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Ciclesonide Impacts Clinicopathological Features of Pediatric Eosinophilic Esophagitis


Doctor inspects young patient's stomach

Key takeaways

  • Swallowed ciclesonide (CIC) is another option for treating pediatric patients with EoE.

  • CIC use reduced EoE symptoms, improved esophageal endoscopic appearance, and decreased epithelial inflammation without significant side effects.

  • CIC effectively treats EoE topically with low systemic steroid bioavailability, potentially reducing adrenal suppression risk.

Research background: adrenal insufficiency a possibility with swallowed topical corticosteroids

Eosinophilic esophagitis (EoE) is a chronic disease of the esophagus caused most often by food allergens. In patients with EoE, an immunologic reaction to a food allergen causes eosinophils to build up in the lining of the esophagus resulting in inflammation, abdominal pain, reflux and swallowing or feeding problems.

Treatment for EoE includes:

  • Dietary elimination therapy
  • Proton pump inhibitors
  • Swallowed topical steroids (STS) – most effective medical treatment although no formulations yet approved by Food and Drug Administration
  • Esophageal dilation

Swallowed fluticasone propionate and oral viscous budesonide are the most commonly used STS formulations. Risks of long-standing use of STS include the infrequent occurrence of adrenal insufficiency.

The topical corticosteroid CIC is used for asthma and allergic rhinitis treatment and delivers potent STS activity with less systemic bioavailability than existing topical steroid formulations.

Previous research from the Digestive Health Institute found that similar to airway epithelium, esophageal epithelium expresses carboxylesterases 1 and 2, enzymes required for conversion of CIC to the active form, des-CIC1. Both CIC and des-CIC form reversible lipid conjugates that act as a drug depot2, which has been theorized to increase the duration of action in the treatment of asthma.

While CIC local activity is clinically equivalent to fluticasone propionate, systemic bioavailability is approximately less than 1%. A German asthma study found a low percentage of CIC deposited in the oropharynx was converted to active des-CIC3. A lower systemic bioavailability could mean there is less suppression of the hypothalamic- pituitary-adrenal axis. Additionally, with less active drug in the oropharynx, CIC may lead to fewer cases of oral candidiasis compared to patients treated with fluticasone propionate.

Mason Nistel, MD, and Calies Menard-Katcher, MD, researchers in the Digestive Health Institute at Children’s Hospital Colorado, hypothesized CIC may be an option to consider in patients with EoE who:

  • Require multiple corticosteroid medications for concomitant atopic disease(s)
  • Require high STS doses for EoE disease control
  • Develop adverse drug reactions on current treatment regimen

Study authors examined whether CIC can effectively induce or maintain histologic remission and clinical improvement in patients with EoE. They also sought to determine the drug’s potential for adverse effects.

Research methods: study of EoE patients treated with CIC at Children’s Colorado

Details of the retrospective observational cohort study


A diagnosis of EoE was based on clinicopathologic diagnostic criteria requiring both esophageal symptoms and esophageal biopsies with more than 15 eosinophils/high-powered field.

Research results: CIC use reduced symptoms in EoE patients without significant side effects

Patient population



  • 62 of 81 patients were previously treated with another STS for EoE.
  • 19 patients were STS naïve when starting CIC.
  • 33 patients were treated with an additional topical steroid (inhaled, intranasal, or dermatologic) for a concomitant atopic disease.
  • 5 patients were treated with 2 additional steroid formulations.

Reasons for changing to CIC

  • Lack of adequate response to other therapies (most common)
  • Behavioral issues
  • Insurance issues
  • Risk of adrenal insufficiency
  • Recurrent Candida infection
  • Confirmed adrenal insufficiency
  • Other issues: concern for side effects, problems with other STS, or not stated

CIC treatment doses were started at either 320 µg/day (80 µg, 2 puffs swallowed twice daily) in children under 12 years, or 640 µg/day (160 µg, 2 puffs swallowed twice daily) in children older than 12 years.



Mucosal appearance

Endoscopies were performed before initiation of CIC and after an average of 11.5 months in 79 patients (2 patients were missing pre- and post-CIC endoscopic data).

