.

The widespread use of topical corticosteroids (TCs) in dermatotherapy requires a consideration of their potency and benefit/risk ratios. Although there are a variety of topical corticosteroid products (TCPs) available on the market and their potencies are ranked using different classification systems, to our knowledge, no classification system to rank the inherent potencies of TC active pharmaceutical ingredients (APIs) currently exists. Most of the published classification systems for TCPs are based on randomized clinical comparative studies and/or vasoconstrictor assay (VCA) data. The objective was to apply the US FDA's VCA to classify the inherent potencies of several TCs using standardized doses to make appropriate comparisons of the relevant APIs in solutions of the same molar concentrations. Six TC APIs were assessed for their relative potencies using healthy human participants. The Emax model was used to fit skin blanching data following application of the respective TCs, and the parameters, Emax and ED50, were derived. Emax values were used as the metric to assess potency. Statistical analyses of the data revealed that the inherent potencies of fluticasone propionate, mometasone furoate, and hydrocortisone butyrate were similar. However, there was no significant difference between hydrocortisone butyrate and clobetasol propionate, while there was a significant difference between clobetasol propionate, fluticasone propionate, and mometasone furoate. Hence, the potency of hydrocortisone butyrate appears to overlap two potency classes. Furthermore, the potencies of betamethasone valerate and methylprednisolone aceponate were similar but lower than those of all of the other APIs. The application of the VCA to classify inherent potency provides a reliable method to establish a classification system for TCs. Inherent potency assessment of TCs provides information that will be useful when choosing an appropriate TC for the development of a TCP for a specific clinical indication.

Comparative clinical pharmacology of mometasone furoate, fluticasone propionate and fluticasone furoate.

AIMS: To investigate the pharmacokinetics and effects on the hypothalamic-pituitary-adrenal (HPA) axis of mometasone furoate (MF), fluticasone propionate (FP) and fluticasone furoate (FF). METHODS: Study 1: Fourteen healthy participants received inhaled and intravenous MF (inhaled dose via Twisthaler) and FP (inhaled dose via Diskus), both given at 400 µg, using a randomised, single-dose, four-way crossover design. Study 2: Twenty-seven participants with mild to moderate asthma, who discontinued their corticosteroid medication for 5 days to obtain a baseline 24 h serum cortisol, received inhaled MF Twisthaler and FP Diskus, both given at 400 µg twice daily (BID), using a randomised, 14-day repeat dose, two-way crossover design. Study 3: Forty-four healthy participants were randomised to a double-blind, placebo-controlled, five-period crossover study where the following treatments were administered via the inhaled route for 7 days: FP Diskus (250, 500, 1000 µg BID), FF Diskus (100, 200, 400, 800, 1600 µg once daily [QD]) or placebo Diskus. In each study, 24-h serial blood samples were collected and assayed to assess concentrations of MF, 6ß-hydroxy mometasone, mometasone, FP, FF and cortisol. Pharmacokinetic and serum cortisol parameters were estimated as geometric means and 95% confidence intervals (CI). RESULTS: Study 1: For intravenous MF and FP, respectively: absolute bioavailability was 11.4% (95% CI: 7.5, 17.6) and 7.8% (6.3, 9.6); plasma clearance was 47 L/h (41, 52) and 60 L/h (52, 69); half-life was 7.4 h (6.9, 8.0) and 7.2 h (6.5, 8.0); and volume of distribution was 499 L (439, 567) and 623 L (557, 698). Inhalation of single dose MF or FP did not significantly affect serum cortisol (<10% reduction from baseline), whereas intravenous administration of MF or FP each changed serum cortisol by approximately -50% from baseline. Study 2: For MF and FP, respectively: area under the curve up to the last measurable concentration on Day 1 was 421 pg h/mL (270, 659) and 248 pg h/mL (154, 400), and on Day 14 was 1092 pg h/mL (939, 1269) and 591 pg h/mL (501, 696); absolute bioavailability was 12.8% (11.2, 14.2) and 8.9% (7.7, 10.2). On Day 14, 24-h serum cortisol change from baseline was -35% (-44%, -26%) and -18% (-28%, -5%) for MF and FP, respectively; the reduction was significantly greater for MF than FP (ratio for geometric adjusted mean serum cortisol concentration: 1.28 [1.04, 1.56]). Low plasma concentrations of 6ß-hydroxy mometasone were detected after intravenous dosing (Study 1) and after multiple inhaled dosing (Study 2); mometasone was not detected in any samples. Study 3: Inhaled FP and FF had similar systemic bioavailability estimates (12.0% [11.0, 13.2] and 15.0% [12.0, 17.3], respectively), but a differential effect on the HPA axis which was in agreement with the known 1.7-fold higher glucocorticoid receptor-binding affinity of FF versus FP. However, for FP 250 µg BID and FF 100, 200 and 400 µg QD, reduction in serum cortisol was not significantly different from placebo. For higher doses, FP 500 and 1000 µg BID, and FF 800 and 1600 µg QD, changes in serum cortisol concentration relative to placebo were -30%, -70%, -41% and -90%, respectively. Repeat inhaled dosing of FP 1000 µg/day (within the therapeutic dose range) resulted in comparable cortisol suppression to MF in the therapeutic range (30% reduction); whereas for FF this occurred at more than 3-fold above the therapeutic dose range (644 µg/day). CONCLUSIONS: Single inhaled and intravenous doses of MF and FP (400 µg) resulted in similar bioavailability and reductions in serum cortisol. Repeat dosing of inhaled MF and FP in the therapeutic range (800 µg/day) resulted in greater systemic exposure for MF, and a 35% reduction in serum cortisol that was 2-fold greater than for FP. The higher glucocorticoid receptor-binding affinity and bioavailability, lower clearance and the presence of active metabolites may contribute to the greater systemic exposure and effect on cortisol for MF. Repeat dosing of inhaled FP and FF resulted in similar systemic bioavailability but differed in terms of the dose required for comparable cortisol suppression to MF in the therapeutic range. Unlike FP and FF, MF has active metabolites that may contribute to its systemic effects, while device/formulation performance differences also exist between MF-containing products.