Ciclesonide Reduces the Need for Oral Steroid Use in Adult Patients With Severe, Persistent Asthma: Discussion
HPA-Axis Evaluation: Unstimulated (basal) mean serum cortisol levels increased significantly from baseline to end point in the CIC640 group (3.58 ^g/dL [SE 0.97]; 95% CI, 1.66 to 5.51) and the CIC1280 group (2.34 ^g/dL [SE 1.01]; 95% CI, 0.33 to 4.35). Cortisol levels within the placebo group also rose but not significantly (1.33 ^g/dL [SE 1.01]; 95% CI, – 0.67 to 3.34). Between-treatment differences in the baseline to end point change in basal serum cortisol levels were not statistically significant (CIC640, p = 0.1052; CIC1280, p = 0.4829; Table 6). After stimulation with low-dose cosyntropin (1 ^g), a significant increase from baseline to end point in low-dose peak serum cortisol levels was seen in the CIC640 group (5.28 ^g/dL [SE 1.3]; 95% CI, 2.63 to 7.93) and the CIC1280 group (3.55 ^g/dL [SE 1.3]; 95% CI, 0.95 to 6.14). In contrast, no significant change was observed in the placebo group (- 0.16 ^g/dL [SE 1.4]; 95% CI, – 2.92 to 2.61). This difference vs placebo was statistically significant for the CIC640 treatment group (p = 0.0049) but not for the CIC1280 group (p = 0.0537; Table 6). At baseline, 66.0% of patients in the CIC640 group, 60.4% of patients in the CIC1280 group, and 62.2% of patients in the placebo group had suppressed HPA-axis function (according to criteria outlined in the “Materials and Methods” section). At end point, a lower proportion of patients in both ciclesonide treatment groups had suppressed HPA-axis function compared with placebo (CIC640, 46.8%; CIC1280, 43.8%; placebo, 53.3%).
Other Laboratory and Clinical Tests: Laboratory tests, physical examinations, and vital signs showed no clinically meaningful changes in patients from any of the treatment groups.
This study was designed to assess the OCS-sparing potential of ciclesonide in adult and adolescent patients with OCS-dependent, severe, persistent asthma. The results suggested that the substitution of twice-daily inhaled ciclesonide for high doses of other forms of ICS significantly reduced the dose of prednisone required by these patients. Although no significant dose-response effect was noted between the 640 ^g/d and 1,280 ^g/d dosages, the higher dose demonstrated a greater numeric trend toward improvement. In contrast, prednisone use was increased in the placebo group. Additionally, asthma control in the ciclesonide population was maintained or improved, as judged by the trends for improvements in FEV1 and morning PEF; these measures worsened in the placebo group. The OCS-sparing effect of ciclesonide was apparent by week 2 of the treatment and continued throughout the study, enabling almost one third of ciclesonide-treated patients to discontinue OCS use, vs approximately 11% of placebo-treated patients. Source
Table 6—Change From Baseline to End of Study in Unstimulated (Basal) Serum Cortisol Levels and in Low-Dose Peak Serum Cortisol Levels in the ITT Population of Patients With Severe Asthma Receiving Treatment With Ciclesonide, 320 /Jig bid; Ciclesonide, 640 /Jig bid; or Placebo
|Basal serum cortisol, |xg/dL||n = 32||n = 36||n = 32|
|Mean (SE) change from baseline||1.33(1.006)||3.58 (0.967)||2.34 (1.011)|
|95% CI||– 0.67-3.34||1.66-5.51||0.33-4.35|
|Mean (SE) treatment difference vs placebo||2.25 (1.372)||1.01 (1.430)|
|p value vs placebo||0.1052||0.4829|
|Low-dose peak serum cortisol, |xg/dL||n = 35||n = 37||n = 40|
|Mean (SE) change from baseline||– 0.16 (1.390)||5.28(1.332)||3.55 (1.304)|
|95% CI||– 2.92-2.61||2.63-7.93||0.95-6.14|
|Mean (SE) treatment difference vs placebo||5.43(1.876)||3.70(1.891)|
|p value vs placebo||0.0049||0.0537|