Time course of action of fluticasone propionate versus budesonide

Abstract

The slow onset of the beneficial effects of inhaled corticosteroids (ICSs) in asthma contributes to the difficulty of comparing the efficacy of comparable doses of different ICS preparations. This study was predicated on the authors' previous conclusions that an increase in the provocative dose of adenosine monophosphate causing a 20% fall in forced expiratory volume in 1 second (PD20AMP) is a sensitive measure of the anti-inflammatory effects of ICSs in asthma. They then compared the effect of fluticasone propionate (Flut-1500 μg/day) versus budesonide (Bud-1600 μg/day) versus placebo in a 3-way, randomized, crossover study of 18 adults with mild asthma. Each subject received each treatment for 4 weeks with 2-week washout periods between treatments. The PD20AMP and FEV1 were assessed both before and on a weekly basis during each treatment period. The time taken to achieve 50% of the maximum response (T50%) was determined as a measure of the onset of action of each treatment. There was a similar temporal pattern of progressive increases in the PD20AMP during the 4 weeks of treatment with either Flut or Bud. No such increase was seen during the placebo treatment period. The median increases in doubling doses in the PD20AMP after 1 and 4 weeks of treatment were quite similar for Flut and Bud. The median T50% values for Flut and Bud were 9.3 and 7.5 days—not significantly different. There was considerable variation in the PD20AMP responses among the study subjects. However, there was a good correlation between the effects of Flut and Bud on the PD20AMP in individual subjects. The FEV1 and morning peak expiratory flow rate increased variably during the first week of each active treatment and were stable thereafter, while the PD20AMP continued to increase. There was a small progressive improvement in nocturnal asthma symptoms during both active treatments. The authors concluded that the onset of and maximal therapeutic effects in asthma were similar for these doses of Flut and Bud. However, other studies have concluded that the doses used in the current study were in the relatively flat portion of the dose-response curve for most ICS agents in mild-moderate asthma. Therefore, it would be of interest to see a comparison between these two ICS agents used in lower daily doses.(Phillips et al. Thorax 2004;59:26-30.) The slow onset of the beneficial effects of inhaled corticosteroids (ICSs) in asthma contributes to the difficulty of comparing the efficacy of comparable doses of different ICS preparations. This study was predicated on the authors' previous conclusions that an increase in the provocative dose of adenosine monophosphate causing a 20% fall in forced expiratory volume in 1 second (PD20AMP) is a sensitive measure of the anti-inflammatory effects of ICSs in asthma. They then compared the effect of fluticasone propionate (Flut-1500 μg/day) versus budesonide (Bud-1600 μg/day) versus placebo in a 3-way, randomized, crossover study of 18 adults with mild asthma. Each subject received each treatment for 4 weeks with 2-week washout periods between treatments. The PD20AMP and FEV1 were assessed both before and on a weekly basis during each treatment period. The time taken to achieve 50% of the maximum response (T50%) was determined as a measure of the onset of action of each treatment. There was a similar temporal pattern of progressive increases in the PD20AMP during the 4 weeks of treatment with either Flut or Bud. No such increase was seen during the placebo treatment period. The median increases in doubling doses in the PD20AMP after 1 and 4 weeks of treatment were quite similar for Flut and Bud. The median T50% values for Flut and Bud were 9.3 and 7.5 days—not significantly different. There was considerable variation in the PD20AMP responses among the study subjects. However, there was a good correlation between the effects of Flut and Bud on the PD20AMP in individual subjects. The FEV1 and morning peak expiratory flow rate increased variably during the first week of each active treatment and were stable thereafter, while the PD20AMP continued to increase. There was a small progressive improvement in nocturnal asthma symptoms during both active treatments. The authors concluded that the onset of and maximal therapeutic effects in asthma were similar for these doses of Flut and Bud. However, other studies have concluded that the doses used in the current study were in the relatively flat portion of the dose-response curve for most ICS agents in mild-moderate asthma. Therefore, it would be of interest to see a comparison between these two ICS agents used in lower daily doses. (Phillips et al. Thorax 2004;59:26-30.)