Intranasal Ciclesonide for Allergic Rhinitis in Children
Intranasal Ciclesonide for Allergic Rhinitis in Children
The efficacy and safety of aqueous ciclesonide intranasal spray has been demonstrated in a number of randomized controlled trials involving adults and adolescents. In premarketing studies, aqueous ciclesonide spray produced significant reductions in total nasal symptom scores (TNSS), a composite endpoint encompassing scores for sneezing, nasal discharge, itching, and congestion. These scores are often defined as reflective, representing the patient's assessment of symptoms over the previous 12 hours, or instantaneous, representing symptoms present at the time of documentation.
In a premarketing seasonal allergic rhinitis trial conducted in 324 adults and adolescents, patients received either 200 mcg ciclesonide or placebo once daily for 4 weeks. The change in reflective TNSS from baseline to the end of the trial was significantly greater in the patients receiving ciclesonide (−2.40 in the treatment group and −1.50 in the controls, p < 0.001). The change in instantaneous TNSS was also significant (−1.87 in the treatment group versus −1.03 in the controls, p < 0.001). In a 6-week perennial allergic rhinitis trial, the same dosing scheme produced similar results. The change in reflective TNSS was −2.51 in the treated patients compared to −1.89 in the controls (p < 0.001). The change in instantaneous TNSS was −1.99 in the treatment group compared to −1.46 for the controls (p = 0.004).
Two randomized, blinded, placebo-controlled studies of the aqueous spray were conducted by the manufacturer in children 6 to 11 years of age. Both demonstrated efficacy similar to that achieved in adolescents and adults. A total of 1,282 children were enrolled into either the 2-week dose-ranging study of children with seasonal allergic rhinitis or a 12-week study of children with perennial allergic rhinitis. In the 2-week dose-ranging study, ciclesonide 200 mcg once daily produced a significantly greater improvement in reflective TNSS compared to placebo (−2.46 versus −2.07, p = 0.04), but the 100 mcg dose did not (−2.38 versus −2.07, p = 0.103). In the 12-week trial, the changes in TNSS with ciclesonide were not significantly different than that with placebo, although there was a trend towards improvement with the 200 mcg dose.
To date, ciclesonide HFA intranasal aerosol has only been tested in adolescents and adults. In 2010, Ratner and colleagues conducted a manufacturer-sponsored randomized placebo-controlled trial of ciclesonide HFA for the treatment of seasonal allergic rhinitis. A total of 707 patients were randomized to treatment with either a 80 mcg or 160 mcg ciclesonide dose, or placebo, once daily for 2 weeks. The percentage reduction in reflective TNSS from baseline was 15.1% and 16% in the 80 mcg and 160 mcg groups, significantly greater than the 3.7% reduction in the controls (p < 0.01). Reductions in instantaneous TNSS were 14.3% and 15.4% for the two treatment groups and 6.8% in the controls (p < 0.001). Ocular symptoms were also reduced (15.7% and 15%, compared to 6.8% in the controls, p < 0.001). There were no differences in the frequency of adverse effects.
An additional ciclesonide HFA study by these investigators was published earlier this year, using the product that is now on the market. Adults and adolescents with allergic rhinitis were randomized to receive a ciclesonide HFA dose of either 74 or 148 mcg or placebo once daily for 2 weeks. As in the previous study, patients were assessed by comparing baseline and treatment instantaneous and reflective TNSS and ocular symptom scores. Both treatment groups produced significant improvement in reflective TNSS (a mean change of −1.04 and −1.02 for the 74 and 148 mcg groups respectively, p < 0.001 compared to placebo) and instantaneous TNSS (mean change −0.90 and −0.83, p < 0.001 compared to placebo). Only the lower dose group showed a statistically significant improvement in ocular symptoms (p = 0.0124). The incidence of adverse effects was similar among the groups.
The manufacturer has also conducted a 26-week trial of ciclesonide HFA in adults and adolescents with allergic rhinitis using the same methodology as in the previous study. A total of 472 subjects with seasonal allergic rhinitis were enrolled. As in the previous studies, there was a significantly greater mean change from baseline reflective TNSS in the treated patients than in those given placebo (−1.5 versus −0.5, p < 0.001), as well as the instantaneous TNSS (−1.3 versus −0.5, p < 0.001). The decrease in ocular symptom scores was also significant (−0.8 versus −0.2, p = 0.001). Similar results were seen in the 471 subjects with perennial allergic rhinitis. Mean change for the treatment group was significantly greater in reflective TNSS (−2 compared to −1.3, p < 0.001) and instantaneous TNSS (−1.8 compared to −1.2, p < 0.001).
