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Original Research: ASTHMA |

Comparison of the Effect of Low-Dose Ciclesonide and Fixed-Dose Fluticasone Propionate and Salmeterol Combination on Long-term Asthma Control FREE TO VIEW

Dirkje S. Postma, MD, PhD; Paul M. O’Byrne, MBBCh, FCCP; Søren Pedersen, MD, PhD
Author and Funding Information

From the University Medical Center Groningen (Dr Postma), University of Groningen, Groningen, The Netherlands; McMaster University (Dr O’Byrne), Hamilton, ON, Canada; and University of Odense (Dr Pedersen), Kolping, Denmark.

Correspondence to: Dirkje S. Postma, MD, PhD, Department of Pulmonary Diseases, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands; e-mail: d.s.postma@long.umcg.nl


Funding/Support: This study was funded by Nycomed.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2011 American College of Chest Physicians


Chest. 2011;139(2):311-318. doi:10.1378/chest.09-1735
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Background:  Patients with mild persistent asthma constitute about 70% of the asthma population; thus, it is important to know which first-line treatment is best for the management of mild asthma. We compared benefits of first-line treatment with ciclesonide and a combination of fluticasone and salmeterol in patients with mild asthma.

Methods:  Patients aged 12 to 75 years with mild persistent asthma were enrolled in a randomized, double-blind, placebo-controlled study. After run-in, patients were randomized to ciclesonide 160 μg once daily (CIC160), fluticasone propionate/salmeterol 100/50 μg bid (FP200/S100), or placebo for 52 weeks. The primary variable was time to first severe asthma exacerbation; the coprimary variable was the percentage of poorly controlled asthma days. Patients recorded asthma symptoms and salbutamol use in electronic diaries and completed a standardized version of the Asthma Quality of Life Questionnaire.

Results:  Compared with placebo, the time to first severe asthma exacerbation was prolonged, and lung function was improved with FP200/S100 treatment (P = .0002) but not with CIC160. Both CIC160 and FP200/S100 provided significantly fewer poorly controlled asthma days than placebo (P ≤ .0016 for both active treatments). Moreover, both active treatments provided significantly more asthma symptom-free days (P ≤ .0001), rescue medication-free days (P = .0005, one-sided), and days with asthma control (P ≤ .0033). Overall Asthma Quality of Life Questionnaire scores were significantly higher in both active treatment groups than placebo (P ≤ .0017).

Conclusions:  In mild asthma, FP200/S100 prolonged time to first severe asthma exacerbation, and CIC160 and FP200/S100 were clinically equieffective for most measures of asthma control.

Trial registry:  ClinicalTrials.gov; No.: NCT00163358; URL: www.clinicaltrials.gov

Figures in this Article

Asthma is an inflammatory airway disease that can vary clinically from mild intermittent to persistent severe disease. Patients with mild persistent asthma constitute a significant proportion (up to 70%) of the asthma population1; thus, it is important to know which first-line treatment is best for the management of mild asthma. Asthma guidelines have regarded persistent asthma to be mild if asthma symptoms occur more than weekly but less than daily, nocturnal symptoms occur less than weekly, and patients have normal lung function (FEV1 or peak expiratory flow [PEF] > 80%) between asthma episodes.2,3 Because asthma severity may change over time, asthma classification and treatment is now based on achieving asthma control.3

The aim of asthma control is not only to control symptoms but also to achieve the best possible lung function, prevent exacerbations, and maintain normal daily activities with the lowest possible treatment dose and minimal short- and long-term adverse effects. To achieve this aim, long-term treatment generally is prescribed. Many studies have investigated which treatment is the most effective for controlling asthma, yet only a few have addressed this in mild asthma.4-10 Older studies generally included a minority of patients with mild asthma when stating that they investigated treatment in mild to moderate asthma, as reflected by a mean FEV1 usually around 70% predicted of normal and rescue β2-agonist use of 2 to 3 puffs/d.11,12

