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Review of efficacy of ciclesonide for the treatment of asthma in children.

ABSTRACT: Background: Ciclesonide (CIC) is an inhaled corticosteroid (ICS) approved for the maintenance treatment of asthma in patients ages ≥ 12 years. The prodrug aspect of CIC is associated with a safety profile that may make it ideal for children. Objective: The objective was to summarize efficacy results from the eight phase III, randomized, double-blind, controlled trials in children with asthma conducted during CIC clinical development. Methods: Four trials compared CIC 40, 80, or 160 µg/day with placebo. Two trials compared CIC 160 µg/day with fluticasone propionate 200 µg/day, one trial compared CIC 80 or 160 µg/day with fluticasone 200 µg/day, and one trial compared CIC 160 µg/day with budesonide 400 µg/day. Results: The primary end point was met by at least two CIC doses versus placebo in the trials in which the primary end point was the change from baseline in lung function outcome (forced expiratory volume in 1 second [FEV₁] % predicted or morning peak expiratory flow [PEF]). A trial that compared CIC with placebo did not meet the primary end point of superiority in time-to-first severe wheeze exacerbation or lack of improvement. The primary end point of noninferiority to the active control (fluticasone or budesonide) in the change from baseline in a lung function outcome (FEV₁, morning PEF, evening PEF) was met with the CIC 160-µg dose in all active control trials. CIC generally demonstrated statistically significant improvements in forced expiratory flow at 25%-75% of forced vital capacity, asthma symptoms, rescue medication use, and asthma control when compared with placebo and noninferiority for these outcomes compared with fluticasone or budesonide. Conclusion: In children with asthma, once-daily CIC significantly improved large and small airway function, asthma symptoms, and asthma control, and reduced rescue medication use compared with placebo. CIC was comparable with other ICS used to treat asthma in children, which demonstrated its worth for the pediatric population.

SUBMITTER: Blaiss M

PROVIDER: S-EPMC8654387 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Parental concerns about the adverse effects of asthma medications can lead to nonadherence and uncontrolled asthma in children. Ciclesonide (CIC) is a prodrug, with low oropharyngeal deposition and bioavailability that may minimize the risk of local and systemic adverse effects. CIC is U.S. Food and Drug Administration approved for asthma in children ages ≥ 12 years. Objective: To summarize safety results from the 13 phase II or III randomized controlled trials conducted in children with asthma during CIC clinical development. Methods: Four 12- to 24-week trials compared the safety of once-daily CIC 40, 80, or 160 µg/day with placebo; four 12-week trials compared the safety of CIC 80 or 160 µg/day with either fluticasone or budesonide; one 12-month trial compared the long-term safety of CIC 40, 80, or 160 µg/day with fluticasone; one 12-month trial compared growth velocity of CIC 40 or 160 µg/day with placebo; and three cross-over trials compared short-term growth velocity and hypothalamic-pituitary-adrenal (HPA) axis effects of CIC 40, 80, or 160 µg/day with placebo or fluticasone. Results: In all, 4399 children were treated with CIC. The incidence of treatment-emergent adverse events (AE) was similar among the CIC doses and between CIC and placebo in short-term studies and between CIC and fluticasone in the long-term safety study. No CIC-related serious AEs were reported in any study. The incidence of treatment-related oral candidiasis was low and similar between CIC (≤0.5%) and placebo (≤0.7%) or active controls (≤0.5%) in the short-term studies. There was no clinically relevant HPA axis suppression or reduction in growth velocity associated with CIC. Conclusion: Data from 13 studies demonstrate that CIC is associated with low rates of oropharyngeal AEs, with no indication of clinically relevant systemic effects in children with asthma. The favorable safety profile and demonstrated improvements in asthma control make CIC an ideal inhaled corticosteroid for the treatment of asthma in children.

Project description:ImportanceSystemic corticosteroids are commonly used in treating severe COVID-19. However, the role of inhaled corticosteroids in the treatment of patients with mild to moderate disease is less clear.ObjectiveTo determine the efficacy of the inhaled steroid ciclesonide in reducing the time to alleviation of all COVID-19-related symptoms among nonhospitalized participants with symptomatic COVID-19 infection.Design, setting, and participantsThis phase 3, multicenter, double-blind, randomized clinical trial was conducted at 10 centers throughout the US and assessed the safety and efficacy of a ciclesonide metered-dose inhaler (MDI) for treating nonhospitalized participants with symptomatic COVID-19 infection who were screened from June 11, 2020, to November 3, 2020.InterventionsParticipants were randomly assigned to receive ciclesonide MDI, 160 μg per actuation, for a total of 2 actuations twice a day (total daily dose, 640 μg) or placebo for 30 days.Main outcomes and measuresThe primary end point was time to alleviation of all COVID-19-related symptoms (cough, dyspnea, chills, feeling feverish, repeated shaking with chills, muscle pain, headache, sore throat, and new loss of taste or smell) by day 30. Secondary end points included subsequent emergency department visits or hospital admissions for reasons attributable to COVID-19.ResultsA total of 413 participants were screened and 400 (96.9%) were enrolled and randomized (197 [49.3%] in the ciclesonide arm and 203 [50.7%] in the placebo arm; mean [SD] age, 43.3 [16.9] years; 221 [55.3%] female; 2 [0.5%] Asian, 47 [11.8%] Black or African American, 3 [0.8%] Native Hawaiian or other Pacific Islander, 345 [86.3%] White, and 1 multiracial individuals [0.3%]; 172 Hispanic or Latino individuals [43.0%]). The median time to alleviation of all COVID-19-related symptoms was 19.0 days (95% CI, 14.0-21.0) in the ciclesonide arm and 19.0 days (95% CI, 16.0-23.0) in the placebo arm. There was no difference in resolution of all symptoms by day 30 (odds ratio, 1.28; 95% CI, 0.84-1.97). Participants who were treated with ciclesonide had fewer subsequent emergency department visits or hospital admissions for reasons related to COVID-19 (odds ratio, 0.18; 95% CI, 0.04-0.85). No participants died during the study.Conclusions and relevanceThe results of this randomized clinical trial demonstrated that ciclesonide did not achieve the primary efficacy end point of reduced time to alleviation of all COVID-19-related symptoms.Trial registrationClinicalTrials.gov Identifier: NCT04377711.

