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JAMA Dermatology Mar 2021Systemic and inhaled corticosteroids negatively affect bone remodeling and cause osteoporosis and bone fracture when given continuously or in high doses. However, risk...
IMPORTANCE
Systemic and inhaled corticosteroids negatively affect bone remodeling and cause osteoporosis and bone fracture when given continuously or in high doses. However, risk of osteoporosis and major osteoporotic fracture (MOF) after application of topical corticosteroids (TCSs) is largely unexplored.
OBJECTIVE
To examine the association between cumulative exposure to potent and very potent TCSs and risk of osteoporosis and MOF.
DESIGN, SETTING, AND PARTICIPANTS
This nationwide retrospective cohort study included 723 251 Danish adults treated with potent or very potent TCSs from January 1, 2003, to December 31, 2017. Data were obtained from Danish nationwide registries. Filled prescription data were converted in equipotent doses to mometasone furoate (1 mg/g). Data were analyzed from June 1 to August 31, 2019.
EXPOSURES
Patients were considered exposed when they had filled prescriptions of cumulative amounts corresponding to the equivalent of at least 500 g of mometasone, using filled prescriptions of 200 to 499 g as the reference group.
MAIN OUTCOMES AND MEASURES
The co-primary outcomes were a diagnosis of osteoporosis or MOF. Hazard ratios (HRs) adjusted for age, sex, socioeconomic status, medication use, and comorbidity were calculated with 95% CIs using Cox proportional hazards regression models.
RESULTS
A total of 723 251 adults treated with the equivalent of at least 200 g of mometasone were included in the analysis (52.8% women; mean [SD] age, 52.8 [19.2] years). Dose-response associations were found between increased use of potent or very potent TCSs and the risk of osteoporosis and MOF. For example, HRs of MOF were 1.01 (95% CI, 0.99-1.03) for exposure to 500 to 999 g, 1.05 (95% CI, 1.02-1.08) for exposure to 1000 to 1999 g, 1.10 (95% CI, 1.07-1.13) for exposure to 2000 to 9999 g, and 1.27 (95% CI, 1.19-1.35) for exposure to at least 10 000 g. A 3% relative risk increase of osteoporosis and MOF was observed per doubling of the cumulative TCS dose (HR, 1.03 [95% CI, 1.02-1.04] for both). The overall population-attributable risk was 4.3% (95% CI, 2.7%-5.8%) for osteoporosis and 2.7% (95% CI, 1.7%-3.8%) for MOF. The lowest exposure needed for 1 additional patient to be harmed (454 person-years) was observed for MOF with exposure of at least 10 000 g.
CONCLUSIONS AND RELEVANCE
These findings demonstrate that use of high cumulative amounts of potent or very potent TCSs was associated with an increased risk of osteoporosis and MOF.
Topics: Administration, Topical; Adult; Aged; Cohort Studies; Denmark; Dose-Response Relationship, Drug; Female; Glucocorticoids; Humans; Male; Middle Aged; Mometasone Furoate; Osteoporosis; Osteoporotic Fractures; Registries; Retrospective Studies; Risk Assessment
PubMed: 33471030
DOI: 10.1001/jamadermatol.2020.4968 -
Pulmonary Therapy Sep 2023GINA guidelines recommend increasing the dose of inhaled corticosteroids (ICS) as a step-up option for patients with inadequately controlled asthma at GINA step 4...
INTRODUCTION
GINA guidelines recommend increasing the dose of inhaled corticosteroids (ICS) as a step-up option for patients with inadequately controlled asthma at GINA step 4 [inadequately controlled asthma on medium-dose ICS/long-acting beta-2 agonist (LABA)]. The aim of this study was to compare the efficacy and safety of long-acting muscarinic antagonists (LAMA) add-on to medium-dose ICS/LABA in patients at GINA 2022 step 4.
METHODS
This post hoc analysis of the IRIDIUM study evaluated the change from baseline in trough forced expiratory volume (FEV ) in patients receiving medium-dose MF/IND/GLY versus high-dose MF/IND and high-dose FLU/SAL at Week 26. Other outcomes included improvement in lung functions [peak expiratory flow (PEF), forced vital capacity (FVC), forced expiratory flow between 25% and 75% of the FVC (FEF))], asthma control [Asthma Control Questionnaire (ACQ-7)], responder analysis (≥ 0.5 unit improvement in ACQ-7), and reduction in asthma exacerbations at Weeks 26 and 52.