Antiinflammatory therapy is the cornerstone of asthma treatment, and mild asthma can be effectively controlled with low-dose inhaled corticosteroids (ICSs).8,9 Several studies have shown that in moderate and severe asthma, the combination of an ICS and a long-acting β2-agonist (LABA) provides superior asthma control, better lung function, and fewer exacerbations than doubling the ICS dose.13,14 The few studies addressing this issue in patients with mild asthma suggest that the two treatment modalities have very similar clinical effects.9,15

Ciclesonide is an ICS with pharmacologic properties that enable once-daily dosing.4,7,16 Moreover, it has been shown to be associated with only minor side effects and particularly little or no cortisol suppression.17,18 The current study investigated how patients with mild asthma benefit from first-line treatment with once-daily, low-dose ciclesonide treatment compared with fixed, low-dose fluticasone and salmeterol bid.

Patients

Patients aged 12 to 75 years were included if they were given a clinical diagnosis of mild persistent asthma (FEV1 ≥ 80% predicted at least 4 h after rescue medication use; only short-acting β-agonists as required for 2 months before the start of the study). They were randomized to treatment if after a 2-week run-in period, they had an FEV1 ≥ 80% predicted, reversible airway obstruction (change in FEV1 ≥ 12% or ≥ 200 mL) after 200 to 400 μg salbutamol inhalation, limited use of rescue medication (not every day during run-in), no nocturnal asthma symptoms, and a total daytime asthma symptom score of > 2 and < 10. Exclusion criteria included an asthma exacerbation or systemic steroid use within 2 months prior to the run-in period, hypersensitivity to ICS, intolerance of short-acting β-agonists, initiation of immunotherapy, COPD, current- and ex-smoking (≥ 10 pack-years) status, and suspicion of noncompliance.

Study Design

This randomized, double-blind, double-dummy, placebo-controlled, parallel-group study was conducted over 52 weeks, with an additional 2-week run-in period, in 98 research centers worldwide (e-Appendix 1). Patients visited research centers up to two times during a 2-week run-in period, and at 1, 2, 4, 6, 8, 10, and 12 months.

During run-in, patients were treated with salbutamol as rescue medication only. Following run-in, patients were randomized (1:1:1) to ciclesonide 160 μg once daily (CIC160) in the afternoon, fluticasone propionate/salmeterol 100/50 μg bid (FP200/S100), or placebo. Each medication was administered through a metered-dose inhaler, using 1,1,1,2-hydrofluoroalkane as a propellant. Salbutamol was used throughout the study period, as needed. No ICSs or LABAs other than study medications were permitted for 2 months prior to randomization and the 12-month study period.

The ethics committees of the individual investigators’ affiliations approved the protocol. All participants provided written informed consent.

Efficacy Measurements:

The time to the first severe asthma exacerbation was the primary efficacy variable and defined as a > 30% decrease in PEF from baseline on 2 consecutive days or the need for oral corticosteroids, hospitalization, or emergency treatment of worsening asthma.9 Following an exacerbation, patients were treated with an additional 7-day course of oral corticosteroids (0.5 mg/kg body weight). All exacerbations were recorded as adverse events (AEs) on patient case report forms. Patients who experienced two severe asthma exacerbations were withdrawn. The percentage of poorly controlled asthma days was the coprimary variable and defined as rescue medication use two or more times above the mean value during run-in or the occurrence of a nocturnal awakening due to asthma.

Patients recorded daily in an electronic diary their daytime asthma symptoms (rating 0-4, with 0 = very well, no symptoms, and 4 = asthma very bad, unable to carry out daily activities as usual), nighttime asthma symptoms (rating 0-4, with 0 = no symptoms and 4 = bad night, awake most of the night because of asthma),9 and salbutamol use. Diary data were recorded with an electronic asthma monitor (AM2; VIASYS; Höchberg, Germany) that captured the time and date of data entry. Additionally, patients recorded the highest of three PEF readings in the morning (after waking) and between 6:00 and 8:00 pm before inhalation of study medication and not within 4 h after the last use of rescue medication.