Project description:BackgroundGastroesophageal reflux is common among patients with asthma but often causes mild or no symptoms. It is not known whether treatment of gastroesophageal reflux with proton-pump inhibitors in patients who have poorly controlled asthma without symptoms of gastroesophageal reflux can substantially improve asthma control.MethodsIn a parallel-group, double-blind trial, we randomly assigned 412 participants with inadequately controlled asthma, despite treatment with inhaled corticosteroids, and with minimal or no symptoms of gastroesophageal reflux to receive either 40 mg of esomeprazole twice a day or matching placebo. Participants were followed for 24 weeks with the use of daily asthma diaries, spirometry performed once every 4 weeks, and questionnaires that asked about asthma symptoms. We used ambulatory pH monitoring to ascertain the presence or absence of gastroesophageal reflux in the participants. The primary outcome was the rate of episodes of poor asthma control, as assessed on the basis of entries in asthma diaries.ResultsEpisodes of poor asthma control occurred with similar frequency in the placebo and esomeprazole groups (2.3 and 2.5 events per person-year, respectively; P=0.66). There was no treatment effect with respect to individual components of the episodes of poor asthma control or with respect to secondary outcomes, including pulmonary function, airway reactivity, asthma control, symptom scores, nocturnal awakening, or quality of life. The presence of gastroesophageal reflux, which was documented by pH monitoring in 40% of participants with minimal or no symptoms, did not identify a subgroup of patients that benefited from treatment with proton-pump inhibitors. There were fewer serious adverse events among patients receiving esomeprazole than among those receiving placebo (11 vs. 17).ConclusionsDespite a high prevalence of asymptomatic gastroesophageal reflux among patients with poorly controlled asthma, treatment with proton-pump inhibitors does not improve asthma control. Asymptomatic gastroesophageal reflux is not a likely cause of poorly controlled asthma. (ClinicalTrials.gov number, NCT00069823.)

Project description:BackgroundThe inhaled corticoteroid (ICS) ciclesonide (Cic), controls asthma symptoms in the majority of patients at the recommended dose of 160 µg/day. However, the relationship between the level of asthma control and increasing doses of Cic is unknown. This study investigated whether long-term treatment with higher doses of Cic would further improve asthma symptoms in patients with uncontrolled asthma despite ICS use.Patients and methodsIn a double-blind, randomized, parallel-group study, 367 patients were allocated to one of three treatment arms (Cic 160, 320 and 640 µg/day). After a single-blind, 3-week baseline period with Cic 160 µg/day, eligible patients were randomized to receive 52 weeks of treatment with Cic 160, 320 or 640 µg/day (double-blind period) during which forced expiratory volume in 1 second (FEV1), exacerbations and Asthma Control Questionnaire (ACQ) scores were measured.ResultsTreatment with all the three doses was associated with significant improvements in ACQ scores, FEV1 and asthma symptoms (P<0.01). There were no statistically significant differences between the three doses. The results of the primary end point analysis showed a numerical improvement in the ACQ score with Cic 640 µg/day compared with Cic 160 µg/day (least square [LS] mean: -0.122; two-sided P-value: 0.30). Post hoc subgroup analyses showed that the improvement in the ACQ score with Cic 640 µg/day compared with Cic 160 µg/day was statistically significant in subjects who experience at least one exacerbation per year (LS mean: -0.586; 95% confidence interval: -1.110, -0.062, P=0.0285). Adverse events were low and consistent with the known safety profile of Cic.ConclusionIn patients with persistent, uncontrolled asthma, increasing the Cic dose from 160 to 640 µg/day provided no clear additional effect. Patients who experience more than one exacerbation per year may benefit from higher doses; however, further studies are necessary to confirm this. All Cic doses were well tolerated.

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Review of efficacy of ciclesonide for the treatment of asthma in children.

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