Ciclesonide: An Expert Interview With David I. Bernstein, MD

October 13, 2005

Editor's Note:
Ciclesonide is a corticosteroid currently approved in Europe for the treatment of inflammation that is the critical source of asthma symptoms. Data were recently presented at US conferences discussing this new medication. David I. Bernstein, MD, Professor of Medicine in the Division of Immunology and Allergy at the University of Cincinnati College of Medicine, Cincinnati, Ohio, has conducted research on ciclesonide and was interviewed by Melinda Tanzola, PhD, for Medscape, and to discuss why this corticosteroid is different.

Dr. Tanzola: What is ciclesonide and what are its intended clinical indications?

Dr. Bernstein: Ciclesonide is a new inhaled corticosteroid that will be indicated for the treatment of asthma in adults and, hopefully, in children.

Dr. Tanzola: How does ciclesonide differ from other inhaled corticosteroids?

Dr. Bernstein: Ciclesonide, like all corticosteroids, is anti-inflammatory, so it controls the inflammation that is the critical source of asthma symptoms. What makes it unique is that it has a much better safety profile than other available inhaled corticosteroids. This is likely due to the different deposition characteristics of the drug. With its hydrofluoroalkane vehicle and valve on the metered dose inhaler, most of the ciclesonide particles are delivered in a much smaller size. This allows the particles to bypass the larynx and nasopharyngeal area and target to the lung. With less corticosteroid being trapped or deposited in the oral cavity, candidiasis is less likely to colonize.

Dr. Tanzola: How has ciclesonide performed in clinical trials, in terms of its ability to restore lung function and improve quality of life for patients with asthma?

Dr. Bernstein: This drug has been shown to be clinically significantly effective in all types of patients, including those characterized as having mild-to-moderate asthma as well as those with severe asthma. In a study presented at the recent American Thoracic Society (ATS) meeting, ciclesonide was shown to significantly improve lung function, particularly in the morning.[1] Many patients treated with ciclesonide reported doing well, whereas many placebo-treated patients had to withdraw.

A study presented at the recent American Academy of Asthma, Allergy, and Immunology (AAAAI) meeting demonstrated the efficacy of ciclesonide in patients with severe, persistent asthma.[2] It was a double-blinded, placebo-controlled study evaluating patients exhibiting only 40% to 65% of predicted forced expiratory volume in 1 second (FEV1). Patients were randomized to high-dose ciclesonide (320 or 640 mcg/day), fluticasone (880 mcg/day), or placebo. Ciclesonide gave significant improvement over placebo at both doses tested. By evaluating patients with the most severe disease, this study really tested the ability of the drug to be effective.

Dr. Tanzola: How do the dosing requirements compare with other inhaled corticosteroids?

Dr. Bernstein: Ciclesonide is unique in that it offers once-daily dosing, which has not been standard for inhaled corticosteroids. This regimen offers an advantage in terms of patient compliance and adherence to physician recommendations. Mometasone is another new inhaled corticosteroid that will also be available with once-daily dosing.

Dr. Tanzola: What is the safety profile of ciclesonide?

Dr. Bernstein: Clinical trials seem to indicate a much lower incidence of local adverse effects in the mouth and throat, primarily in terms of local colonization with candidiasis, which is a known side effect of inhaled steroids. The local deposition of ciclesonide in the lung likely prevents candidiasis colonization. In the ATS study, 11% of patients treated with fluticasone developed thrush, vs 0% at equivalent doses of ciclesonide. There is a clear advantage for the patients who have to deal with these symptoms on a day-to-day basis.

Systemic effects are a concern when using inhaled corticosteroids. Certain agents reduce the growth rate of preadolescent children, particularly boys, to a small extent. Ciclesonide appears to be safe in terms of its systemic effects on the body. It does not appear at this point to suppress cortisol secretion or to cause suppression of the HPA axis, which would indicate that in all likelihood it will cause fewer problems with growth in children.[2] However, we are still waiting for the data from growth studies to come out.

Dr. Tanzola: Ciclesonide is currently available in Europe but has not yet been approved by the US Food and Drug Administration. At what stage in the approval process is ciclesonide?

Dr. Bernstein: Safety studies are still being completed. One current study is investigating ocular changes. That data and the growth data should be forthcoming. I think these studies will probably show the drug is safe, but the studies are not out yet. I would think by next year, when all the studies are completed, we would see the drug being released.

Dr. Tanzola: In summary, what would ciclesonide offer for physicians treating patients with asthma?

Dr. Bernstein: Ciclesonide appears as effective as other inhaled corticosteroids but has a much better safety profile. It would allow physicians to use this drug for treating asthma in any age category and with any severity with a large comfort zone that it does not have the potential to cause a lot of side effects. Physicians could feel comfortable using high doses if needed, without having problems with thrush that limit their ability to increase the dose.

Interviewer's note:

Many abstracts from the 2005 AAAAI and ATS meetings investigated the efficacy and safety of ciclesonide in a variety of patient populations. In our interview, Dr. Bernstein highlighted 2 abstracts. The first was a compilation of 2 identical, randomized, placebo-controlled studies that enrolled a total of 1015 patients with mild-to-moderate asthma, defined as having an FEV1 60% to 85% of predicted value.[1] Patients (all at least 12 years of age) received 80, 160, or 320 mcg ciclesonide or placebo daily for 12 weeks. Ciclesonide was significantly more effective than placebo at all doses tested. From baseline to week 12, the mean morning PEF change was 10.93 L/minute with 80 mcg ciclesonide, 21.06 L/minute with 160 mcg, 17.22 L/minute with 320 mcg (P = .0008, < .0001, and < .0001, respectively, vs placebo), and -1.70 L/minute with placebo. Significantly fewer ciclesonide-treated patients discontinued treatment due to failure (9.7%, 7.6%, 6.7%, and 24.9%, respectively; P < .0001 for all ciclesonide doses vs placebo). The treatment was well tolerated, with adverse effects comparable to placebo.

The second study, a multicenter, double-blind trial, enrolled 531 patients at least 12 years of age with severe asthma, defined as having 60% to 85% of predicted FEV1.[2] Patients received twice-daily administration of ciclesonide (160 or 320 mcg), 440 mcg fluticasone propionate (FP), or placebo for 12 weeks. To maintain blinding, the FP dose was increased by 37%. Both ciclesonide and FP were effective and provided significant improvements in FEV1 over placebo (0.11 L with 320 mcg ciclesonide, 0.18 L with 640 mcg ciclesonide, and 0.24 L with 880 mcg FP). With all active drugs, patients reported significantly improved 24-hour asthma symptoms and less daily albuterol use compared with patients receiving placebo. Treatments were generally well tolerated, and the percentage of patients reporting at least 1 treatment-related adverse event was similar between treatment arms. However, more patients treated with FP developed oral candidiasis (11.6% vs 1.6% with 320 mcg ciclesonide, 0% with 640 mcg ciclesonide, and 2.2% with placebo). The development of trace cataracts was noted in 13 patients who had normal lenses at baseline, although the clinical significance of this finding is unclear. HPA axis function appeared unaffected by any treatment as measured by changes in serum cortisol levels and 24-hour urinary free cortisol levels corrected for creatinine.

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