FEV1 measurements were performed between 6:00 and 10:00 am (within ± 1.5 h of the measurement at the first visit) on each clinic visit. Measurements were taken, and predicted values were according to the American Thoracic Society guidelines19 after withholding rescue medication for ≥ 4 h and prior to administration of study medication.

Quality of Life and Safety Measurements:

A standardized version of the Asthma Quality of Life Questionnaire (AQLQ[S]) was completed by patients during run-in and at 4, 8, and 12 months or at study termination. Score changes of ≥ 0.5 within the treatment period were considered clinically meaningful.20 Safety was assessed by AE reporting and oropharyngeal inspection.

Statistical Analysis

The primary efficacy variable—time to first severe asthma exacerbation—was analyzed by a one-sided log-rank test at the 0.025 level of significance. The analysis of the primary efficacy variable was defined as the first test of the confirmatory testing strategy. If superiority of CIC160 treatment vs placebo was not shown (ie, the null hypothesis for the first confirmatory test was not rejected) the confirmatory testing procedure ended as defined a priori. All further tests were performed in an exploratory manner.

The probability of not experiencing an asthma exacerbation was estimated using Kaplan-Meier analysis. Survival analyses of severe asthma exacerbations were performed using the log-rank test. Cox proportional hazard models were applied as supportive analyses. The coprimary variable—the number of poorly controlled asthma days—was analyzed using the Mann-Whitney U test for between-treatment differences. The key secondary variable was the percentage of asthma symptom-free days as measured over the whole treatment period. Between-group comparisons of asthma symptom scores, rescue medication use, and percentage of asthma symptom- and rescue medication-free days were performed using the Mann-Whitney U test.21 Nonparametric within-group comparisons of these variables were made using the Pratt modified Wilcoxon signed rank test. Other secondary variables, including FEV1, PEF, and AQLQ(S) domains and overall scores, were tested in an exploratory manner with an analysis of covariance model. Safety variables are presented with descriptive statistics. For within- and between-treatment differences, two-sided 95% CIs are provided. Two-sided P values are given for within-treatment differences, and between-treatment differences are presented as one-sided or two-sided P values.

All analyses were based on total, safety, full analysis, or valid patient case sets defined in accordance with the International Conference on Harmonization E9 guideline of 1998. The full analysis set was as close to the intention-to-treat (ITT) ideal as possible. Patients not receiving any double-blind study treatment were excluded from the full-analysis set. The valid cases set included patients who had participated in the study as intended (per protocol) and incorporated those who withdrew from the study as a result of a severe AE. Analyses of superiority were conducted based on the ITT population. Per treatment arm, 210 randomized patients were required to ensure a power of 90% in detecting a difference in the probability of not experiencing a severe asthma exacerbation of 0.80 (active treatment) and 0.65 (placebo) at the end of treatment (assuming a constant hazard ratio over time).

Patients

In total, 1,432 patients were enrolled, and 657 were randomized to treatment (CIC160, 212; FP200/S100, 223; placebo, 222). Five randomized patients did not receive study medication and were excluded from the ITT (Fig 1) and safety analyses. Demographic and baseline characteristics were comparable among all treatment groups (Table 1). At randomization, FEV1 was > 95% predicted in all groups. A total of 147 randomized patients (CIC160, 44 [20.8%]; FP200/S100, 42 [18.8%]; placebo, 61 [27.5%]) withdrew early from the study, the main reasons being the occurrence of AEs (CIC160, 24; FP200/S100, 12; placebo, 38) and the predefined withdrawal criterion (CIC160, 20; FP200/S100, 10; placebo, 32).

Figure Jump LinkFigure 1. Diagram of patient disposition. CIC160 = ciclesonide 160 μg once daily; FP200/S100 = fluticasone propionate/salmeterol 100/50 μg bid.Grahic Jump Location
Table Graphic Jump Location
Table 1 —Patient Baseline and Demographic Characteristics (Intention-to-Treat Population)

Data are presented as mean ± SD, unless otherwise indicated. AQLQ(S) = standardized version of the Asthma Quality of Life Questionnaire; CIC160 = ciclesonide 160 μg once daily; FP200/S100 = fluticasone propionate/salmeterol 100/50 μg bid.

a 

Data shown are from 14 d before baseline.

Efficacy Measurements
Time to First Exacerbation:

The time to first severe asthma exacerbation did not show superiority for CIC160 vs placebo (P = .24); therefore, the confirmatory testing procedure ended, and remaining analyses were conducted in an exploratory manner. The time to onset of the first severe asthma exacerbation showed superiority of FP200/S100 vs placebo (P = .0002). The probability of not experiencing a severe asthma exacerbation was 0.65 in the placebo group, 0.70 in the CIC160 group, and 0.82 in the FP200/S100 treatment group (Fig 2). The risk of a first severe asthma exacerbation was reduced by 19% by CIC160 vs placebo (P = .23). FP200/S100 significantly reduced the risk of experiencing a severe exacerbation vs placebo (P = .0002) and CIC160 (P = .01).

Figure Jump LinkFigure 2. Kaplan-Meier plot showing time to first exacerbation (intention-to-treat analysis). See Figure 1 legend for expansion of abbreviations.Grahic Jump Location
Percentage of Poorly Controlled Asthma Days:

Patients in the CIC160 and FP200/S100 treatment groups experienced significantly fewer poorly controlled asthma days than placebo-treated patients (P ≤ .0016, one-sided for both) (Table 2), without a significant difference between active treatments. The median number of days per year with poor control was 6.2 with placebo and 1.8 and 1.5 with FP200/S100 and CIC160, respectively.

Table Graphic Jump Location
Table 2 —Between- and Within-Treatment Differences for Coprimary and Secondary Variables at End of Study (Intention-to-Treat Population)

N/A = not applicable; PEF = peak expiratory flow. See Table 1 legend for expansion of other abbreviations.

a 

Least squares analysis.

Asthma Symptoms, Rescue Medication Use, and Asthma Control:

The median percentages of asthma symptom-free days were significantly different with CIC160 and FP200/S100 vs placebo (all P ≤ .0001) (Table 2), without a significant difference between the active treatment groups (P > .05).The median number of days per year without asthma symptoms was 17.5 with placebo, 23 with FP200/S100, and 31 with CIC160. Both active treatments provided significantly more asthma symptom-free days than placebo (P ≤ .008, one-sided), rescue medication-free days (P = .0005, one-sided), and days with asthma control (P ≤ .003, one-sided), without significant differences between the active treatment groups (Fig 3).

Figure Jump LinkFigure 3. Percentage of patients with asthma symptom-free days, rescue medication-free days, and asthma control days at the end of the treatment period. Asthma symptom-free days and asthma control days are the last 28 days before the last visit; rescue medication-free days are the week before the last visit. *P < .01, one-sided, vs placebo. †P < .001, one-sided, vs placebo. See Figure 1 legend for expansion of abbreviations.Grahic Jump Location

Asthma symptom scores decreased in all groups (Table 2), with reductions with CIC160 and FP200/S100 being significantly greater than with placebo (CIC160, P = .0015, one-sided; FP200/S100, P = .0007, one-sided). Similarly, both CIC160 (P = .0001, one-sided) and FP200/S100 (P = .0005, one-sided) significantly reduced salbutamol use compared with placebo, without a significant difference seen between CIC160 and FP200/S100.

Pulmonary Function, Quality of Life, and Safety Measurements:

Between-treatment differences in the change in FEV1 and PEF were significant for FP200/S100 vs placebo only (P < .0001, one-sided) (Table 2). Overall AQLQ(S) scores significantly increased in the CIC160 and FP200/S100 groups (P < .0001 for both) (Fig 4), compared with placebo (P ≤ .0017, one sided) (Table 2). Between-treatment comparison showed that the change in AQLQ(S) score was higher with CIC160 than with FP200/S100 (P < .0001, one-sided) (Table 2). AEs were mainly of mild or moderate intensity and were reported in 73.6% (n = 162), 73.3% (n = 154), and 64.0% (n = 142) of patients treated with placebo, CIC160, and FP200/S100, respectively. The most frequently reported AEs were asthma exacerbations, nasopharyngitis, and pharyngitis (Table 3).

Figure Jump LinkFigure 4. A, Least squares mean change in overall standardized asthma quality of life from baseline to study end (intention-to-treat population). B, Percentage of patients who showed an improvement in AQLQ(S) score ≥ 0.5 (intention-to-treat population). Least squares mean at baseline was 5.82 for all treatment groups. *P ≤ .0017, one-sided, vs placebo. AQLQ(S) = standardized version of the Asthma Quality of Life Questionnaire. See Figure 1 legend for expansion of other abbreviations.Grahic Jump Location
Table Graphic Jump Location
Table 3 —Frequently Reported Adverse Events in the Safety Population (≥ 5% of Patients in Any Treatment Group)

Data are presented as No. (%). See Table 1 legend for expansion of abbreviations.

The results of this 12-month study suggest that although only FP200/S100 increased time to the first exacerbation, CIC160 achieved similar levels of daily asthma control as FP200/S100 compared with placebo in patients with mild persistent asthma. Similar improvements were seen in poorly controlled asthma days, percentage of asthma symptom- and rescue medication-free days, percentage of days with asthma control, salbutamol use, asthma symptoms and AQLQ(S) scores with the two active treatments. In addition, FP200/S100 improved FEV1 and PEF compared with placebo.

The greater improvements in pulmonary function with FP200/S100 were expected given the bronchodilation provided by the LABA and findings in earlier studies.9,13,22,23 However, the improvement of near-normal lung function (ie, FEV1 values of 96% predicted in this study) may be less important than the improvements in asthma symptoms, rescue medication need, and asthma control. The difference between the two active treatments in time to first asthma exacerbation was at variance with findings of the Optimal Treatment of Mild Asthma (OPTIMA) trial, which compared the effects of adding an LABA (formoterol 4.5 μg bid) to budesonide (100 μg bid) for 1 year in patients with mild asthma (n = 698) who were steroid naïve or used ICS for < 3 months.9 In OPTIMA, the addition of formoterol improved lung function but not the occurrence of exacerbations. The rate of severe exacerbations was 0.77 per year in the placebo group, which was higher than anticipated in patients with mild asthma. Exacerbation rates were significantly lower in the budesonide group (0.29 exacerbations/y), and no additional benefit was seen with the combination (0.34 exacerbations/y). In addition, a recent study investigated patients with asthma who were stable on 100 μg fluticasone bid.15 After continuation of the same treatment or fluticasone 100 μg combined with salmeterol (50 μg) once daily for 16 weeks, time to treatment failure (the primary outcome) was similar between the two treatments (20.2 and 20.4%, respectively).

The reason for the discrepancy between the previous studies and the current study is unknown. Compared with OPTIMA,9 the patients included in the present study had comparable asthma severity and control at baseline (ie, FEV1 values of 90% predicted in the OPTIMA study vs 96% predicted in the current study) and percentages of patients with asthma symptom-free days of 60% and 61%, respectively. Moreover, the definition of an asthma exacerbation was comparable in the two studies. The only difference at baseline appeared to be that the use of rescue medication was lower in the current study (0.48 inhalations/d) vs the OPTIMA trial (0.90 inhalations/d). As for OPTIMA, the rate of severe exacerbations in the placebo group in the current study (1.16 exacerbations/y) was higher than expected for patients with mild asthma.

It seems unlikely that the once-daily dosage of ICS in the present study would have caused the difference seen in the time to first asthma exacerbation because several studies have shown clinical benefits, including reduced exacerbation rates in patients with mild to moderate asthma, with ciclesonide once daily.4,5,7,10 Moreover, once-daily ciclesonide has shown consistent and comparable clinical efficacy with other ICSs, including budesonide24,25 and fluticasone propionate,5,10,26 in improving pulmonary function, controlling asthma symptoms, and reducing rescue medication use and exacerbations.

