Improved Asthma Control After Changing From Low-to-Medium Doses of Other Inhaled Corticosteroids to Low-Dose Fluticasone Propionate

Stuart W. Stoloff, MD, Sharon H. Srebro, MD, Lisa D. Edwards, PhD, Marty C. Johnson, MS, Kathleen A. Rickard, MD

Disclosures
In This Article

Discussion

This retrospective analysis of a large database of asthma patients originally enrolled in 15 clinical trials demonstrated that pulmonary function was either maintained or improved when patients replaced low-to-medium doses of inhaled corticosteroids such as beclomethasone dipropionate, triamcinolone acetonide, or flunisolide with a lower microgram/day dose of fluticasone propionate. Significantly greater improvements from baseline FEV1, morning and evening PEF, asthma symptoms score, and percent symptom-free days were seen in patients who changed from low-dose beclomethasone dipropionate (336 mcg/day) to low-dose fluticasone propionate (176 or 200 mcg/day), compared with those who continued treatment with low-dose beclomethasone dipropionate. The safety profile was comparable, with a similar incidence of drug-related adverse events in the 2 treatment groups. These results are consistent with previously reported results of individual studies comprising this database.[9,11]

Several studies have demonstrated that doses of fluticasone propionate as low as 100 mcg/day improved lung function; reduced symptom severity, rescue albuterol use, and nocturnal awakenings; prevented exacerbations; and improved quality of life in patients with mild-to-moderate asthma compared with placebo.[18,19,20,21,22] In randomized comparative trials, fluticasone propionate at doses of 100 to 500 mcg/day also provided better control of persistent asthma than recommended doses of nonsteroidal agents such as oral theophylline,[23] zafirlukast,[24] or inhaled nedocromil.[25]

The efficacy of low-dose fluticasone propionate compared with recommended doses of other inhaled corticosteroids has been evaluated in several randomized clinical trials in patients with mild-to-moderate asthma. Fluticasone propionate 200 mcg/day showed similar improvements in spirometric assessments of lung function as beclomethasone dipropionate 400 mcg/day.[12,26] In one of the studies included in the current analysis, fluticasone propionate 176 mcg/day significantly increased FEV1 and morning PEF and decreased asthma symptoms and albuterol use compared with 2 higher doses of beclomethasone dipropionate (336 or 672 mcg/day).[11] In other studies, fluticasone propionate 200 mcg/day was also shown to be at least as effective as budesonide 400 mcg/day.[13,27,28]

Comparative studies of fluticasone propionate vs flunisolide or triamcinolone acetonide in patients with moderate to severe asthma have been conducted utilizing higher doses of fluticasone propionate. At doses of 500 mcg/day, fluticasone propionate treatment resulted in significantly greater improvements in lung function when compared with flunisolide 1000 mcg/day.[29] Significantly greater improvements in pulmonary function and asthma control were seen with fluticasone propionate 440 mcg/day (metered dose inhaler) or 500 mcg/day (dry powder inhaler) vs triamcinolone acetonide 800 or 1200 mcg/day.[9,10,30]

Consistent with these results, approximately 40% to 60% of patients who changed from low-to-medium doses of other inhaled corticosteroids to low-dose fluticasone propionate showed further improvements, while approximately 14% to 48% maintained lung function and asthma control. The magnitude of these improvements was independent of the type of prior inhaled corticosteroid used. Additionally, subanalyses of groups of patients with varying degrees of asthma severity revealed that regardless of baseline asthma severity level, treatment with fluticasone propionate 176 or 200 mcg/day resulted in significantly greater improvements in lung function compared with beclomethasone dipropionate 336 mcg/day.

Comparative studies in children with mild-to-moderate asthma have shown that fluticasone propionate was more effective than 80 mg/day cromolyn sodium when administered at 100 mcg/day,[31] was at least as effective as 400 mcg/day beclomethasone dipropionate when dosed at 200 mcg/day,[32] and was more effective than budesonide when both drugs were administered at 400 mcg/day.[33] In the current analysis of data from 4 randomized, double-blind, parallel-group studies, children previously treated with beclomethasone dipropionate, flunisolide, or triamcinolone acetonide showed a significantly greater improvement in all efficacy parameters when subsequently treated with fluticasone propionate doses as low as 100 mcg/day.

Although concerns exist regarding potential systemic effects of inhaled corticosteroid therapy, only minimal systemic effects have been reported at doses <= 400 mcg in children and <= 800 mcg in adults,[34] and there is no evidence of clinical HPA-axis insufficiency at recommended doses.[35] In the present analysis, adults who changed to lower doses of fluticasone propionate had a safety profile that was comparable to that of patients who remained on beclomethasone dipropionate, and pediatric patients previously treated with other inhaled corticosteroids had a low incidence of drug-related adverse events (5%) after treatment with lower doses of fluticasone propionate.

In the original studies comprising this database, fluticasone propionate at 176 or 200 mcg/day showed no significant effects on morning plasma cortisol,[18,20,36,37] or after cosyntropin stimulation[18,37] in adults, or on morning cortisol in children.[38,39] Additionally, growth in children treated with 100 to 200 mcg/day fluticasone propionate was comparable to those treated with placebo.[40] In contrast, a recent comparative study showed detrimental effects on growth and significant HPA-axis effects in prepubertal children treated with beclomethasone dipropionate 400 mcg/day over a period of 20 months. These systemic effects were not seen with fluticasone propionate 100 mcg/day.[41]

This study has several potential limitations. The control group (patients who remained on beclomethasone dipropionate) may not have been optimal. However, the treatment differences seen in the present study are similar to those of another comparative study in which asthma patients were switched from their previous inhaled corticosteroid to either fluticasone propionate or beclomethasone dipropionate.[11] The treatment differences seen in the present study could potentially be attributed to a clinical trial effect (ie, related to greater compliance or increased patient care as a result of enrolling in a clinical trial). However, the fact that similar results have been seen in studies that directly compared fluticasone propionate with beclomethasone dipropionate[11] or triamcinolone acetonide[9,30] in corticosteroid-dependent patients indicates that the differences seen in the present study are likely to be treatment-related.

In conclusion, the results of this analysis demonstrate that patients changing from low-to-medium doses of other inhaled corticosteroids to the lowest recommended dose of fluticasone propionate showed similar or greater control of asthma. These data suggest that fluticasone propionate is more effective than other inhaled corticosteroids at a much lower dose, thus allowing for an increased benefit with an improved safety profile. Therefore, changing to low-dose fluticasone propionate should be considered as a treatment option in patients with asthma.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....