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Clinical Drug Investigation Sep 2023Indacaterol acetate (IND), a long-acting β-agonist in combination with mometasone furoate (MF), an inhaled corticosteroid (ICS), is being explored as a once-daily (od)... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Indacaterol acetate (IND), a long-acting β-agonist in combination with mometasone furoate (MF), an inhaled corticosteroid (ICS), is being explored as a once-daily (od) treatment for asthma in children. This study examined the efficacy, safety, and systemic exposure of IND 75 µg and IND 150 µg in children with persistent asthma.
METHODS
In this Phase IIb, multicenter, randomized, double-blind, parallel-group study, pediatric patients (aged ≥ 6 to < 12 years) with persistent asthma were randomized (1:1) to receive either IND 75 µg od or IND 150 µg od via Breezhaler in combination with ICS background therapy. The primary endpoint was change from baseline in pre-dose trough forced expiratory volume in one second (FEV) after two weeks of treatment.
RESULTS
In total, 80 patients received IND 75 µg (n = 39) or IND 150 µg (n = 41). The study met its primary endpoint; both doses demonstrated improvements in pre-dose trough FEV from baseline to Day 14 (mean change [Δ]: 212 mL, IND 75 µg; 171 mL, IND 150 µg). The secondary spirometry parameters (post-dose FEV after 1-h, post-dose forced vital capacity; morning and evening peak expiratory flow) also improved. Overall, 36.1% in IND 75 μg group and 25% patients in IND 150 μg group achieved a decrease from baseline in Pediatric Interviewer-administered Asthma Control Questionnaire score of ≥ 0.5 units. A dose-dependent increase in plasma IND concentration was noted between the two groups. Both IND doses demonstrated an acceptable safety profile.
CONCLUSIONS
Once-daily IND 75 μg and IND 150 μg via Breezhaler in combination with background ICS therapy provided substantial bronchodilation in children with asthma and were well tolerated. Taken together, these clinical and systemic exposure findings support IND 75 μg as the most appropriate dose for evaluation in Phase III trials in combination with MF in pediatric asthma.
TRIAL REGISTRATION
ClinicalTrials.gov (NCT02892019; 08-Sep-2016).
Topics: Humans; Child; Asthma; Double-Blind Method; Forced Expiratory Volume; Acetates
PubMed: 37682405
DOI: 10.1007/s40261-023-01300-8 -
Journal of Personalized Medicine Nov 2023The nasal microbiome represents the main environmental factor of the inflammatory process in chronic rhinosinusitis (CRS). Antibiotics and steroids constitute the... (Review)
Review
BACKGROUND
The nasal microbiome represents the main environmental factor of the inflammatory process in chronic rhinosinusitis (CRS). Antibiotics and steroids constitute the mainstay of CRS therapies. However, their impact on microbial communities needs to be better understood. This systematic review summarizes the evidence about antibiotics' and steroids' impact on the nasal microbiota in patients with CRS.
METHODS
The search strategy was conducted in accordance with the PRISMA guidelines for systematic reviews. The authors searched all papers in the three major medical databases (PubMed, Scopus, and Cochrane Library) using the PICO tool (population, intervention, comparison, and outcomes). The search was carried out using a combination of the key terms "Microbiota" or "Microbiome" and "Chronic Rhinosinusitis".
RESULTS
Overall, 402 papers were identified, and after duplicate removal (127 papers), excluding papers off-topic (154) and for other structural reasons (110), papers were assessed for eligibility; finally, only 11 papers were included and summarized in the present systematic review. Some authors used only steroids, other researchers used only antibiotics, and others used both antibiotics and steroids. With regard to the use of steroids as exclusive medical treatment, topical mometasone and budesonide were investigated. With regard to the use of antibiotics as exclusive medical treatments, clarithromycin, doxycycline, roxithromycin, and amoxicillin clavulanate were investigated. Regarding the use of both antibiotics and steroids, two associations were investigated: systemic prednisone combined with amoxicillin clavulanate and topical budesonide combined with azithromycin.
CONCLUSIONS
The impact that therapies can have on the nasal microbiome of CRS patients is very varied. Further studies are needed to understand the role of the nasal microbiome, prevent CRS, and improve therapeutic tools for personalized medicine tailored to the individual patient.
PubMed: 38003898
DOI: 10.3390/jpm13111583 -
Drug Delivery and Translational Research Nov 2023Mometasone furoate (MF) is a synthetic glucocorticoid used clinically to treat specific inflammatory disorders including superior and inferior respiratory tract. Due to...