We acknowledge that mild symptoms may not equate mild pathophysiology. For instance, a similar group of subjects with mild asthma and documented exercise-induced bronchoconstriction benefited more from a higher dose of ciclesonide once daily (320 μg).27 Thus, for some of these subjects with normal lung function, a higher dose of the relatively safe ICS ciclesonide may constitute an alternative to combining an ICS with an LABA.

In the current study, most outcome measures showed similar results for both the CIC160 and FP200/S100 groups. Indeed, similar improvements were seen in poorly controlled asthma days, percentage of asthma symptom- and rescue medication-free days, percentage of days with asthma control, salbutamol use, asthma symptoms, and AQLQ(S) scores with the two treatments. This finding indicates that the majority of patients with mild asthma can achieve satisfactory asthma control with ICS monotherapy without the need to administer multiple medications, which is convenient to patients. Further, it is in line with current asthma guidelines that recommend ICS monotherapy as the preferred first-line treatment and to add an LABA only if patients fail to achieve control with ICS monotherapy.3 The present study shows that in mild asthma, this treatment approach will delay a severe exacerbation. In addition, once an LABA has been added and asthma control achieved for > 3 months, Global Initiative for Asthma (GINA) guidelines recommend a reduction in treatment to the minimal amount that maintains asthma control,3 which may mean stepping back from combination therapy to monotherapy.

In conclusion, as a first-line approach in mild asthma, CIC160 monotherapy offered similar clinical benefits to FP200/S100 for a large number of measures of asthma control. Combination therapy may be required in some patients to attain full benefits for reducing exacerbations.

Author contributions:Dr Postma: contributed to the original concept of the study; study design; acquisition, analysis, and interpretation of data; drafting and revision of the manuscript for important intellectual content; and approval of the final version of the manuscript to be published.

Dr O’Byrne: contributed to the original concept of the study; study design; acquisition, analysis, and interpretation of data; drafting and revision of the manuscript for important intellectual content; and approval of the final version of the manuscript to be published.

Dr Pedersen: contributed to the original concept of the study; study design; acquisition, analysis, and interpretation of data; drafting and revision of the manuscript for important intellectual content; and approval of the final version of the manuscript to be published.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Postma has participated over the past 4 years in consultancy activities for AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and Nycomed and has received lecture fees from AstraZeneca, GlaxoSmithKline, Chiesi, and Nycomed. She has received grants-in-aid for research studies from AstraZeneca, GlaxoSmithKline, and Nycomed. Dr O’Byrne has been on advisory boards for AstraZeneca, Biolipox, GlaxoSmithKline, Merck, Nycomed, Topigen, Resistentia, and Wyeth and has received lecture fees from these and other pharmaceutical companies, including Chiesi and Ono Pharma. In addition, he has received grants-in-aid for research studies from AstraZeneca, Boehringer Ingelheim, Genentech, GlaxoSmithKline, Medimmune, Merck, Pfizer, and Wyeth. Dr Pedersen has participated over the past 3 years in consultancy activities for AstraZeneca, GlaxoSmithKline, Neolab, and Nycomed. He has spoken at meetings sponsored by GlaxoSmithKline and Nycomed.

Role of sponsors: This study was funded by Nycomed. Analyses were performed by both Nycomed and an independent statistician (J. Vonk). Medicus International provided editorial assistance with the manuscript. Editorial support was funded by Nycomed.

Other contributions: This multicenter study was performed at a number of different institutes (see e-Appendix 1 for a list of participating investigators). We thank Dr J. Vonk for analyzing the data set as an independent statistician.

Additional information: The e-Appendix can be found in the Online Supplement at http://chestjournal.chestpubs.org/content/139/2/311/suppl/DC1.

