Sustained bronchoprotection, bronchodilatation, and symptom control during regular formoterol use in asthma of moderate or greater severity. The Canadian FO/OD1 Study Group.

BACKGROUND: Recent studies have raised concern that regular inhalation of beta2 -agonists may cause a worsening of asthma control compared with on-demand dosing regimens. OBJECTIVE: The objective of this study was to compare the effect of twice daily formoterol (Foradil), 4 times daily albuterol, and on-demand albuterol on bronchial hyperresponsiveness (BHR), lung function measurements, symptoms, and other indicators of disease control over 6 months inpatients with asthma of moderate or greater severity receiving concomitant inhaled corticosteroids. We also looked for occurrence of rebound BHR on discontinuation of treatment. METHODS: This was a multicenter, parallel-group, double-blind, clinical trial. Methacholine PC20 was the primary outcome variable. Other outcome variables included symptom scores, use of rescue medication, morning peak expiratory flow (PEF), serial FEV1 measurements, and asthma exacerbations. RESULTS: Of the 271 randomized patients, 217 completed the study. Formoterol was significantly superior to on-demand albuterol with regard to methacholine PC20, FEV1, PEF, symptom scores, and use of rescue medication at each measured time point/interval. Regular albuterol was superior to on-demand albuterol with regard to PC20 and FEV1, but not PEF or various clinical scores. After a small drop in the magnitude of bronchoprotection and bronchodilatation occurring shortly after randomization, there was no evidence of progressive tolerance to either regular treatment for any of the measured variables or of rebound increase in BHR 2 days after the end of treatment. The formoterol group had the lowest number of exacerbation days, as defined by high intake of rescue bronchodilator and/or symptom scores, whereas the number of exacerbations requiring increased corticosteroid coverage was similar in the 3 groups. CONCLUSION: In patients with asthma of moderate or greater severity receiving inhaled corticosteroids, formoterol taken twice daily resulted in superior bronchoprotection, bronchodilatation, and clinical control compared with on-demand albuterol over 6 months. Four times daily albuterol was superior to on-demand albuterol for only some of the end points. Progressive tolerance and a rebound increase in BHR on discontinuation of beta-agonists were not found

The extrapulmonary effects of increasing doses of formoterol in patients with asthma.

OBJECTIVE: To assess the cardiovascular and metabolic responses to increasing doses of formoterol administered from a dry powder inhaler. METHODS: Twenty patients with mild to moderate asthma were given 12, 24, 48 and 96 microg of formoterol or a matched placebo on separate days. The doses were administered using a randomised, cross-over, double-blind design. The effects on heart rate, blood pressure, electromechanical systole (QS2I), the electrocardiographic QTc interval, plasma potassium (K); blood glucose and FEV1 were assessed prior to, and for 9 h following each dose. RESULTS: There was no difference between the maximum effects of formoterol 12 microg and placebo; the 24 microg dose significantly decreased plasma K (-0.2 mmol x l(-1)) and increased blood glucose (1.8 mmol x l(-1)) compared to placebo. The two highest doses affected most of the variables with the 96 microg dose being significantly different from placebo for all indices, heart rate (9 beats x min(-1)), systol BP (4 mmHg), diastolic BP (-3 mmHg), QS2I (-11 ms), QTc (17 ms), plasma K (-0.5 mmol x l(-1)) and blood glucose (2.6 mmol x l(-1)). All doses of formoterol increased FEV1. CONCLUSION: Although there were dose-dependent effects on the extrapulmonary measurements, only the effects at the highest dose may be of clinical significance.

Cost-effectiveness analysis of formoterol versus salmeterol in patients with asthma.

OBJECTIVE: The aim of this study was to determine the relative economic consequences of treating asthmatics with twice daily dry powder formoterol 12 micrograms as compared with salmeterol 50 micrograms from a societal perspective. DESIGN AND SETTING: A randomised, 6-month, open-label study including 482 patients with asthma was conducted in Italy, Spain, France, Switzerland, the UK and Sweden. Medical costs included the costs of medications, physician services, emergency room visits, hospital admissions and lung function and other tests. Travel costs and costs of production loss were also calculated. Unit prices were estimated from external sources. To pool the costs of the 6 countries, European currencies were converted to US dollars using 1995 exchange rates. Outcome measures were the number of episode-free days (EFDs) and the number of patients reaching a clinically relevant improvement in quality of life as measured using the St. Georges Respiratory Questionnaire. MAIN OUTCOME MEASURES AND RESULTS: There were no significant differences between the 2 treatment arms in the frequency of emergency room visits, hospital admissions, use of rescue medication or contacts with general practitioners (GPs), specialists or nurses. Median medical costs over 6 months were $US828 per patient with formoterol and $US850 with salmeterol. This difference was not statistically significant. In both groups, about 60% of all days were episode-free. Average costs per EFD were about $US9 for both treatments. The average cost per patient reaching a clinically relevant improvement in quality of life was between $US1300 and $US1400. Incremental cost-effectiveness ratios were not calculated because both costs and outcomes were not significantly different. Asthma-related absenteeism ranged between 3 days and 6 months per patient in both groups. CONCLUSIONS: There was no evidence to suggest that either treatment was more cost effective than the other.