Mometasone furoate (MF) is a synthetic glucocorticoid used clinically to treat specific inflammatory disorders including superior and inferior respiratory tract. Due to its poor bioavailability we further investigated whether nanoparticles (NPs) made of zein protein may constitute a safe and effective choice to incorporate MF. Thus, in this work, we loaded MF into zein NPs aiming to evaluate possible advantages that could result from oral delivery and extend the range of MF application such as inflammatory gut diseases. MF-loaded zein NPs presented an average size in the range of 100 and 135 nm, narrow size distribution (polydispersity index < 0.300), zeta potential of around + 10 mV and association efficiency of MF over 70%. Transmission electron microscopy imaging revealed that NPs had a round shape and presented a smooth surface. The zein NPs showed low MF release in a buffer that mimics the gastric condition (pH = 1.2) and slower and controlled MF release in the intestinal condition (pH = 6.8). The short and intermediate safety of zein NPs was confirmed assessing the incubation against Caco-2 and HT29-MTX intestinal cells up to 24 h. Permeability studies of MF across Caco-2/HT29-MTX co-culture monolayer evidenced that zein NPs modulated MF transport across cell monolayer resulting in a stronger and prolonged interaction with mucus, potentially extending the time of absorption and overall local and systemic bioavailability. Overall, zein NPs showed to be suitable to carry MF to the intestine and future studies can be developed to investigate the use of MF-loaded zein NPs to treat intestinal inflammatory diseases.
Topics: Humans; Mometasone Furoate; Zein; Caco-2 Cells; Nanoparticles; Drug Carriers
PubMed: 37208563
DOI: 10.1007/s13346-023-01367-y -
Journal of Pharmacy & Bioallied Sciences Apr 2024Dermoscopy particularly could be helpful in patients with steroid damaged face to assess and look for the damage caused by the steroid creams as also in cases where the...
BACKGROUND AND OBJECTIVES
Dermoscopy particularly could be helpful in patients with steroid damaged face to assess and look for the damage caused by the steroid creams as also in cases where the patient provides improper history.
MATERIALS AND METHODS
Patients attending to dermatology OPD with suspected/diagnosed TSDF between the ages of 18 and 60 years were enrolled and assessed on the basis of age, gender, residence, duration, potency, brand of application topical steroid creams, clinical and dermoscopic features.
RESULTS
Majority abusing the topical steroid creams were females (n-14) with mean age with SD of 34 ± 11 and were from rural areas (57.8%). Red raised lesions were the most common clinical presentation (n-15) with telangiectasias as the most common dermoscopic feature (n-26). Triple combination creams containing hydroquinone 2%, tretinoin 0.025%, and 0.1% mometasone were on the top of the list (n-20).
CONCLUSION
In this study, the importance of dermoscopy in assessing the features of topical steroid damaged face and preventing further damage is highlighted. Various factors causing topical steroid creams misuse and the easy availability of the creams is to be kept on check.
PubMed: 38882848
DOI: 10.4103/jpbs.jpbs_1191_23 -
Skin Health and Disease Dec 2023Atopic dermatitis (AD) is one of the most common inflammatory skin diseases. It is associated with significant itch and impaired quality of life. Systemic treatments are...
BACKGROUND
Atopic dermatitis (AD) is one of the most common inflammatory skin diseases. It is associated with significant itch and impaired quality of life. Systemic treatments are efficient but associated with side effects. Novel topical treatments with a favourable safety profile are needed. SNG100 is a novel composition of hydrocortisone 1% in a cream base comprising sulphated polysaccharide (SPS; extracted from in-house cultivated Porphyridium Cruentum unicellular algae), a well-known hydrating, moisturising and a skin barrier repairing agent.
OBJECTIVES
To assess the safety, usability and efficacy of SNG100 cream in patients aged ≥6 years with moderate AD.
METHODS
In this proof of concept phase I, double-blind, randomised trial, participants received one of three treatments for 14 days: SNG100 twice daily (BID), hydrocortisone 1% BID or mometasone furoate once daily (QD). The primary endpoint was the safety and tolerability of SNG100 cream compared to hydrocortisone 1% and mometasone furoate. The secondary endpoint was the subject's usability of SNG100. Exploratory efficacy endpoints included percent change from baseline in SCOring AD (SCORAD), Eczema Area and Severity Index, Patient-Oriented Eczema Measure, Dermatology Life Quality Index, pruritus Numerical Rating Score (NRS), peak pruritus-NRS and Investigator's Global Assessment. Subjects were also followed up without any treatment for additional 14 days.
RESULTS
Overall, 66 participants were screened, and 60 patients were randomised. SNG100 demonstrated a high safety profile, similar to marketed products hydrocortisone 1% and mometasone furoate 0.1%, with no unanticipated drug safety related events. SNG100 and mometasone furoate 0.1% cream achieved almost similar and statistically significant greater percentage reductions from baseline in SCORAD as compared to hydrocortisone 1% cream. SNG100 demonstrated significant improvement in NRS as compared to hydrocortisone 1% cream. Remarkably, SNG100 led to a lasting effect with only 29.4% of subjects returning to IGA3 during the follow-up period compared to 50% and 38.9% in the hydrocortisone 1% and in mometasone furoate treatment arms, respectively.
CONCLUSIONS
Topical SNG100 is an effective, safe, and well-tolerated innovative treatment for moderate AD. Trial registration number: NCT04615962 (Topical Cream SNG100 for Treatment in Moderate AD Subjects).
PubMed: 38047249
DOI: 10.1002/ski2.293 -
Asian Pacific Journal of Allergy and... Dec 2023Intranasal corticosteroid (INCS) has a beneficial effect on ocular symptoms in allergic rhinitis (AR). To our knowledge, the cost-effectiveness of available INCS for AR... (Meta-Analysis)
Meta-Analysis
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.
Topics: Humans; Rhinitis, Allergic, Seasonal; Cost-Effectiveness Analysis; Rhinitis, Allergic; Administration, Intranasal; Adrenal Cortex Hormones; Mometasone Furoate; Anti-Allergic Agents; Treatment Outcome
PubMed: 37874315
DOI: 10.12932/AP-070823-1669 -
Cureus Nov 2023Aims The cost-effective therapy of immunosuppressant drugs in dermatological conditions will not only lead to adherence to rational prescribing but will also increase...
Aims The cost-effective therapy of immunosuppressant drugs in dermatological conditions will not only lead to adherence to rational prescribing but will also increase patient compliance with fewer dropouts due to cost factor. Thus, this study was done to determine and compare the drug utilization pattern, prescribed daily dose/defined daily dose (PDD/DDD) defined by WHO, and the cost-effectiveness ratio of different immunosuppressants. Methods and material Prescriptions for patients with skin disorders prescribed with any one systematic or topical immunosuppressant were collected. The utilization of drugs in different skin disorders was expressed as frequency and percentage. PDD was compared with DDD as per the WHOCC-Anatomical Therapeutic Chemical (ATC)/DDD index. The pharmacoeconomic analysis was done using a cost-effectiveness ratio. Statistical analysis Descriptive statistics were used to calculate percentages, frequency, and 95% CI. The cost-effectiveness ratio in terms of SFDs (symptom-free days) was defined as the total cost of the initial antibiotic during the study period divided by the number of SFDs (cost/ SFD) and was expressed as mean±standard deviation, and the Kruskal-Wallis test was used to determine statistical significance of difference. Results Immunosuppressants were prescribed in 117 (19.12%) prescriptions out of a total of 612 prescriptions. Deflazacort was the most utilized systemic immunosuppressant prescribed in 27.18% of cases and was commonly prescribed for irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD) followed by prednisolone and betamethasone. Tacrolimus was the most utilized topical immunosuppressant prescribed in 15.90% of patients and was commonly used for ICD and vitiligo followed by clobetasol and mometasone. Betamethasone, prednisolone, clobetasol, and mometasone had better cost-effectiveness. PDD/DDD of all immunosuppressants was less than one except prednisolone, which had a PDD/DDD ratio of 3.52. Conclusions The cost-effectiveness of steroids has the advantage of providing better patients' adherence to pharmacotherapy, but over-prescribing could also lead to long-term adverse effects of steroids. Pharmacovigilance research should also incorporate pharmacoeconomic analysis to determine the relation between these two aspects.
PubMed: 37954626
DOI: 10.7759/cureus.48541 -
Iranian Journal of Otorhinolaryngology Mar 2024Adenoid hypertrophy is a common childhood disease; its standard treatment is adenoidectomy. The desire for medical management is increasing due to fewer complications...
