Ciclesonide: a novel inhaled corticosteroid

Inhaled corticosteroids (ICS) are a mainstay in the treatment of persistent asthma, a disease with increasing prevalence and cost implications worldwide. However, long-term use of currently available ICS is associated with local adverse effects that include hoarseness and oral candidiasis. In addition, systemic adverse effects including adrenal cortical suppression, osteoporosis, growth retardation, cataracts and glaucoma are also present. Ciclesonide is a novel ICS, which promises to provide airway anti-inflammatory efficacy that is comparable with that of the available ICS in addition to reducing the risk for local and systemic adverse events. Ciclesonide is an agent that is inactive until it reaches its target site, the lung, where it is converted to its active metabolite desisobutyryl-ciclesonide. In addition, other favourable pharmacokinetic and pharmacodynamic characteristics such as high protein binding, low oral bioavailability and rapid clearance contribute to the efficacy and improved systemic safety profile of ciclesonide.     

Ciclesonide: a novel inhaled corticosteroid

Inhaled corticosteroids (ICS) are a mainstay in the treatment of persistent asthma, a disease with increasing prevalence and cost implications worldwide. However, long-term use of currently available ICS is associated with local adverse effects that include hoarseness and oral candidiasis. In addition, systemic adverse effects including adrenal cortical suppression, osteoporosis, growth retardation, cataracts and glaucoma are also present. Ciclesonide is a novel ICS, which promises to provide airway anti-inflammatory efficacy that is comparable with that of the available ICS in addition to reducing the risk for local and systemic adverse events. Ciclesonide is an agent that is inactive until it reaches its target site, the lung, where it is converted to its active metabolite desisobutyryl-ciclesonide. In addition, other favourable pharmacokinetic and pharmacodynamic characteristics such as high protein binding, low oral bioavailability and rapid clearance contribute to the efficacy and improved systemic safety profile of ciclesonide.     

Fluticasone propionate: a potent inhaled corticosteroid for the treatment of asthma

Fluticasone propionate (FP) is a potent inhaled corticosteroid (ICS) for the treatment of asthma. It is currently marketed in both the United States (as Flovent) and Europe (as Flixotide). Fluticasone is available in both aerosolised metered dose inhaler (MDI) and dry powder devices, with dosages ranging from 44-500 micrograms/puff. FP has been extensively studied in both children and adults; efficacy has been documented across the entire spectrum of asthma severity, including corticosteroid-dependent disease. Clinical data with FP strongly corroborates the in vitro pharmacokinetic and pharmacodynamic studies that FP is at least twice as potent as beclomethasone dipropionate (BDP), budesonide (BUD) or triamcinolone acetonide (TAA). Both objective (lung function) and subjective (symptoms, beta-agonist use and quality of life) outcomes are improved with FP treatment. Extensive post-marketing surveillance with FP suggests that it is more cost-effective than BUD and flunisolide (FLU) when analysed by an overall healthcare cost perspective. Most of the benefits arise from decreased hospitalizations, emergency room visits and physician-office visits. Extensive safety data with FP documents no clinically meaningful effects on bone mass, nor impairment of growth velocity in children. Considering the efficacy and safety data along with the ability to optimise patient's asthma therapy using the delivery devices and strengths available, FP has become a leader in the ICS marketplace to date.     

Fluticasone propionate: a potent inhaled corticosteroid for the treatment of asthma

