Effects of ciclesonide and fluticasone on cortisol secretion in patients with persistent asthma

Derom, Eric; Louis, Renaud; Tiesler, Christine; Engelstätter, Renate; Kaufman, Jean; Joos, Guy

doi:10.1183/09031936.00079908

Cited by 19 publications

(20 citation statements)

References 49 publications

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“…12 In an earlier phase II study, FP 500 mg twice daily had a similar efficacy to FF 200 mg once daily (vs placebo) in patients with persistent moderate-to-severe asthma. 7 However, FP 500 mg twice daily is associated with more steroid-associated AEs than lower FP doses [13][14][15] and this dose of FP was therefore selected in our study as a benchmark to which FF/VI safety data could be compared. The patient population contained a wide age range (12-73 years) in order to adequately assess the safety and tolerability of FF/VI in adolescent and adult patients with asthma.…”

Section: Discussionmentioning

confidence: 99%

Safety and tolerability of the novel inhaled corticosteroid fluticasone furoate in combination with the β₂agonist vilanterol administered once daily for 52 weeks in patients ≥12 years old with asthma: a randomised trial

Busse

O'Byrne

Bleecker

et al. 2013

Thorax

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BackgroundThe inhaled corticosteroid fluticasone furoate (FF) in combination with the long-acting β2 agonist vilanterol (VI) is in development for asthma and chronic obstructive pulmonary disease.ObjectiveTo assess the safety and tolerability of FF/VI over 52 weeks in patients with asthma.MethodsPatients (aged ≥12 years; on inhaled corticosteroid) were randomised (2:2:1) to FF/VI 100/25 µg or FF/VI 200/25 µg once daily in the evening, or fluticasone propionate (FP) 500 µg twice daily. Safety evaluations included adverse events (AEs), non-fasting glucose, potassium, 24-h urinary cortisol excretion, ophthalmic assessments, heart rate and pulse rate.ResultsOn-treatment AEs were similar across groups (FF/VI 66–69%; 73% FP). Oral candidiasis/oropharyngeal candidiasis was more common with FF/VI (6–7%) than FP (3%). Twelve serious AEs were reported; one (worsening hepatitis B on FP) was considered drug related. Statistically significant cortisol suppression was seen with FP compared with both FF/VI groups at Weeks 12 and 28 (ratios [95% CI] to FP ranged from 1.43 [1.11 to 1.84] to 1.67 [1.34 to 2.08]; p≤0.006), but not at Week 52 (ratios to FP were 1.05 [0.83 to 1.33] for FF/VI 100/25 µg and 1.09 [0.87 to 1.38] for FF/VI 200/25 µg). No clinically important changes in non-fasting glucose, potassium, QT interval corrected using Fridericia's formula (QTc[F]) or ophthalmic assessments were reported. Pulse rate (10 min post dose [Tmax], Week 52) was significantly increased with FF/VI versus FP (3.4 bpm, 95% CI 1.3 to 5.6; p=0.002 [FF/VI 100/25 µg]; 3.4 bpm, 95% CI 1.2 to 5.6; p=0.003 [FF/VI 200/25 µg]). Mean heart rate (24-h Holter monitoring) decreased from screening values in all groups (0.2–1.1 bpm FF/VI vs 5 bpm FP; Week 52).ConclusionsFF/VI (100/25 µg or 200/25 µg) administered once daily over 52 weeks was well tolerated by patients aged ≥12 years with asthma. The overall safety profile of FF/VI did not reveal any findings of significant clinical concern.ClinicalTrials.govNCT01018186

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Section: Discussionmentioning

confidence: 99%

Safety and tolerability of the novel inhaled corticosteroid fluticasone furoate in combination with the β₂agonist vilanterol administered once daily for 52 weeks in patients ≥12 years old with asthma: a randomised trial

Busse

O'Byrne

Bleecker

et al. 2013

Thorax

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“…Unlike other ICS medications, ciclesonide appears to have little or no suppressive effects on the HPA axis [80]. Clinical studies of ciclesonide administered at doses up to 640 μg/day have failed to show any significant effects of this ICS on serum or 24-hour urinary cortisol levels [81-83].…”

Section: Effects Of Ics Therapy On Adrenal Suppression (As): Review Omentioning

confidence: 99%

“…In patients on supraphysiological doses of oral corticosteroids for more than 2 consecutive weeks or those who have required more than 3 weeks of oral steroids over the course of 6 months, tapering of steroids should be considered to allow for adrenal recovery. In patients with proven AS, consideration should also be given to the use of ciclesonide, which has been shown to have little or no suppressive effects on the HPA axis [80]. …”

Section: Recommendations For the Prevention Screening And Managementmentioning

confidence: 99%

Adrenal suppression: A practical guide to the screening and management of this under-recognized complication of inhaled corticosteroid therapy