After treatment:

  • Endoscopic reference score, a validated endoscopic score of EoE disease activity, significantly decreased (improved).
  • Individual components of this score reflective of inflammation decreased significantly; these included edema, exudates and furrows.
  • Individual components of this score reflective of chronic changes (esophageal rings and strictures) did not change significantly.

Histological response

CIC treatment significantly decreased esophageal mucosal eosinophilia.

Histologic remission was defined as <15 eosinophils/high-powered field, with these results:

  • 17.3% were in histologic remission before starting CIC (due to previous treatments).
  • 53% met criteria for histologic remission after CIC treatment (p < 0.001).
  • Response varied among age groups:
    • 2- to 11-year-olds with 62.5% histologic remission
    • 12- to 23-year-olds with only 32% in histologic remission
  • In steroid naïve subjects treated >16 weeks histologic remission occurred in 67%.

Adverse reactions


Cortisol level

  • Cortisol was measured and abnormal in 10 of 31 patients during the study period.
  • 6 of 10 had an abnormal ACTH stimulation test.
  • No other non-iatrogenic etiologies were found.

Six patients diagnosed with adrenal insufficiency (AI) during the study period.

  • 4 of 6 were on concomitant topical corticosteroids.
  • 5 of 6 had been transitioned to CIC due AI diagnosis.
  • 1 of 6 redeveloped AI on CIC after a past diagnosis and recovery of iatrogenic AI (due to inhaled steroids prescribed for asthma).
  • 3 of 6 experienced normalization of adrenal function while continuing CIC.
  • 3 of 6 had ongoing AI and required ongoing stress dose steroid precautions without normalization of adrenal function during the study period.

None of the 81 patients exhibited clinical features of AI, and no one diagnosed with AI had adrenal crises or fractures during the study period.

Research discussion and conclusion: CIC found to be effective for EoE patients with limited systemic exposure

In this report of 10 years of CIC treatment for treatment of pediatric EoE, results demonstrate a reduction of symptoms, mucosal abnormalities and esophageal eosinophilia with few associated side effects, thus supporting its use for the treatment of patients with EoE.

Key findings from the study

  • CIC reduced symptoms and improved endoscopic and histologic features of EoE.
  • Most symptomatic patients experienced symptom reduction (75%), specifically with decreases in dysphagia and abdominal pain.
  • CIC led to significant improvements in esophageal edema, exudates and furrows (thought to reflect the inflammatory signs of EoE).
  • Overall, 53% of subjects achieved or maintained histologic remission on CIC.
    • 56% of subjects transitioned to CIC due to lack of adequate response to other therapies, which may suggest a treatment-resistant population.
    • 29% of subjects with persistent inflammation on first-line STS formulations achieved histologic remission on CIC.
  • Histologic remission of <15 eosinophils/high-powered field was highest in:
    •  STS naïve patients at 60%
    • STS naïve patients on CIC for >16 weeks at 67%
  • Efficacy was lower in patients 12-23 years old, which was possibly due to lower adherence or other confounders.
  • CIC did not lead to development of symptomatic or worsening adrenal function in the limited number of patients monitored for AI.
  • AI rate is lower with CIC than other STS formulations possibly due to limited systemic bioavailability.

Study authors state the potential development of AI in patients with EoE is an important consideration when treating EoE patients with STS. Their previous study found most patients with EoE treated with STS who developed AI were treated with more than one topical steroid. They recommend monitoring the dose, potency, and number of topical steroid treatments for patients with EoE. CIC can be considered an alternative therapy in patients with known AI or at risk of developing AI.

  1. Schroeder S, Fleischer DM, Masterson JC, Gelfand E, Furuta GT, Atkins D. Successful treatment of eosinophilic esophagitis with ciclesonide. J Allergy Clin Immunol. 2012;129(5):1419-21.
  2. Nave R, Meyer W, Fuhst R, Zech K. Formation of fatty acid conjugates of ciclesonide active metabolite in the rat lung after 4-week inhalation of ciclesonide. Pulmonary Pharmacology & Therapeutics. 2005;18(6):390-6.
  3. Richter K, Kanniess F, Biberger C, Nave R, Magnussen H. Comparison of the oropharyngeal deposition of inhaled ciclesonide and fluticasone propionate in patients with asthma. J Clin Pharmacol. 2005;45(2):146-52.