Inhaled Ciclesonide for the Treatment of Asthma (COPD) in Horses

In the introduction to this article, they state that inhaled ciclesonide has been found to be an effective treatment of equine asthma. Somehow, I missed that. Going to PubMed sure enough I found to recent studies supporting it’s use. Of note is that the ciclesonide seems to have less of the downsides of dex use. In particular, is the lack of suppression of immune function and cortisol. I do wonder what the cost is, dex remains cheap and effective.
DrO

The Effect of Inhaled Ciclesonide Treatment on Systemic Markers of Immune Function in Horses
Author links open overlay panelAllen E. Page a, Mackenzie Johnson a, Jordan L. Parker a, Olivia Jacob a, Melissa Swan b, Emma Adam a
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https://doi.org/10.1016/j.jevs.2023.104925
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Abstract
The use of dexamethasone to control equine asthma is a common and effective treatment. Although short-term systemic dexamethasone treatment has not been shown to induce systemic immunosuppression in the horse, the goal of this study was to determine whether inhaled ciclesonide, an FDA-approved drug for the treatment of equine asthma, exerts any systemic immunosuppressive effects when compared to dexamethasone-treated and untreated horses. Eighteen light, mixed breed horses, ranging in age from 3 to 8 years of age, were used for this study and randomly assigned to one of three treatment groups: (1) non-treated controls, (2) ciclesonide treatment, or (3) dexamethasone treatment. Blood was collected daily into RNA tubes for steady-state messenger RNA (mRNA) analysis, as well as at Days 0, 5, 10, and 15 of treatment for in vitro stimulation with Concanavalin A (ConA). Messenger RNA relative quantities were determined using RT-qPCR for select genes. Two-way, repeated measures analysis of variance was used to analyze qPCR data and results considered significant at P <0.05. There were significant decreases in the steady-state, whole-blood expression of granzyme B and interferon-γ due to dexamethasone treatment, when compared to the non-treated control group. Within ConA-stimulated samples, there remained a suppressive effect of dexamethasone treatment on granzyme B expression compared to non-treated control horses. Similar effects were not noted in the ciclesonide-treated horses. Significant effects of ciclesonide treatment on markers of immune function were not noted in this study, suggesting a low risk for immunosuppression with inhaled ciclesonide treatment.

Equine Vet J. 2021 Nov;53(6):1094-1104. doi: 10.1111/evj.13419. Epub 2021 Jan 28.
Inhaled ciclesonide is efficacious and well tolerated in the treatment of severe equine asthma in a large prospective European clinical trial
Robert Scott Pirie 1, Hanns-Walter Mueller 2, Odilo Engel 3, Balazs Albrecht 3, Marcella von Salis-Soglio 3
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PMID: 33403727 PMCID: PMC8518630 DOI: 10.1111/evj.13419
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Abstract
Background: Ciclesonide is a glucocorticoid prodrug, already registered for human use. Due to its mode of action and inhaled route of administration, it was considered an appropriate treatment option for horses with severe equine asthma. Although the efficacy of inhaled ciclesonide has been demonstrated in horses with asthma exacerbations under controlled mouldy hay challenge conditions, it has not yet been reported under field conditions.

Objectives: To assess the effectiveness and safety of inhaled ciclesonide for the treatment of severe equine asthma.

Study design: Prospective, multicentre, placebo-controlled, randomised, double-blinded study.

Methods: Two-hundred and twenty-four client-owned horses with severe equine asthma were randomised (1:1 ratio) to receive either ciclesonide inhalation (343 µg/actuation) solution or placebo (0 µg/actuation). Treatments (placebo or ciclesonide) were administered with a nonpressurised Soft Mist™ inhaler specifically developed for horses (Aservo® EquiHaler® ) at doses of 8 actuations twice daily for the first 5 days and 12 actuations once daily for the following 5 days. Primary outcome was a success/failure analysis with the a priori definition of treatment success as a 30% or greater reduction in weighted clinical score (WCS) between Day 0 and Day 10 (±1).