Fluticasone propionate (FP) is a potent inhaled corticosteroid (ICS) for the treatment of asthma. It is currently marketed in both the United States (as Flovent^®) and Europe (as Flixotide^®). Fluticasone is available in both aerosolised metered dose inhaler (MDI) and dry powder devices, with dosages ranging from 44 - 500 μg/puff. FP has been extensively studied in both children and adults; efficacy has been documented across the entire spectrum of asthma severity, including corticosteroid-dependent disease. Clinical data with FP strongly corroborates the in vitro pharmacokinetic and pharmacodynamic studies that FP is at least twice as potent as beclomethasone dipropionate (BDP), budesonide (BUD) or triamcinolone acetonide (TAA). Both objective (lung function) and subjective (symptoms, β-agonist use and quality of life) outcomes are improved with FP treatment. Extensive post-marketing surveillance with FP suggests that it is more cost-effective than BUD and flunisolide (FLU) when analysed by an overall healthcare cost perspective. Most of the benefits arise from decreased hospitalisations, emergency room visits and physician-office visits. Extensive safety data with FP documents no clinically meaningful effects on bone mass, nor impairment of growth velocity in children. Considering the efficacy and safety data along with the ability to optimise patient’s asthma therapy using the delivery devices and strengths available, FP has become a leader in the ICS marketplace to date.     

哮喘患儿吸入糖皮质激素的调查分析

目的：了解哮喘儿童吸入糖皮质激素应用情况。方法：对来咳喘专科就诊的患儿应用统一的调查表,内容包括吸入情况、发作情况、中断情况、再吸情况。结果：172例患者中有持续吸入史者仅28．5％,而其中仅44．9％坚持用药1年以上,停药后再用药有效。结论：实际应用情况不尽人意。     

The newly developed inhaled corticosteroid ciclesonide for the treatment of asthma

Ciclesonide is the most recently developed inhaled corticosteroid for the treatment of asthma to enter global markets. It has been formulated as an aerosol solution in a metered dose inhaler with hydrofluoralkane. The mass median aerodynamic diameter of aerosolised ciclesonide is 1 - 2 microm, providing excellent lung deposition characteristics. Ciclesonide can undergo reversible esterification in the lungs, possibly allowing once-daily dosing, and is highly protein bound, possibly leading to reduced systemic side effects. Clinical trials suggest that ciclesonide effectively controls asthma and has a favourable safety profile.     

The newly developed inhaled corticosteroid ciclesonide for the treatment of asthma

Ciclesonide is the most recently developed inhaled corticosteroid for the treatment of asthma to enter global markets. It has been formulated as an aerosol solution in a metered dose inhaler with hydrofluoralkane. The mass median aerodynamic diameter of aerosolised ciclesonide is 1 – 2 µm, providing excellent lung deposition characteristics. Ciclesonide can undergo reversible esterification in the lungs, possibly allowing once-daily dosing, and is highly protein bound, possibly leading to reduced systemic side effects. Clinical trials suggest that ciclesonide effectively controls asthma and has a favourable safety profile.     

Mometasone furoate dry powder inhaler: a once-daily inhaled corticosteroid for the treatment of persistent asthma

ABSTRACT

Background: Mometasone furoate (MF), a potent synthetic inhaled corticosteroid (ICS) with a high affinity for the glucocorticoid receptor, is approved for use in the treatment of asthma.

Scope: Publications reviewed in this article were identified via searches of MEDLINE and EMBASE databases using the terms ‘mometasone furoate AND pharmacology’ and ‘mometasone furoate AND asthma AND clinical trial’. Data from abstracts presented at respiratory society meetings, and relevant background information, are also reviewed.

Findings: In clinical studies, MF, administered by dry powder inhaler (MF-DPI), was effective in treating all severities of persistent asthma, improving pulmonary function, reducing asthma symptoms, and reducing or eliminating the need for oral corticosteroids. Once-daily dosing of MF-DPI was effective in patients with mild or moderate persistent asthma previously taking twice-daily regimens of inhaled corticosteroids (ICSs), and in patients taking only inhaled β₂?agonists for symptom relief. Once-daily dosing in the evening with MF-DPI 200?µg conferred a greater benefit than morning dosing with MF-DPI 200?µg. Patients with severe asthma who were dependent on oral corticosteroids (OCSs) and high doses of ICSs were able to achieve greater asthma control and reduce or even eliminate OCSs when switched to MF-DPI. In trials of up to 1 year in duration, MF-DPI was well tolerated, with the majority of adverse events considered mild or moderate in intensity. MF had low systemic bioavailability and no clinically significant hypothalamic–pituitary–adrenal-axis suppression at therapeutic doses. The DPI device is a multiple-dose inhaler with a counter containing agglomerates of MF and lactose. Patients of all severities of persistent asthma were able to generate and maintain airflow profiles necessary to provide a uniform and accurate dose.

