Salmeterol/fluticasone propionate (50/500 microg) in combination in a Diskus inhaler (Seretide) is effective and safe in the treatment of steroid-dependent asthma.
This multicentre double-blind, double-dummy study compared the safety and efficacy of a new combination Diskus inhaler containing both salmeterol 50 microg and fluticasone propionate 500 microg (Seretide, GlaxoWellcome, France) with the same doses of the two drugs delivered via separate Diskus inhalers and with the same dose of fluticasone propionate alone. Patients were eligible for study entry if they had received an inhaled corticosteroid continuously for 12 weeks prior to run-in, and had received treatment with beclomethasone dipropionate or budesonide 1500-2000 microg day(-1) or fluticasone propionate 750-1000 microg day(-1) for at least 4 weeks prior to run-in. In total, 503 patients receiving inhaled corticosteroids were randomized to 28 weeks' treatment with either salmeterol/fluticasone propionate (50/500 microg) via a single Diskus inhaler (combination) and placebo, or salmeterol 50 microg and fluticasone propionate 500 microg administered via separate Diskus inhalers (concurrent), or fluticasone propionate 500 microg and placebo. All treatments were administered twice daily, mean morning peak expiratory flow rate (PEFR) and asthma symptoms were measured for the first 12 weeks and safety data were collected throughout the 28-week study. Over weeks 1 to 12, improvement in adjusted mean morning PEFR was 35 and 33 l min(-1), respectively, in the combination and concurrent therapy treatment groups (12 and 10% increase from baseline, respectively). The mean difference between treatments was -3 l min(-1) (90% confidence interval -10.4 l min(-1)) which was within the criteria for clinical equivalence. However, the combination therapy was statistically significantly superior to fluticasone propionate alone for mean morning PEFR (P<0.001) and other measures of lung function, whilst clinical equivalence of the combination and concurrent therapies was observed. All three treatments were well tolerated. In addition, there were no differences between the three treatments in either the c.hange in serum cortisol or urinary cortisol concentrations, which, for each treatment group, were no significantly different from baseline at the end of the treatment period. Thus, the combination of salmeterol and fluticasone propionate in a single inhaler is as well tolerated and effective in achieving asthma control in steroid-dependent patients as the separate administration of the two drugs, and both combination and concurrent therapy are superior to administration of the same dose of corticosteroid alone.
Aubier
M
M
Unit de Pneumologie-8é Sud, Hospital Bichat, Paris, France.
Pieters
W R
WR
Schlösser
N J
NJ
Steinmetz
K O
KO
D000280:Administration, Inhalation; D000287:Administration, Topical; D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000368:Aged; D000420:Albuterol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000730:Androstadienes / Q000008:administration & dosage* / Q000009:adverse effects; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D004311:Double-Blind Method; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume; D005938:Glucocorticoids; D006801:Humans; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D010366:Peak Expiratory Flow Rate; D000068299:Salmeterol Xinafoate
D000318:Adrenergic beta-Agonists; D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D004338:Drug Combinations; D005938:Glucocorticoids; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol