Chest
Volume 129, Issue 5, May 2006, Pages 1176-1187
Journal home page for Chest

Original Research: Asthma
Ciclesonide Reduces the Need for Oral Steroid Use in Adult Patients With Severe, Persistent Asthma

https://doi.org/10.1378/chest.129.5.1176Get rights and content

Study objectives

Oral corticosteroids (OCS) may be associated with systemic adverse events (AEs), which can be reduced by replacing OCS with inhaled corticosteroids (ICS). The potential of ciclesonide, a novel ICS, to reduce OCS use in patients with severe, persistent asthma was evaluated in this study.

Design

A phase III, 12-week, international, multicenter, double-blind, placebo-controlled, parallel-group study.

Patients

Adult and adolescent patients (≥ 12 years old; n = 141) with severe, persistent, oral steroid (prednisone)-dependent asthma.

Interventions

Patients were randomized to receive ciclesonide (640 μg/d or 1,280 μg/d [ex-actuator]) bid or placebo for 12 weeks. Weekly evaluations determined eligibility for prednisone dose reduction based on predetermined criteria.

Measurements and results

The prednisone dose was significantly reduced by 47% and 63% in the groups receiving ciclesonide, 640 μg/d, and ciclesonide, 1,280 μg/d, respectively, vs an increase of 4% in the placebo group (both p ≤ 0.0003) at week 12. By week 12, prednisone was discontinued by approximately 30% of patients in the ciclesonide-treated groups, vs 11% of patients in the placebo group (both p ≤ 0.04). FEV1 improved significantly at week 12 in the ciclesonide treatment groups vs placebo (p < 0.03). The occurrence of local and systemic AEs was comparable between all treatment groups.

Conclusion

Study results suggest that ciclesonide significantly reduces the need for OCS in patients with severe, persistent asthma, while maintaining asthma control.

Section snippets

Methods and Materials

Male and female patients aged ≥ 12 years with OCS-dependent, severe, persistent asthma (according to the Global Initiative for Asthma guidelines35) diagnosed at least 12 months prior to screening were enrolled in a 12-week, international, randomized, double-blind, placebo-controlled, parallel-group study. Patients were required to have received oral prednisone daily or on alternate days for at least 5 of the previous 6 months (5 to 30 mg/d and/or 10 to 60 mg every other day) and to have

Patient Characteristics

The trial was conducted between July 2001 and March 2003. Overall, 241 patients were screened, and 141 patients (80 in the United States and 61 in South Africa) were randomized to receive treatment at 60 sites within these countries (CIC640, n = 47; CIC1280, n = 49; placebo, n = 45). Patient disposition throughout the clinical trial is shown in Figure 1. The ITT population consisted of 140 patients; 1 patient in the CIC1280 group was excluded due to not having postbaseline measurements. All 141

Discussion

This study was designed to assess the OCS-sparing potential of ciclesonide in adult and adolescent patients with OCS-dependent, severe, persistent asthma. The results suggested that the substitution of twice-daily inhaled ciclesonide for high doses of other forms of ICS significantly reduced the dose of prednisone required by these patients. Although no significant dose-response effect was noted between the 640 μg/d and 1,280 μg/d dosages, the higher dose demonstrated a greater numeric trend

Conclusion

In conclusion, the results of this study suggest that twice-daily treatment with inhaled ciclesonide (640 μg/d or 1,280 μg/d) is a well-tolerated method for reducing (and potentially discontinuing) OCS use in patients with severe, persistent asthma, thus minimizing the risk of the AEs associated with OCS use.

ACKNOWLEDGMENT

We thank the following investigators for their participation in the study: Abdool-Gaffar, Mohamed; Abdullah, Ismail; Albery, Richard; Algatt-Bergstrom, Pamela; Bailey, William; Baz, Malik; Bernstein, David; Busse, William; Butterfield, Joseph; Caldwell, Jacques; Calhoun, William; Chipps, Bradley; Colice, Gene; Condemi, John; Conway, Michael; Cook, David; Craig, Timothy; Daffern, Pamela; D'Alonzo, Gilbert; Duvenhage, Cornelia; Fidelholtz, James; Fink, Jordan; Fino, Gregory; Foden, Alwyn; Fox,

References (42)

  • RingdalN et al.

    Comparable effects of inhaled fluticasone propionate and budesonide on the HPA-axis in adult asthmatic patients

    Respir Med

    (2000)
  • FishJE et al.