INTRODUCTION
Adenoid hypertrophy is a common childhood disease; its standard treatment is adenoidectomy. The desire for medical management is increasing due to fewer complications and more convenience. The present study investigated the effect of adding oral montelukast to mometasone nasal spray in treating adenoid hypertrophy.
MATERIALS AND METHODS
This was a randomized, double-blind, placebo-controlled study conducted at a referral teaching hospital (Tehran, Iran) from September 2020 to September 2021. Children aged 2 to 14 years with clinical and radiological findings of adenoid hypertrophy were enrolled. Patients were randomly divided into two groups: mometasone nasal spray with oral montelukast (case group) or mometasone with placebo (control group). Then, the clinical scores were compared before and two months after the intervention.
RESULTS
Ninety-six patients completed the study [62.5% male (n=60)]. Of these, 51 were in the case and 45 in the control group. The clinical score in each group decreased significantly after the intervention (P<0.001), but the decrease in clinical score in the case group was not significantly different from the control (p=0.576).
CONCLUSION
The results showed that the combination therapy with mometasone and montelukast has the same efficacy as mometasone and placebo in treating adenoid hypertrophy. Adding montelukast to mometasone has no additional effect.
PubMed: 38476566
DOI: 10.22038/IJORL.2024.73906.3490 -
International Journal of Nanomedicine 2023We designed a 0.05% mometasone furoate (MF) nanocrystal dispersion and investigated whether the application of MF nanocrystals in nasal formulations enhanced local...
PURPOSE
We designed a 0.05% mometasone furoate (MF) nanocrystal dispersion and investigated whether the application of MF nanocrystals in nasal formulations enhanced local absorption compared to traditional nasal MF formulations (CA-MF).
METHODS
MF nanocrystal dispersions (MF-NPs) were prepared by bead milling MF microcrystal dispersions (MF-MPs) consisting of MF, 2-hydroxypropyl-β-cyclodextrin, methylcellulose, and purified water. Pluronic F-127 combined with methylcellulose, Pluronic F-68, or carbopol was used as a base for in situ gelation (thickener). MF concentrations were measured using high-performance liquid chromatography, and nasal absorption of MF was evaluated in 6 week-old male Institute of Cancer Research (ICR) mice.
RESULTS
The particle size range of MF prepared with the bead mill treatment was 80-200 nm, and the nanoparticles increased the local absorption of MF, which was higher than that of CA-MF and MF-MPs. In addition, unlike the results obtained in the small intestine and corneal tissue, the high absorption of nanocrystalline MF in the nasal mucosa was related to a pathway that was not derived from energy-dependent endocytosis. Moreover, the application of the in situ gelling system attenuated the local absorption of MF-NPs, owing to a decrease in drug diffusion in the dispersions.
CONCLUSION
We found that nanoparticulation of MF enhances local intranasal absorption, and nasal bioavailability is higher than that of CA-MF. In addition, we demonstrate that viscosity regulation is an important factor in the design of nasal formulations based on MF nanocrystals. These findings provide insights for the design of novel nanomedicines with enhanced nasal bioavailability.
Topics: Male; Animals; Mice; Mometasone Furoate; Nasal Absorption; Nasal Mucosa; Methylcellulose
PubMed: 37841023
DOI: 10.2147/IJN.S430952 -
The Journal of Dermatological Treatment Dec 2024Dupilumab is a novel treatment agent for moderate to severe atopic dermatitis (AD) with few adverse effects. Drug-induced psoriasiform lesions are rare. We report a...
Dupilumab is a novel treatment agent for moderate to severe atopic dermatitis (AD) with few adverse effects. Drug-induced psoriasiform lesions are rare. We report a 4-year-old boy with AD who developed pustular psoriasis during treatment with dupilumab. Pustular psoriasis appeared within 1 week of treatment and worsened in the second week. After stopping dupilumab administration, topical corticosteroids (desonide and mometasone furoate creams) and oral desloratadine without relief. Pustular psoriasis was confirmed by pathological examination, and thiamphenicol was administered. After 2 weeks of treatment, the lesions nearly resolved without recurrence in 1-year follow-up. Dupilumab-induced pustular psoriasis is rare in children.
Topics: Humans; Male; Psoriasis; Antibodies, Monoclonal, Humanized; Child, Preschool; Dermatitis, Atopic; Mometasone Furoate; Dermatologic Agents
PubMed: 38839072
DOI: 10.1080/09546634.2024.2333016