Ciclesonide versus placebo for chronic asthma in adults and children

In asthma, inflammation (swelling in the wall) narrows the airway and is the main factor giving rise to asthmatic symptoms of cough, wheeze, shortness of breath and chest tightness. Inhaled corticosteroids (ICS) which are given usually more than once daily are now recommended as first line therapy for most people with asthma. The currently available ICS, such as budesonide (BUD), beclomethasone (BDP) or fluticasone (FP), have been available for many years and have proven to be an important therapy for controlling inflammation and symptoms. However, these drugs can be associated with significant side-effects, especially local effects in the upper airways such as hoarseness and oral candida (thrush infection). The main reputed advantage of ciclesonide (CIC, a new generation of ICS), is its ability not only (as with other ICS) to be delivered locally by inhalation but specifically to the lower airways of the lung in a form which potentially minimises local side-effects. Overall this advantage of CIC could lead to a reduction of local airway side-effects with once daily therapy and thereby improving adherence to therapy. The results from this review indicate that CIC at low to moderate doses improves lung function and reduces asthma symptoms compared to placebo, but the short duration of the studies means that there is a lack of information about the impact on asthma exacerbations. Thus the currently recommended doses of CIC of 100-200 mcg daily would seem appropriate. However, the number of studies in the higher dose range are low and further studies are therefore required in adults and children to determine whether higher CIC doses will give significant benefit without increasing adverse events. It will also be important to determine in clinical studies how CIC compares to the other currently available ICS in terms of efficacy and safety in asthmatic adults and children in order to determine the precise role of CIC therapy in asthma. The published data are insufficient to assess the reputed safety advantage of ciclesonide, and better assessment and reporting in studies is required to address this important question.

Authors' conclusions: 

Ciclesonide was more effective than placebo, in the short term, in improving lung function in patients with mild to moderate asthma previously treated with inhaled corticosteroids. There remain questions as to dose response, and the lack of data on the longer term impact on exacerbations and safety profile should be addressed in future studies.

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Background: 

Inhaled corticosteroids are an integral part of asthma management, and act as an anti-inflammatory agent in the airways of the lung. These agents confer significant benefit in terms of symptom management and improvement in lung function, but may also cause harm in terms of local and systemic side-effects. Ciclesonide is a novel steroid that has efficient distribution and release properties that mean it can be taken once daily, making it potentially useful in ongoing asthma management.

Objectives: 

To assess the efficacy of inhaled ciclesonide in adults and children with chronic asthma.

Search strategy: 

We searched the Cochrane Airways Group register of trials with pre-defined terms. Additional searches of CENTRAL and PubMed were undertaken. The literature searches for this review are current up to June 2007.

Selection criteria: 

Randomised parallel or crossover studies were eligible for the review. We included studies comparing ciclesonide with placebo, and we also included studies comparing ciclesonide at different doses.

Data collection and analysis: 

Two authors assessed studies for inclusion in the review, extracted data independently and checked each others' work. We contacted study investigators in order to obtain additional data. Extracted data were entered into RevMan 4.2 and analysed as fixed effect mean differences for continuous data, and fixed effect risk ratios for dichotomous data.

Main results: 

Eighteen trials (reporting 20 study comparisons) met the review entry criteria. We report findings from 18 group comparisons where data were available (6343 participants, of whom 1692 were children).

Ciclesonide versus placebo: The short duration of the included studies means that there is a lack of data with respect to the impact of ciclesonide on asthma exacerbations. At doses of 100 mcg/d or less up to 400 mcg/d in mild to moderate asthma, ciclesonide improved lung function, asthma symptoms and rescue inhaler use, compared with placebo.

Dose response outcomes: Comparisons of 100 versus 200 mcg/d, 100 versus 400 mcg/d and 400 versus 800 mcg/d did not yield significant differences in lung function outcomes.
Adverse event data were not available in sufficient detail to permit assessment of the safety profile of this drug.

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