AE

adverse event

AQLQ(S)

standardized version of the Asthma Quality of Life Questionnaire

CIC160

ciclesonide 160 μg once daily

FP200/S100

fluticasone propionate/salmeterol 100/0 μg bid

ICS

inhaled corticosteroid

ITT

intention-to-treat

LABA

long-acting β2-agonist

OPTIMA

Optimal Treatment of Mild Asthma

PEF

peak expiratory flow

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Hansel TT, Benezet O, Kafé H, et al. A multinational, 12-week, randomized study comparing the efficacy and tolerability of ciclesonide and budesonide in patients with asthma. Clin Ther. 2006;286:906-920. [CrossRef] [PubMed]
 
Niphadkar P, Jagannath K, Joshi JM, et al. Comparison of the efficacy of ciclesonide 160 μg QD and budesonide 200 μg BID in adults with persistent asthma: a phase III, randomized, double-dummy, open-label study. Clin Ther. 2005;2711:1752-1763. [CrossRef] [PubMed]
 
Buhl R, Vinkler I, Magyar P, et al. Comparable efficacy of ciclesonide once daily versus fluticasone propionate twice daily in asthma. Pulm Pharmacol Ther. 2006;196:404-412. [CrossRef] [PubMed]
 
Subbarao P, Duong M, Adelroth E, et al. Effect of ciclesonide dose and duration of therapy on exercise-induced bronchoconstriction in patients with asthma. J Allergy Clin Immunol. 2006;1175:1008-1013. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. Diagram of patient disposition. CIC160 = ciclesonide 160 μg once daily; FP200/S100 = fluticasone propionate/salmeterol 100/50 μg bid.Grahic Jump Location
Figure Jump LinkFigure 2. Kaplan-Meier plot showing time to first exacerbation (intention-to-treat analysis). See Figure 1 legend for expansion of abbreviations.Grahic Jump Location
Figure Jump LinkFigure 3. Percentage of patients with asthma symptom-free days, rescue medication-free days, and asthma control days at the end of the treatment period. Asthma symptom-free days and asthma control days are the last 28 days before the last visit; rescue medication-free days are the week before the last visit. *P < .01, one-sided, vs placebo. †P < .001, one-sided, vs placebo. See Figure 1 legend for expansion of abbreviations.Grahic Jump Location
Figure Jump LinkFigure 4. A, Least squares mean change in overall standardized asthma quality of life from baseline to study end (intention-to-treat population). B, Percentage of patients who showed an improvement in AQLQ(S) score ≥ 0.5 (intention-to-treat population). Least squares mean at baseline was 5.82 for all treatment groups. *P ≤ .0017, one-sided, vs placebo. AQLQ(S) = standardized version of the Asthma Quality of Life Questionnaire. See Figure 1 legend for expansion of other abbreviations.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Patient Baseline and Demographic Characteristics (Intention-to-Treat Population)

Data are presented as mean ± SD, unless otherwise indicated. AQLQ(S) = standardized version of the Asthma Quality of Life Questionnaire; CIC160 = ciclesonide 160 μg once daily; FP200/S100 = fluticasone propionate/salmeterol 100/50 μg bid.

a 

Data shown are from 14 d before baseline.

Table Graphic Jump Location
Table 2 —Between- and Within-Treatment Differences for Coprimary and Secondary Variables at End of Study (Intention-to-Treat Population)

N/A = not applicable; PEF = peak expiratory flow. See Table 1 legend for expansion of other abbreviations.

a 

Least squares analysis.

Table Graphic Jump Location
Table 3 —Frequently Reported Adverse Events in the Safety Population (≥ 5% of Patients in Any Treatment Group)

Data are presented as No. (%). See Table 1 legend for expansion of abbreviations.

References

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Niphadkar P, Jagannath K, Joshi JM, et al. Comparison of the efficacy of ciclesonide 160 μg QD and budesonide 200 μg BID in adults with persistent asthma: a phase III, randomized, double-dummy, open-label study. Clin Ther. 2005;2711:1752-1763. [CrossRef] [PubMed]
 
Buhl R, Vinkler I, Magyar P, et al. Comparable efficacy of ciclesonide once daily versus fluticasone propionate twice daily in asthma. Pulm Pharmacol Ther. 2006;196:404-412. [CrossRef] [PubMed]
 
Subbarao P, Duong M, Adelroth E, et al. Effect of ciclesonide dose and duration of therapy on exercise-induced bronchoconstriction in patients with asthma. J Allergy Clin Immunol. 2006;1175:1008-1013. [CrossRef] [PubMed]
 
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