Clinical Studies
The efficacy and safety of aqueous ciclesonide intranasal spray has been demonstrated in a number of randomized controlled trials involving adults and adolescents. In premarketing studies, aqueous ciclesonide spray produced significant reductions in total nasal symptom scores (TNSS), a composite endpoint encompassing scores for sneezing, nasal discharge, itching, and congestion. These scores are often defined as reflective, representing the patient's assessment of symptoms over the previous 12 hours, or instantaneous, representing symptoms present at the time of documentation.
In a premarketing seasonal allergic rhinitis trial conducted in 324 adults and adolescents, patients received either 200 mcg ciclesonide or placebo once daily for 4 weeks. The change in reflective TNSS from baseline to the end of the trial was significantly greater in the patients receiving ciclesonide (−2.40 in the treatment group and −1.50 in the controls, p < 0.001). The change in instantaneous TNSS was also significant (−1.87 in the treatment group versus −1.03 in the controls, p < 0.001). In a 6-week perennial allergic rhinitis trial, the same dosing scheme produced similar results. The change in reflective TNSS was −2.51 in the treated patients compared to −1.89 in the controls (p < 0.001). The change in instantaneous TNSS was −1.99 in the treatment group compared to −1.46 for the controls (p = 0.004).
Two randomized, blinded, placebo-controlled studies of the aqueous spray were conducted by the manufacturer in children 6 to 11 years of age. Both demonstrated efficacy similar to that achieved in adolescents and adults. A total of 1,282 children were enrolled into either the 2-week dose-ranging study of children with seasonal allergic rhinitis or a 12-week study of children with perennial allergic rhinitis. In the 2-week dose-ranging study, ciclesonide 200 mcg once daily produced a significantly greater improvement in reflective TNSS compared to placebo (−2.46 versus −2.07, p = 0.04), but the 100 mcg dose did not (−2.38 versus −2.07, p = 0.103). In the 12-week trial, the changes in TNSS with ciclesonide were not significantly different than that with placebo, although there was a trend towards improvement with the 200 mcg dose.
To date, ciclesonide HFA intranasal aerosol has only been tested in adolescents and adults. In 2010, Ratner and colleagues conducted a manufacturer-sponsored randomized placebo-controlled trial of ciclesonide HFA for the treatment of seasonal allergic rhinitis. A total of 707 patients were randomized to treatment with either a 80 mcg or 160 mcg ciclesonide dose, or placebo, once daily for 2 weeks. The percentage reduction in reflective TNSS from baseline was 15.1% and 16% in the 80 mcg and 160 mcg groups, significantly greater than the 3.7% reduction in the controls (p < 0.01). Reductions in instantaneous TNSS were 14.3% and 15.4% for the two treatment groups and 6.8% in the controls (p < 0.001). Ocular symptoms were also reduced (15.7% and 15%, compared to 6.8% in the controls, p < 0.001). There were no differences in the frequency of adverse effects.
An additional ciclesonide HFA study by these investigators was published earlier this year, using the product that is now on the market. Adults and adolescents with allergic rhinitis were randomized to receive a ciclesonide HFA dose of either 74 or 148 mcg or placebo once daily for 2 weeks. As in the previous study, patients were assessed by comparing baseline and treatment instantaneous and reflective TNSS and ocular symptom scores. Both treatment groups produced significant improvement in reflective TNSS (a mean change of −1.04 and −1.02 for the 74 and 148 mcg groups respectively, p < 0.001 compared to placebo) and instantaneous TNSS (mean change −0.90 and −0.83, p < 0.001 compared to placebo). Only the lower dose group showed a statistically significant improvement in ocular symptoms (p = 0.0124). The incidence of adverse effects was similar among the groups.
The manufacturer has also conducted a 26-week trial of ciclesonide HFA in adults and adolescents with allergic rhinitis using the same methodology as in the previous study. A total of 472 subjects with seasonal allergic rhinitis were enrolled. As in the previous studies, there was a significantly greater mean change from baseline reflective TNSS in the treated patients than in those given placebo (−1.5 versus −0.5, p < 0.001), as well as the instantaneous TNSS (−1.3 versus −0.5, p < 0.001). The decrease in ocular symptom scores was also significant (−0.8 versus −0.2, p = 0.001). Similar results were seen in the 471 subjects with perennial allergic rhinitis. Mean change for the treatment group was significantly greater in reflective TNSS (−2 compared to −1.3, p < 0.001) and instantaneous TNSS (−1.8 compared to −1.2, p < 0.001).
