Control of moderate-to-severe asthma with randomized ciclesonide doses of 160, 320 and 640 μg/day.
BACKGROUND
The inhaled corticoteroid (ICS) ciclesonide (Cic), controls asthma symptoms in the majority of patients at the recommended dose of 160 µg/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.


METHODS
In a double-blind, randomized, parallel-group study, 367 patients were allocated to one of three treatment arms (Cic 160, 320 and 640 µg/day). After a single-blind, 3-week baseline period with Cic 160 µg/day, eligible patients were randomized to receive 52 weeks of treatment with Cic 160, 320 or 640 µg/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, FEV1and 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 µg/day compared with Cic 160 µg/day (least square [LS] mean: -0.122; two-sidedP-value: 0.30). Post hoc subgroup analyses showed that the improvement in the ACQ score with Cic 640 µg/day compared with Cic 160 µg/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.


CONCLUSIONS
In patients with persistent, uncontrolled asthma, increasing the Cic dose from 160 to 640 µg/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.
Pediatric Research Unit, Kolding Hospital, University of Southern Denmark, Kolding, Denmark.
Søren E
SE
Pedersen
Vertex, Phase IV & Global Strategy, London, UK.
Niyati
N
Prasad
Vifor Pharma Ltd, Clinical Research & Biometrics, Glattbrugg, Switzerland.
Udo-Michael
UM
Goehring
Swedish Social Insurance Agency, Government Offices of Sweden, Stockholm, Sweden.
Henrik
H
Andersson
Department of Pulmonology, Griac Research Institute, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Dirkje S
DS
Postma
asthma control; dose-response