Limitations: Only one study evaluated both morning and evening administration of once-daily doses, and one of the comparative clinical trials was an open-label study.

Conclusion: Once-daily administration of MF-DPI 200–400?µg in patients with mild to moderate persistent asthma effectively improved lung function and asthma control. In patients with severe persistent asthma dependent on oral corticosteroids, treatment with MF-DPI 400?µg BID permitted substantial reduction of oral corticosteroid use. All MF-DPI treatments were well tolerated and had minimal systemic effects.     

吸入性激素治疗哮喘的观察

目的：观察吸入性激素治疗支气管哮喘病人的效果。方法：56例轻、中度支气管哮喘患者，32例使用吸入性激素治疗4周。结果；吸入性激素治疗组在症状体征的改善，肺功能提高，减少合用β2-激动剂，减少副作用等方面均优于对照组。并且明显减少哮喘的发作次数，结论：吸入性激素是目前治疗支气管哮喘具有高效性和安全性的理想药物。     

Ciclesonide--a novel corticosteroid for the management of asthma

Ciclesonide (CIC) is a novel inhaled corticosteroid (ICS) approved by US Food and Drug Administration for the treatment of persistent asthma, available as a pressurized metered-dose inhaler in two strengths, 80 mcg/activation and 160 mcg/activation. Ciclesonide is a corticosteroid with unique pharmacological profile including a high degree of serum protein binding, a low oral bioavailability and rapid systemic elimination. Ciclesonide is a prodrug metabolized by esterases to desisobutyryl ciclesonide (des-CIC), an active metabolite with a 100-fold greater affinity for the glucocorticoid receptor. It has shown to improve pulmonary functions, reduce the need for oral corticosteroids (OCSs) and cause lesser suppression of the hypothalamic-pituitary-adrenal axis in asthmatic patients. Clinical efficacy studies suggest that Ciclesonide is superior to placebo and is at least as effective as several active comparators with an improved therapeutic margin thereby improving the therapeutic outcome in patients of asthma.     

An assessment of asthma exacerbations in pediatric patients using a long-acting B2-agonist plus inhaled corticosteroid versus an inhaled corticosteroid alone

BackgroundAn asthma exacerbation is an anticipated sudden worsening of the disease severity, which usually does not respond to conservative therapy. The management of asthma depends on the severity of the disease symptoms, which includes an inhaled corticosteroid (ICS) and a bronchodilator. This study aimed to assess the efficacy of combining a long-acting B2-agonist (LABA) with ICS, compared to ICS alone, to reduce the incidence of asthma exacerbations in pediatric patients, diagnosed with severe persistent asthma.MethodsA retrospective analysis of the medical records was conducted for 586 children, admitted to the Emergency Department (ED) at King Abdullah Specialized Children Hospital in Riyadh, Saudi Arabia, for the management of severe persistent asthma symptoms, from January 2016 to September 2019.ResultsThe majority (n = 480, 81.9%) of the patients received fluticasone (Flovent)® as the standard of care ICS treatment for controlling asthma, and a small proportion (n = 106, 18.1%) were treated with a combination of LABA and ICS. A significant increase in the frequency of recurrent asthma exacerbation episodes occurred in the group receiving ICS alone (98.5%), compared to 67.0% in the combination group (p < 0.0001). Moderate to severe exacerbations were significantly higher in the ICS group compared to the combination group (95.6% versus 84.5%, respectively, p = 0.0005).ConclusionsThe current results confirm the substantial efficacy of the LABA/ICS combination therapy in reducing the incidence and severity of asthma exacerbations in pediatric patients, compared to ICS alone.     