Ahmet

Kim

Spier

2011

All Asth Clin Immun

128

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Inhaled corticosteroids (ICSs) are the most effective anti-inflammatory agents available for the treatment of asthma and represent the mainstay of therapy for most patients with the disease. Although these medications are considered safe at low-to-moderate doses, safety concerns with prolonged use of high ICS doses remain; among these concerns is the risk of adrenal suppression (AS). AS is a condition characterized by the inability to produce adequate amounts of the glucocorticoid, cortisol, which is critical during periods of physiological stress. It is a proven, yet under-recognized, complication of most forms of glucocorticoid therapy that can persist for up to 1 year after cessation of corticosteroid treatment. If left unnoticed, AS can lead to significant morbidity and even mortality. More than 60 recent cases of AS have been described in the literature and almost all cases have involved children being treated with ≥500 μg/day of fluticasone.The risk for AS can be minimized through increased awareness and early recognition of at-risk patients, regular patient follow-up to ensure that the lowest effective ICS doses are being utilized to control asthma symptoms, and by choosing an ICS medication with minimal adrenal effects. Screening for AS should be considered in any child with symptoms of AS, children using high ICS doses, or those with a history of prolonged oral corticosteroid use. Cases of AS should be managed in consultation with a pediatric endocrinologist whenever possible. In patients with proven AS, stress steroid dosing during times of illness or surgery is needed to simulate the protective endogenous elevations in cortisol levels that occur with physiological stress.This article provides an overview of current literature on AS as well as practical recommendations for the prevention, screening and management of this serious complication of ICS therapy.

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“…The pharmacokinetic profiles of serum des-CIC concentrations measured over time indicated that drug inhalation by patients (of whom, the majority were ex-or current smokers) was adequate; the AUC of des-CIC in this study was 6.68 mg?h?L [16,17]. The pharmacokinetic and pharmacodynamic properties of inhaled ciclesonide have been described in recent publications [22][23][24].…”

Section: Discussionmentioning

confidence: 97%

Deposition and metabolism of inhaled ciclesonide in the human lung

Nave¹,

Watz²,

Hoffmann³

et al. 2010

European Respiratory Journal

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Ciclesonide is an inhaled corticosteroid, administered as a prodrug via a metereddose inhaler. Following deposition in the lung, ciclesonide is hydrolysed by esterases to form the pharmacologically active metabolite desisobutyryl-ciclesonide (des-CIC). Formation of des-CIC, as well as reversible esterification of des-CIC with fatty acids, has been demonstrated in vitro. The aim of this study was to investigate the in vivo metabolism of ciclesonide in the human lung.This single-dose, open-label, nonrandomised study was performed in 20 patients undergoing planned lung surgery for treatment of malignant pulmonary lesions. Patients inhaled a single dose of 1,280 mg ciclesonide at various time-points between 2 and 24 h prior to lung tissue resection. The concentration of ciclesonide, des-CIC and fatty acid conjugates of des-CIC in tissue samples was determined. Serum samples for pharmacokinetic analysis were taken at several time-points after inhalation.The pharmacokinetics in serum indicated that the inhalation by the patients was adequate. Metabolites (des-CIC, des-CIC oleate and des-CIC palmitate) were detected in the resected central and peripheral lung tissues. A substantial portion of ciclesonide was already activated to des-CIC at the first time-point of tissue analysis.Activation of ciclesonide and formation of des-CIC fatty acid conjugates was confirmed in vivo in the human lung.

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Effects of ciclesonide and fluticasone on cortisol secretion in patients with persistent asthma

Cited by 19 publications

References 49 publications

Safety and tolerability of the novel inhaled corticosteroid fluticasone furoate in combination with the β₂agonist vilanterol administered once daily for 52 weeks in patients ≥12 years old with asthma: a randomised trial

Safety and tolerability of the novel inhaled corticosteroid fluticasone furoate in combination with the β₂agonist vilanterol administered once daily for 52 weeks in patients ≥12 years old with asthma: a randomised trial

Adrenal suppression: A practical guide to the screening and management of this under-recognized complication of inhaled corticosteroid therapy

Deposition and metabolism of inhaled ciclesonide in the human lung

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Effects of ciclesonide and fluticasone on cortisol secretion in patients with persistent asthma

Cited by 19 publications

References 49 publications

Safety and tolerability of the novel inhaled corticosteroid fluticasone furoate in combination with the β2agonist vilanterol administered once daily for 52 weeks in patients ≥12 years old with asthma: a randomised trial

Safety and tolerability of the novel inhaled corticosteroid fluticasone furoate in combination with the β2agonist vilanterol administered once daily for 52 weeks in patients ≥12 years old with asthma: a randomised trial

Adrenal suppression: A practical guide to the screening and management of this under-recognized complication of inhaled corticosteroid therapy

Deposition and metabolism of inhaled ciclesonide in the human lung

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Product

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About

Safety and tolerability of the novel inhaled corticosteroid fluticasone furoate in combination with the β₂agonist vilanterol administered once daily for 52 weeks in patients ≥12 years old with asthma: a randomised trial

Safety and tolerability of the novel inhaled corticosteroid fluticasone furoate in combination with the β₂agonist vilanterol administered once daily for 52 weeks in patients ≥12 years old with asthma: a randomised trial