Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease

Abstract

The efficacy and safety of budesonide/formoterol in a single inhaler compared with placebo, budesonide and formoterol were evaluated in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).In a 12-month, randomised, double-blind, placebo-controlled, parallel-group study in 812 adults (mean age 64 yrs, mean forced expiratory volume in one second (FEV1) 36% predicted normal), patients received two inhalations twice daily of either budesonide/ formoterol (Symbicort1) 160/4.5 mg (delivered dose), budesonide 200 mg (metered dose), formoterol 4.5 mg or placebo. Severe exacerbations and FEV1 (primary variables), peak expiratory flow (PEF), COPD symptoms, health-related quality of life (HRQL), mild exacerbations, use of reliever b 2 -agonist and safety variables were recorded.Budesonide/formoterol reduced the mean number of severe exacerbations per patient per year by 24% versus placebo and 23% versus formoterol. FEV1 increased by 15% versus placebo and 9% versus budesonide. Morning PEF improved significantly on day 1 versus placebo and budesonide; after 1 week, morning PEF was improved versus placebo, budesonide and formoterol. Improvements in morning and evening PEF versus comparators were maintained over 12 months. Budesonide/formoterol decreased all symptom scores and use of reliever b 2 -agonists significantly versus placebo and budesonide, and improved HRQL versus placebo. All treatments were well tolerated.These results suggest a role for budesonide/formoterol in the long-term management of moderate-to-severe chronic obstructive pulmonary disease. Chronic obstructive pulmonary disease (COPD) is currently the fourth leading cause of death in the world [1], with increasing prevalence and mortality predicted in the coming decades [2]. COPD is a serious and disabling disease, which imposes a large burden on patients, healthcare systems and society.In patients with COPD, lung function deteriorates progressively over several years with increasing symptoms (e.g. dyspnoea, chest tightness, cough and sputum production); acute exacerbations are common, particularly in later stages, and these have considerable impact on patients9 daily activities and well-being [3]. Cigarette smoking is the major aetiological factor in COPD and smoking cessation is the only factor which has been shown to influence the decline in forced expiratory volume in one second (FEV1) [4,5]. However, the COPD-related inflammatory process in the airways initiated by smoking persists after cessation of smoking [6], and effective treatment is needed in past smokers with COPD [7].The pharmacotherapy of COPD largely consists of mucolytics, bronchodilators, such as b 2 -agonists, anticholinergics, theophylline and anti-inflammatory drugs i.e. inhaled corticosteroids, often taken in combination [2]. Consequently, there is a need for better treatment options to relieve symptoms, reduce exacerbations and to provide better health-related quality of life (HRQL) for individual patients. The long-acting b 2 -agonists formoterol a...

A pilot study to assess the effects of combining fluticasone propionate/salmeterol and tiotropium on the airflow obstruction of patients with severe-to-very severe COPD

“…In effect, some papers have documented the advantage for COPD patients in combining long-acting anticholinergic and long-acting ß2-adrenergic agents [3][4][5][6]. Other papers [4][5][6][7][8][9][10][11][12][13][14][15] have clearly shown that both longacting ß2-agonists and inhaled corticosteroids have an important role in COPD, which increases when the two drugs are combined in the same therapeutic regimen.…”

Effective management of COPD in primary care — the role of long-acting beta agonist/inhaled corticosteroid combination therapy

“…Some studies showed clinical benefits with ICS use in moderate to severe but not in mild COPD [33][34][35][36]. ICS use is associated with reductions in the number and severity of exacerbations experienced by patients with severe COPD [34,[36][37][38][39]. In addition, in a pooled analysis of seven randomised studies involving 5085 patients, inhaled corticosteroids reduced all-cause mortality by ∼25% relative to placebo in patients with stable COPD [40].…”

“…These recommendations have been based on a number of long-term (≥6 months) randomised, double-blind, placebocontrolled, parallel group trials assessing the efficacy and safety of combining a LABA with an ICS in a single inhaler [29,[37][38][39][41][42][43]. Outcome measures in these trials included lung function, symptom scores, exacerbation rates, quality of life, and safety and tolerability.…”

“…LABA/ICS combination treatment is associated with improvements in lung function, compared with monotherapy, in severe COPD [29,[37][38][39]41]. Studies show pre-dose FEV 1 is improved by 13-17% over baseline by LABA/ICS treatment and can significantly increase pre-dose and post-dose FEV 1 compared with ICS monotherapy (Table 1) [29,[37][38][39]41].…”

“…Studies show pre-dose FEV 1 is improved by 13-17% over baseline by LABA/ICS treatment and can significantly increase pre-dose and post-dose FEV 1 compared with ICS monotherapy (Table 1) [29,[37][38][39]41]. In patients taking LABA/ICS combination therapy, the withdrawal of ICS therapy is associated with a significant, acute, and persistent deterioration in lung function [44].…”