Ratio of inhaled corticosteroid to bronchodilator treatment and asthma hospitalisation

BACKGROUND: Previous research based on aggregated data has led to conflicting interpretations of the relationship between the corticosteroid:bronchodilator (C:B) ratio and outcome measures. OBJECTIVES: To assess whether the C:B ratio is associated with hospital contact for asthma at individual patient level. METHODS: The study was a retrospective multivariate analysis, using data from the U.K. General Practice Research Database from 1993 to 1996. The subjects were 3465 asthma-diagnosed patients receiving bronchodilator and corticosteroid medication. The main outcome measures were asthma-related hospital contacts. RESULTS: There was an inverse association between the C:B ratio and hospital contact after controlling for age. The odds ratio for the C:B ratio was 0.87 (95 % CI 0.73-0.98) and 1.04 (95% CI 1.01-1.07) for five-year agebands among patients aged five years and over. There was no systematic relationship between the C:B ratio and hospital contacts for patients aged under five years. CONCLUSION: The results of this study show that higher C:B ratios are associated with lower levels of hospital contacts at patient level, although there are exceptions possibly linked to disease severity. For patients under five years, the ratio may not be a good outcome measure, perhaps owing to the difficulty in diagnosing asthma or poor compliance.     

Ciclesonide and the treatment of asthma

Importance of the field: Asthma is a chronic disease characterized by airway inflammation and hyper-responsiveness. Inhaled corticosteroids (ICSs) constitute the guideline-recommended first-line therapy for persistent asthma. However, concerns regarding ICS-related adverse events may contribute to their underutilization by physicians and patients.

Areas covered in this review: The currently available published data on the pharmacokinetic and pharmacodynamic properties, safety and efficacy of the ICS, ciclesonide, is described. Peer-reviewed publications (1996 – 2009) on the pharmacodynamic and pharmacokinetic profile, safety and efficacy of ciclesonide were reviewed.

What the reader will gain: Ciclesonide is delivered as an inactive prodrug, which is cleaved to the active molecule by intracellular esterases located in the lungs. This and other pharmacodynamic and pharmacokinetic properties may limit the amount of active molecule outside the lung and may reduce the incidence of side effects. Randomized placebo-controlled studies found that ciclesonide can initiate and maintain disease control in subjects with persistent asthma of all disease severities. Moreover, studies have found that ciclesonide is as effective as other ICSs in establishing and controlling disease symptoms. Controlled clinical trials also showed that ciclesonide is associated with minimal systemic and local treatment-related adverse events.

Take home message: Published findings indicate that ciclesonide is effective at initiating and maintaining asthma control and is well tolerated, with a positive safety profile.     

Ciclesonide: a review of its use in the management of asthma

Ciclesonide (Alvesco) is an inhaled corticosteroid used in the preventative treatment of persistent bronchial asthma in adults, adolescents and, in some countries, children. The drug is delivered by a non-chlorofluorocarbon hydrofluoroalkane (HFA) metered-dose inhaler (MDI). In the lungs, ciclesonide is converted to an active metabolite, which is responsible for the beneficial effects of the drug in patients with asthma. Ciclesonide and its active metabolite have low systemic bioavailability and therefore have a low potential to produce systemic adverse events. Inhaled ciclesonide delivered by HFA-MDI is effective in the prophylactic treatment of persistent asthma in adults, adolescents and children, and is generally well tolerated. In general, ciclesonide improves lung function and reduces asthma symptoms and rescue medication use in adults and adolescents with asthma of varying severity. The drug is generally no less effective than other inhaled corticosteroids with regard to maintaining or improving lung function and may have a more favourable tolerability profile than some other agents in this class. Ciclesonide has also shown efficacy in paediatric patients with asthma. Data on its long-term effects on other clinical outcomes, such as asthma exacerbations, would be of interest. Further comparative and long-term studies would also be beneficial in order to definitively position ciclesonide with respect to other inhaled corticosteroids. In the meantime, ciclesonide offers an effective and well tolerated first-line preventative treatment option for persistent asthma.     