Results: The treatment success rate (as defined above) in ciclesonide-treated horses was 73.4% (80/109) after 10 (±1) days of treatment, being significantly higher than in the placebo group with 43.2% (48/111; P < 0.0001). Few systemic and local adverse events of ciclesonide were observed.Main limitations: The severity of clinical signs of severe equine asthma varies over time; despite the prohibition of environmental management changes during the study, a placebo effect was also identified. This potentially contributed, in part, to the clinical improvement observed in the ciclesonide-treated group.Conclusions: Ciclesonide inhalation solution administered by the Aservo® EquiHaler® effectively reduced severity of clinical signs in a majority of horses with severe equine asthma and was well tolerated.Keywords: ciclesonide; clinical trial; cough; equine asthma; heaves; horse; inhaled corticosteroids. © 2021 Boehringer Ingelheim Vetmedica GmbH. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd. Conflict of interest statement B. Albrecht, O. Engel and M. von Salis‐Soglio are employees of Boehringer Ingelheim Vetmedica GmbH, the marketing authorisation holder of Aservo® Equihaler® with ciclesonide as active ingredient. H.‐W. Mueller is an employee of Boehringer Ingelheim Pharma GmbH & Co KG. R.S. Pirie has acted as consultant to Boehringer Ingelheim Vetmedica GmbH. B. Albrecht is co‐inventor on a patent regarding the use of ciclesonide in horses.

Equine Vet J. 2019 Nov;51(6):779-786. doi: 10.1111/evj.13093. Epub 2019 Apr 5.
Effect of different doses of inhaled ciclesonide on lung function, clinical signs related to airflow limitation and serum cortisol levels in horses with experimentally induced mild to severe airway obstruction
J-P Lavoie 1, M Bullone 1, N Rodrigues 1, P Germim 1, B Albrecht 2, M von Salis-Soglio 2
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PMID: 30854685 PMCID: PMC7379559 DOI: 10.1111/evj.13093
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Abstract
Background: Inhaled corticosteroids are effective for the treatment of equine asthma but they induce cortisol suppression with potential side effects.

Objectives: To study the efficacy of ciclesonide, an inhaled corticosteroid with an improved safety profile, on lung function, clinical signs related to airway obstruction, and serum cortisol levels in asthmatic horses exposed to a mouldy hay challenge.

Study design: Cross-over placebo controlled, blinded, randomised experiment.

Methods: Sixteen horses were enrolled in three subsequent dose-titration studies (8 horses/study) to investigate the effects of inhaled ciclesonide administered for 2 weeks at doses ranging from 450 to 2700 μg twice daily or 3712.5 μg once daily. Systemic dexamethasone (0.066 mg/kg per os) was our positive control. A placebo group was also studied. Lung function and clinical scores were blindly performed before and after 7 and 14 days of treatment. Serum cortisol was measured before and after 3, 5, 7, 10, 14 days of treatment as well as 3 and 7 days post treatment.

Results: After 7 days, dexamethasone induced a significant reduction in pulmonary resistance (from 2.5 ± 0.6 at day 0 to 1.1 ± 0.7 cm H2 O/L/s), pulmonary elastance (5.0 ± 2.6 to 1.2 ± 1.0 cm H2 O/L), and of the weighted clinical score (14.8 ± 4.7 to 8.0 ± 4.4). Similarly, ciclesonide 1687.5 μg twice daily significantly improved pulmonary resistance (2.7 ± 1.1 to 1.6 ± 0.8 cm H2 O/L/s), pulmonary elastance (5.2 ± 3.1 to 2.2 ± 1.3 cm H2 O/L), and weighted clinical score (13 ± 2.9 to 10.8 ± 4.2). Serum cortisol suppression (<50 nmol/L) systematically occurred with dexamethasone from day 3 of treatment up to day 3 post treatment, but not with ciclesonide at any tested doses. Placebo did not exert any significant beneficial effect.

Main limitations: Experimentally induced asthma exacerbations in horses might respond differently to treatment than naturally occurring exacerbations.
Conclusions: Inhaled ciclesonide is an effective treatment for horses with equine asthma. Serum cortisol was unaffected by treatment.
Keywords: RAO; cortisol; horse; inhalation therapy; inhaled corticosteroids; lung function.
© 2019 Université de Montréal. Equine Veterinary Journal published John Wiley & Sons Ltd on behalf of EVJ Ltd.