RESULTS
A total of 1930 patients were included in this analysis. Medium-dose MF/IND/GLY improved trough FEV versus high-dose MF/IND (Δ 41 mL; 95% CI - 7-90) and high-dose FLU/SAL (Δ 88 mL; 95% CI 39-137) at Week 26 which were sustained until Week 52. Exacerbation rates were 16% lower with medium-dose MF/IND/GLY versus high-dose MF/IND for all (mild, moderate, and severe) exacerbations and 21-30% lower versus high-dose FLU/SAL for all (mild, moderate, and severe), moderate or severe, and severe exacerbations over 52 weeks. Further improvements in other lung functions were observed with medium-dose MF/IND/GLY. No new safety signals were identified.
CONCLUSION
Medium-dose MF/IND/GLY improved lung function and reduced asthma exacerbations compared to high-dose ICS/LABA and may be an undervalued option in patients at GINA 2022 step 4.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02571777.
PubMed: 37526856
DOI: 10.1007/s41030-023-00234-y -
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 -
Revista Brasileira de Enfermagem 2020to analyze the effectiveness of skin protectors and Calendula officinalis for prevention and treatment of radiodermatitis. (Review)
Review
OBJECTIVE
to analyze the effectiveness of skin protectors and Calendula officinalis for prevention and treatment of radiodermatitis.
METHOD
an integrative review conducted at CINAHL, Cochrane Library, Embase, MEDLINE/PubMed, IBECS, LILACS, and Web of Science. The final sample consisted of five studies, four clinical studies and one preclinical. Critical appreciation and narrative synthesis of the findings were carried out.
RESULTS
the Cavilon™ skin protector was more effective than Sorbolene (cream with 10% glycerin) and less effective than Mometasone Furoate cream. Calendula officinalis was more effective than Trolamine and essential fatty acids and less effective than Ching Wan Hung® for prevention and treatment of radiodermatitis.
CONCLUSION
data confirm the potential of Calendula officinalis for prevention and treatment of radiodermatitis and point to promising results regarding skin protector use; however, there is a need for further testing as to the effectiveness of such products.
Topics: Calendula; Humans; Phytotherapy; Plant Extracts; Radiodermatitis
PubMed: 33084806
DOI: 10.1590/0034-7167-2019-0815 -
American Journal of Otolaryngology 2008Treatment guidelines for acute rhinosinusitis (RS) recommend the use of intranasal corticosteroids (INSs) as monotherapy or adjunctive therapy. However, the adverse... (Review)
Review
Treatment guidelines for acute rhinosinusitis (RS) recommend the use of intranasal corticosteroids (INSs) as monotherapy or adjunctive therapy. However, the adverse event (AE) profiles of oral glucocorticoids, which result largely from the systemic absorption of those agents, have engendered concerns about the safety of INSs. These concerns persist for INSs despite significant or marked clinical differences between them and systemic corticosteroids in systemic absorption and among the INSs in bioavailability, mechanism of action, and lipophilicity, which may contribute to differences in AEs. For example, the systemic bioavailability of the INSs as a percentage of the administered drug is less than 0.1% for mometasone furoate, less than 1% for fluticasone propionate, 46% for triamcinolone acetonide, and 44% for beclomethasone dipropionate. A review of the safety profiles of INSs, as reported in clinical trials in acute and chronic RS and allergic rhinitis, shows primarily local AEs (eg, epistaxis and headache) that are generally classified as mild to moderate, with occurrence rates that are similar to those with placebo. Studies of the safety of mometasone furoate, fluticasone propionate, budesonide, and triamcinolone acetonide did not identify any evidence of systemic AEs, such as growth retardation in children due to suppression of the hypothalamic-pituitary-adrenal axis, bone mineral density loss, or cataracts, which suggests that INSs can be safely administered in patients with acute RS without concern for systemic AEs.
Topics: Acute Disease; Administration, Intranasal; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Androstadienes; Budesonide; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Female; Fluticasone; Humans; Male; Middle Aged; Mometasone Furoate; Pregnadienediols; Prognosis; Randomized Controlled Trials as Topic; Rhinitis; Risk Assessment; Sinusitis; Treatment Outcome; Young Adult
PubMed: 19144302
DOI: 10.1016/j.amjoto.2007.11.004 -
Clinical and Translational Allergy Jul 2021The pathogenesis of contact dermatitis, a common inflammatory skin disease with limited treatment options, is held to be driven by inflammasome activation induced by...
BACKGROUND
The pathogenesis of contact dermatitis, a common inflammatory skin disease with limited treatment options, is held to be driven by inflammasome activation induced by allergens and irritants. We here aim to identify inflammasome-targeting treatment strategies for irritant contact dermatitis.
METHODS
A high content screen with 41,184 small molecules was performed using fluorescent Apoptosis associated speck-like protein containing a CARD (ASC) speck formation as a readout for inflammasome activation. Hit compounds were validated for inhibition of interleukin (IL)-1β secretion. Of these, the approved thiuramdisulfide derivative disulfiram was selected and tested in a patch test model of irritant contact dermatitis in 25 healthy volunteers. Topical application of disulfiram, mometasone or vehicle was followed by application of sodiumdodecylsulfate (SDS) for 24 h each. Eczema induction was quantified by mexameter and laser speckle imaging. Corneocyte sampling of lesional skin was performed to assess inflammasome-mediated cytokines IL-1β and IL-18.
RESULTS
Disulfiram induced a dose-dependent inhibition of ASC speck formation and IL-1β release in cellular assays in vitro. In vivo, treatment with disulfiram, but not with vehicle and less mometasone, inhibited SDS-induced eczema. This was demonstrated by significantly lower erythema and total perfusion values assessed by mexameter and laser speckle imaging for disulfiram compared to vehicle ( < 0.001) and/or mometasone ( < 0.001). Also, corneocyte IL-18 levels were significantly reduced after application of disulfiram compared to vehicle ( < 0.001).
CONCLUSION
We show that disulfiram is a dose-dependent inhibitor of inflammasome pathway activation in vitro and inhibitor of SDS-induced eczema in vivo. Topical application of disulfiram represents a potential treatment option for irritant contact dermatitis.
PubMed: 34322217
DOI: 10.1002/clt2.12045 -
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 -
The Cochrane Database of Systematic... Apr 2016This review is one of six looking at the primary medical management options for patients with chronic rhinosinusitis.Chronic rhinosinusitis is common and is... (Review)
Review
BACKGROUND
This review is one of six looking at the primary medical management options for patients with chronic rhinosinusitis.Chronic rhinosinusitis is common and is characterised by inflammation of the lining of the nose and paranasal sinuses leading to nasal blockage, nasal discharge, facial pressure/pain and loss of sense of smell. The condition can occur with or without nasal polyps. Topical (intranasal) corticosteroids are used with the aim of reducing inflammation in the sinonasal mucosa in order to improve patient symptoms.
OBJECTIVES
To assess the effects of different types of intranasal steroids in people with chronic rhinosinusitis.
SEARCH METHODS
The Cochrane ENT Information Specialist searched the ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 7); MEDLINE; EMBASE; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 11 August 2015.
SELECTION CRITERIA
Randomised controlled trials (RCTs) with a follow-up period of at least three months comparing first-generation intranasal corticosteroids (e.g. beclomethasone dipropionate, triamcinolone acetonide, flunisolide, budesonide) with second-generation intranasal corticosteroids (e.g. ciclesonide, fluticasone furoate, fluticasone propionate, mometasone furoate, betamethasone sodium phosphate), or sprays versus drops, or low-dose versus high-dose intranasal corticosteroids.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane. Our primary outcomes were disease-specific health-related quality of life (HRQL), patient-reported disease severity and the commonest adverse event - epistaxis (nosebleed). Secondary outcomes included general HRQL, endoscopic nasal polyp score, computerised tomography (CT) scan score and the adverse event of local irritation. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.
MAIN RESULTS
We included nine RCTs (911 participants), including four different comparisons. None of the studies evaluated our first primary outcome measure, disease-specific HRQL. Fluticasone propionate versus beclomethasone dipropionate We identified two small studies (56 participants with polyps) that evaluated disease severity and looked at the primary adverse effect: epistaxis , but no other outcomes. We cannot report any numerical data but the study authors reported no difference between the two steroids. The evidence was of very low quality. Fluticasone propionate versus mometasone furoate We identified only one study (100 participants with polyps) that evaluated disease severity (nasal symptoms scores), which reported no difference (no numerical data available). The evidence was of very low quality. High-dose versus low-dose steroidsWe included five studies (663 participants with nasal polyps), three using mometasone furoate (400 µg versus 200 µg in adults and older children, 200 µg versus 100 µg in younger children) and two using fluticasone propionate drops (800 µg versus 400 µg). We found low quality evidence relating to disease severity and nasal polyps size, with results from the high-dose and low-dose groups being similar. Although all studies reported more improvement in polyp score in the high-dose group, the significance of this is unclear due to the small size of the improvements.The primary adverse effect, epistaxis , was more common when higher doses were used (risk ratio (RR) 2.06, 95% confidence interval (CI) 1.20 to 3.54, 637 participants, moderate quality evidence). Most of the studies that contributed data to this outcome used a broad definition of epistaxis, which ranged from frank bleeding to bloody nasal discharge to flecks of blood in the mucus. Aqueous nasal spray versus aerosol spray We identified only one poorly reported study (unclear number of participants for comparison of interest, 91 between three treatment arms), in which there were significant baseline differences between the participants in the two groups. We were unable to draw meaningful conclusions from the data.