    Inhaled mometasone furoate reduces oral prednisone requirements while improving respiratory function and health-related quality of life in patients with severe persistent asthma

    J Allergy Clin Immunol

    (2000)
  • BrownPH et al.

    High dose inhaled steroid therapy and the cortisol stress response to acute severe asthma

    Respir Med

    (1992)
  • LipworthB et al.

    Effect of ciclesonide and fluticasone on hypothalamic-pituitary-adrenal axis function in adults with mild-to-moderate persistent asthma

    Ann Allergy Asthma Immunol

    (2005)
  • BelvisiMG et al.

    New glucocorticosteroids with an improved therapeutic ratio?

    Pulm Pharmacol Ther

    (2001)
  • National Asthma Education and Prevention Program: expert panel report; guidelines for the diagnosis and management of asthma, update on selected topics-2002

    J Allergy Clin Immunol

    (2002)
  • AdachiJD

    Corticosteroid-induced osteoporosis

    Int J Fertil Womens Med

    (2001)
  • LacroniqueJ et al.

    High-dose beclomethasone: oral steroid-sparing effect in severe asthmatic patients

    Eur Respir J

    (1991)
  • TanWC et al.

    The efficacy of high dose inhaled budesonide in replacing oral corticosteroid in Asian patients with chronic asthma

    Singapore Med J

    (1990)
  • Mc MurtrySA et al.

    High dose inhaled fluticasone propionate improves FEV1and results in reduction of oral glucocorticoid dose in glucocorticoid-dependent children with severe asthma

    Allergy Asthma Proc

    (2001)
  • WenzelSE et al.

    Improvement in health care utilization and pulmonary function with fluticasone propionate in patients with steroid-dependent asthma at a national asthma referral center

    J Asthma

    (2001)
  • Cited by (43)

    • Improving asthma outcomes: Clinicians’ perspectives on peripheral airways

      2024, Journal of Allergy and Clinical Immunology: Global
    • Inhaled ciclesonide for outpatient treatment of COVID-19 in adults at risk of adverse outcomes: a randomised controlled trial (COVERAGE)

      2022, Clinical Microbiology and Infection
      Citation Excerpt :

      One of the treatments studied was inhaled ciclesonide. Ciclesonide has a favourable safety profile and anti-inflammatory properties for the respiratory tract [10]. The onset of action is faster with ciclesonide than with budesonide for improving lung function in asthmatic patients [11].

    • Repurposing drugs as inhaled therapies in asthma

      2018, Advanced Drug Delivery Reviews
      Citation Excerpt :

      Ciclesonide by contrast is a pro-drug that becomes active on reaching the site of action in the lung [91, 92]. Ciclesonide 640 μg and 1280 μg twice daily for 12 weeks reduced the need for oral cortico-steroids in those with severe and persistent asthma with discontinuation of prednisone at 12 weeks in 30% of patients on ciclesonide versus 11% on placebo [93]. Ciclesonide 320 μg four times daily was shown to have similar efficacy to budesonide 800 μg four times daily in adolescents with severe asthma [94].

    • Asthma outcomes: Exacerbations

      2012, Journal of Allergy and Clinical Immunology
    View all citing articles on Scopus

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

    This study was funded by sanofi-aventis U.S. Inc., a member of the sanofi-aventis Group, and ALTANA Pharma AG.

    Dr. Bateman has served as a consultant and is a member of an advisory board for Aventis Pharma. Dr. Karpel is a member of an advisory board for ALTANA and Schering-Plough; is on the Speaker's Bureau for Boehringer-Ingelheim, Genentech, Glaxo, Novartis, Pfizer, and Schering-Plough; and has received grants from AstraZeneca, ALTANA, Boehringer-Ingelheim, Dey, and Genentech. Dr. Casale has served as a consultant for Allux, Aperon, Aventis, Corixa, Genentech, Merck, Novartis, and Sugitomo; is a member of a Data Monitoring Board for Hoffman-LaRoche; is on a Speaker's Bureau and has given talks sponsored by Aventis, Genentech, Novartis, and Merck; and is an investigator for contract research performed through Creighton University for Capnia, Corixa, Dynavax, IDEC, MediciNova, Merck, NIAID/ITN, Novartis, Ono, and Pfizer. Dr. Wenzel has received grants from and has served as a consultant and is a member of an advisory board for ALTANA and sanofi-aventis. Dr. Banerji is an employee of sanofi-aventis and holds stock options in the company.

    This was an international study conducted in the United States and South Africa.

    Data from this study have been previously reported in the form of an abstract to the American Thoracic Society International Congress, San Diego, CA 2005.

    View full text