Ciclesonide

Ciclesonide: A Pro-Soft Drug Approach for Mitigation of Side Effects of Inhaled Corticosteroids.[Pubmed:27339407]

J Pharm Sci. 2016 Sep;105(9):2509-2514.

Inhaled corticosteroids are used as one of the first-line drug therapy in patients with asthma. However, their long-term use is associated with various oropharyngeal and systemic side and adverse effects. Design of pro-soft drug is one of the strategies, which was adopted in the design of Ciclesonide for mitigation of side effects usually observed with the use of inhaled corticosteroids. Ciclesonide, a pro-soft drug, is converted to an active metabolite desisobutyryl-Ciclesonide in the lungs. The anti-inflammatory effect of desisobutyryl-Ciclesonide is much higher than Ciclesonide, and therefore, the local effect of the metabolite is higher with lower systemic side effects. Ciclesonide has favorable pharmacokinetic and pharmacodynamic properties as inhaled corticosteroid including low oral bioavailability, high plasma protein binding and rapid systemic clearance, high pulmonary deposition and distribution and long pulmonary residence duration. These advantageous properties make Ciclesonide a very effective treatment option with low side effects. Various clinical studies support safety and efficacy of Ciclesonide use in mild, moderate, and severe asthma patients.

Control of moderate-to-severe asthma with randomized ciclesonide doses of 160, 320 and 640 mug/day.[Pubmed:28331346]

J Asthma Allergy. 2017 Mar 7;10:35-46.

BACKGROUND: The inhaled corticoteroid (ICS) Ciclesonide (Cic), controls asthma symptoms in the majority of patients at the recommended dose of 160 microg/day. However, the relationship between the level of asthma control and increasing doses of Cic is unknown. This study investigated whether long-term treatment with higher doses of Cic would further improve asthma symptoms in patients with uncontrolled asthma despite ICS use. PATIENTS AND METHODS: In a double-blind, randomized, parallel-group study, 367 patients were allocated to one of three treatment arms (Cic 160, 320 and 640 microg/day). After a single-blind, 3-week baseline period with Cic 160 microg/day, eligible patients were randomized to receive 52 weeks of treatment with Cic 160, 320 or 640 microg/day (double-blind period) during which forced expiratory volume in 1 second (FEV1), exacerbations and Asthma Control Questionnaire (ACQ) scores were measured. RESULTS: Treatment with all the three doses was associated with significant improvements in ACQ scores, FEV1 and asthma symptoms (P<0.01). There were no statistically significant differences between the three doses. The results of the primary end point analysis showed a numerical improvement in the ACQ score with Cic 640 microg/day compared with Cic 160 microg/day (least square [LS] mean: -0.122; two-sided P-value: 0.30). Post hoc subgroup analyses showed that the improvement in the ACQ score with Cic 640 microg/day compared with Cic 160 microg/day was statistically significant in subjects who experience at least one exacerbation per year (LS mean: -0.586; 95% confidence interval: -1.110, -0.062, P=0.0285). Adverse events were low and consistent with the known safety profile of Cic. CONCLUSION: In patients with persistent, uncontrolled asthma, increasing the Cic dose from 160 to 640 microg/day provided no clear additional effect. Patients who experience more than one exacerbation per year may benefit from higher doses; however, further studies are necessary to confirm this. All Cic doses were well tolerated.

Asthma-Related Outcomes in Patients Initiating Extrafine Ciclesonide or Fine-Particle Inhaled Corticosteroids.[Pubmed:28102056]

Allergy Asthma Immunol Res. 2017 Mar;9(2):116-125.

PURPOSE: Extrafine-particle inhaled corticosteroids (ICS) have greater small airway deposition than standard fine-particle ICS. We sought to compare asthma-related outcomes after patients initiated extrafine-particle Ciclesonide or fine-particle ICS (fluticasone propionate or non-extrafine beclomethasone). METHODS: This historical, matched cohort study included patients aged 12-60 years prescribed their first ICS as Ciclesonide or fine-particle ICS. The 2 cohorts were matched 1:1 for key demographic and clinical characteristics over the baseline year. Co-primary endpoints were 1-year severe exacerbation rates, risk-domain asthma control, and overall asthma control; secondary endpoints included therapy change. RESULTS: Each cohort included 1,244 patients (median age 45 years; 65% women). Patients in the Ciclesonide cohort were comparable to those in the fine-particle ICS cohort apart from higher baseline prevalence of hospitalization, gastroesophageal reflux disease, and rhinitis. Median (interquartile range) prescribed doses of Ciclesonide and fine-particle ICS were 160 (160-160) mug/day and 500 (250-500) mug/day, respectively (P<0.001). During the outcome year, patients prescribed Ciclesonide experienced lower severe exacerbation rates (adjusted rate ratio [95% CI], 0.69 [0.53-0.89]), and higher odds of risk-domain asthma control (adjusted odds ratio [95% CI], 1.62 [1.27-2.06]) and of overall asthma control (2.08 [1.68-2.57]) than those prescribed fine-particle ICS. The odds of therapy change were 0.70 (0.59-0.83) with Ciclesonide. CONCLUSIONS: In this matched cohort analysis, we observed that initiation of ICS with Ciclesonide was associated with better 1-year asthma outcomes and fewer changes to therapy, despite data suggesting more difficult-to-control asthma. The median prescribed dose of Ciclesonide was one-third that of fine-particle ICS.