Adjustable maintenance dosing with budesonide/formoterol compared with fixed-dose salmeterol/fluticasone in moderate to severe asthma.
BACKGROUND
Current asthma guidelines recommend that patients are educated to adjust their medication according to their asthma severity using physician-guided self-management plans. However, many patients take a fixed dose of their controller medication and adjust their reliever medication according to asthma symptoms.


OBJECTIVE
This study examined whether asthma control improved if patients adjusted the maintenance dose of budesonide/formoterol (Symbicort Turbuhaler* 160/4.5 microg) according to asthma severity compared with traditional fixed dosing (FD) regimens.


METHODS
Symptomatic patients with asthma (n = 658, mean symptom score 1.5, mean inhaled corticosteroids 735 microg/day, mean forced expiratory volume in 1 second [FEV(1)] 84% predicted) were randomised after 2 weeks' run-in to either: budesonide/formoterol adjustable maintenance dosing (AMD), budesonide/formoterol FD or salmeterol/fluticasone (Seretide Diskus dagger 50/250 microg) FD. In a 4-week double-blind period, both budesonide/formoterol AMD and FD groups received two inhalations twice daily (bid) and salmeterol/fluticasone FD patients received one inhalation bid. In the following 6-month open extension, both FD groups continued with the same treatment. Patients in the AMD group with well-controlled asthma stepped down to one inhalation bid; others continued with two inhalations bid. All AMD patients could increase to four inhalations bid for 7-14 days if symptoms worsened. All patients used terbutaline or salbutamol for symptom relief throughout. The primary variable was the odds of achieving a well-controlled asthma week (WCAW).


RESULTS
The odds ratio for achieving a WCAW did not differ between the FD regimens; however, during the open period, budesonide/formoterol AMD increased the odds of achieving a WCAW vs. budesonide/formoterol FD (odds ratio 1.335; 95% CI: 1.001, 1.783; p = 0.049) despite a 15% reduction in average study drug use. Budesonide/formoterol AMD patients had a lower exacerbation rate over the study: 40% lower vs. salmeterol/fluticasone FD (p = 0.018); 32% lower vs. budesonide/formoterol FD (NS). During the double-blind period, there were no clinically relevant differences between the budesonide/formoterol FD and salmeterol/fluticasone FD groups. Budesonide/formoterol AMD patients used less reliever medication in the open extension: 0.58 vs. 0.92 occasions/day for budesonide/formoterol FD (p = 0.001) and 0.80 occasions/day for salmeterol/fluticasone FD (p = 0.011).


CONCLUSIONS
Adjustable maintenance dosing with budesonide/formoterol provides more effective asthma control by reducing exacerbations and reliever medication usage compared with fixed-dose salmeterol/fluticasone.
Department of Pulmonology, Martini Hospital, Groningen, The Netherlands. r.aalbers@mzh.nl
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D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000420:Albuterol / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000191:economics; D000704:Analysis of Variance; D000730:Androstadienes / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D019819:Budesonide / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D002648:Child; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D016527:Drug Costs; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D005260:Female; D000068298:Fluticasone; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D008875:Middle Aged; D012123:Pulmonary Ventilation / Q000187:drug effects; D000068299:Salmeterol Xinafoate
D000730:Androstadienes; D001993:Bronchodilator Agents; D004338:Drug Combinations; D004983:Ethanolamines; D019819:Budesonide; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol; D000068759:Formoterol Fumarate