吸烟对支气管哮喘患者吸入糖皮质激素的影响

目的探讨吸烟对支气管哮喘患者吸入糖皮质激素(ICS)疗效的影响。方法对不吸烟(15例)及吸烟(15例)的支气管哮喘患者每日吸入布地奈德治疗,必要时可吸入β2受体激动剂。治疗4周,治疗前后进行肺功能测定。结果不吸烟组患者治疗后的清晨PEF、睡前PEF、FEV1%均较治疗前改善(P<0.05)。而吸烟组患者在治疗前后上述指标却变化不大(P>0.05)。结论吸烟降低了哮喘患者对ICS的治疗反应性,对吸烟的哮喘患者,治疗可能需要特殊的调整。     

支气管扩张合并支气管哮喘患者表面激素吸入的安全性及疗效观察

目的探讨支气管扩张合并支气管哮喘患者表面激素吸入的安全性及疗效观察。方法将2016年2月~2017年2月在我院呼吸内科治疗的86例支气管扩张合并支气管哮喘患者随机分为两组,对照组给予常规西医对症治疗,在此基础上观察组给予二丙酸倍氯米松(必可酮)雾化吸入治疗,比较两组患者的临床疗效、肺功能改善情况、血常规变化、气道高反应性变化。结果观察组临床有效率为93.02%,明显高于对照组的74.42%,两组间有统计学差异(P<0.05);观察组治疗后FEV1、PEF、FVC、FEV1/FVC较对照组明显好转,两组间有统计学差异(P<0.05);观察组治疗后白细胞计数、中性粒细胞、淋巴细胞、嗜酸粒细胞均较对照组明显降低,两组间有统计学差异(P<0.05);观察组治疗后气道阻力(Raw)、气道传导率(Gaw)、气道高反应性(BHR)较对照组明显改善,两组间有统计学差异(P<0.05)。结论支气管扩张合并支气管哮喘患者表面激素吸入治疗有良好效果,能显著改善气道炎性反应,增强肺通气功能,降低气道阻力和高反应性,且不良反应少,具有积极的临床意义。     

Ciclesonide in persistent asthma: the evidence of its therapeutic value

INTRODUCTION: Asthma, a respiratory disease associated with airway inflammation and hyperresponsiveness, is one of the most prevalent chronic diseases worldwide affecting both children and adults. Inhaled corticosteroids are considered to be the cornerstone of asthma management. Ciclesonide, an airway-activated inhaled corticosteroid, has been developed for the management of persistent asthma. Its once-daily administration and airway activation may be advantageous in the treatment of asthma. AIMS: The purpose of this article is to review the place in therapy of ciclesonide in the management of patients with persistent asthma based on the available clinical evidence. EVIDENCE REVIEW: The available evidence indicates that ciclesonide has an effect on pulmonary function (forced expiratory volume in 1 s, forced vital capacity, and peak expiratory flow), as well as producing improvements in patient-reported symptoms that are equivalent to those achieved with other inhaled corticosteroids. A few studies have focused on health-related quality of life and have demonstrated a positive effect with ciclesonide treatment. Its pharmacokinetic profile may offer advantages in terms of adverse effects, both local and systemic, although most of the data come from 12-week studies. PLACE IN THERAPY: The current evidence shows that ciclesonide offers another alternative among inhaled corticosteroids, with the potential for fewer adverse effects. The unique pharmacokinetic profile of ciclesonide allows once-daily administration and the airway activation of the drug appears to confer clinical benefit in the treatment of asthma. Its lack of systemic adverse effects make it a viable option for pediatric use.