AUTHORS' CONCLUSIONS
We found insufficient evidence to suggest that one type of intranasal steroid is more effective than another in patients with chronic rhinosinusitis, nor that the effectiveness of a spray differs from an aerosol. We identified no studies that compared drops with spray.It is unclear if higher doses result in better symptom improvements (low quality evidence), but there was moderate quality evidence of an increased risk of epistaxis as an adverse effect of treatment when higher doses were used. This included all levels of severity of epistaxis and it is likely that the proportion of events that required patients to discontinue usage is low due to the low numbers of withdrawals attributed to it. If epistaxis is limited to streaks of blood in the mucus it may be tolerated by the patient and it may be safe to continue treatment. However, it may be a factor that affects compliance.There is insufficient evidence to suggest that the different types of corticosteroid molecule or spray versus aerosol have different effects. Lower doses have similar effectiveness but fewer side effects.Clearly more research in this area is needed, with specific attention given to trial design, disease-specific health-related quality of life outcomes and evaluation of longer-term outcomes and adverse effects.
Topics: Administration, Intranasal; Adult; Beclomethasone; Child; Chronic Disease; Fluticasone; Humans; Mometasone Furoate; Nasal Polyps; Nasal Sprays; Randomized Controlled Trials as Topic; Rhinitis; Sinusitis; Steroids
PubMed: 27115215
DOI: 10.1002/14651858.CD011993.pub2 -
MedGenMed : Medscape General Medicine Jan 2006The purpose of this review is to describe the similarities and differences among the 4 aqueous once-daily intranasal corticosteroids (INS) for the treatment of allergic... (Comparative Study)
Comparative Study Review
OBJECTIVE
The purpose of this review is to describe the similarities and differences among the 4 aqueous once-daily intranasal corticosteroids (INS) for the treatment of allergic rhinitis (AR). INS are the recommended first-line therapy for all patients with AR that is greater than mild intermittent in severity. DATA SOURCE/STUDY SELECTION: Data were obtained from MEDLINE searches of all English-language articles published from January 1966 to January 2005 with the following search terms: allergic rhinitis and intranasal corticosteroid, nasal steroid, budesonide aqueous nasal spray, fluticasone propionate nasal spray, mometasone furoate nasal spray, or triamcinolone acetonide nasal spray. Also selected for review were data from published abstracts from recent scientific meetings.
DATA EXTRACTION
Data comparing efficacy, safety, patient preferences, and cost-effectiveness of any of the 4 available aqueous once-daily INS were extracted from the studies and are summarized.
CONCLUSION
All 4 aqueous once-daily INS available in the United States for the treatment of AR are similar with regard to efficacy and safety at the recommended starting dose. However, differences in patient preference, cost, and safety of use during pregnancy may contribute to primary care physicians' selection of an INS therapy for their patients.
Topics: Administration, Intranasal; Adrenal Cortex Hormones; Drug Administration Schedule; Humans; Patient Satisfaction; Rhinitis, Allergic, Perennial
PubMed: 16915153
DOI: No ID Found -
Pharmaceutics Sep 2021The potencies of topical corticosteroid products have mainly been classified using clinical data but in some instances, the US Food and Drug Administration's (FDA's)...
The potencies of topical corticosteroid products have mainly been classified using clinical data but in some instances, the US Food and Drug Administration's (FDA's) vasoconstrictor assay (VCA) to assess the skin blanching response has also been used. However, the reported skin blanching response data were often based on a single visual reading and lack information on the dose (amount/quantity) or dose duration. Although several lists classifying potencies of various topical corticosteroid products have been published, the inherent potencies of topical corticosteroid raw materials used as active pharmaceutical ingredients (APIs) have not been investigated. The objective was to rank the inherent potencies of topical corticosteroid APIs and to standardize dosing such that the relevant compounds could be compared on a normalized molar basis. The potencies of clobetasol propionate, halcinonide, mometasone furoate, and fluocinolone acetonide were compared using the resulting data following the fitting of the relevant response data to the model where mometasone furoate > fluocinolone acetonide = clobetasol propionate > halcinonide. This ranking lists the respective inherent potencies of the APIs, which will facilitate the choice of a suitable candidate for incorporation into an appropriate topical corticosteroid product for a specific clinical indication.
PubMed: 34575532
DOI: 10.3390/pharmaceutics13091456