Comparison of mometasone furoate dry powder inhaler and fluticasone propionate dry powder inhaler in patients with moderate to severe persistent asthma requiring high-dose inhaled corticosteroid therapy: findings from a noninferiority trial.

BACKGROUND: Inhaled corticosteroids (ICSs) are one of the suggested first-line therapies for patients with persistent asthma of moderate severity. METHODS: The efficacy and safety of mometasone furoate (MF) 400 microg twice daily (BID) and fluticasone propionate (FP) 500 microg BID administered for 12 weeks via dry powder inhaler (DPI) were compared in a noninferiority trial, in adults with moderate-to-severe persistent asthma. The primary variable was the change from baseline in am peak expiratory flow rate (PEFR). PM PEFR, forced expiratory volume in 1 second (FEV(1)), asthma symptoms, rescue medication use, response to therapy, exacerbation rates, and adverse events were also assessed. RESULTS: The lower bound of 95% CIs for treatment differences in the primary variable ranged from 2.6% to 5.6% throughout the 12-week study and were within the prespecified noninferiority range. No significant between-group differences were observed in lung function, rescue medication use, response to therapy, exacerbation rates, or adverse events. At most of the weeks assessed, there were no between-group differences in asthma symptoms. Most adverse events were mild-to-moderate. CONCLUSION: MF-DPI 400 microg BID was therapeutically equivalent to FP-DPI 500 microg BID in patients with moderate-to-severe persistent asthma.

Efficacy and safety of roflumilast in the treatment of asthma.

BACKGROUND: The central role of chronic inflammation of the airways in asthma pathogenesis is supported by the efficacy of corticosteroids in controlling clinical symptoms. However, the search continues for potentially safer anti-inflammatory alternatives. Roflumilast is an oral, once-daily phosphodiesterase type 4 inhibitor with anti-inflammatory activity in preclinical models of asthma and chronic obstructive pulmonary disease. OBJECTIVE: To investigate the dose-ranging efficacy and safety of roflumilast in patients with mild-to-moderate asthma. METHODS: Patients (N = 693) were randomized in a double-blind, parallel-group, phase 2/3 study. After a 1- to 3-week placebo run-in period, patients (mean forced expiratory volume in 1 second [FEV1], 73% of predicted) were randomized to receive 100, 250, or 500 microg of roflumilast once daily for 12 weeks. The primary end point was change from baseline in FEV1; secondary end points included change from baseline in morning and evening peak expiratory flow. RESULTS: Roflumilast use significantly increased FEV1 (P < .001 vs baseline). Improvements from baseline in FEV1 at the last visit were 260, 320, and 400 mL for the 100-, 250-, and 500-microg dose groups, respectively. Roflumilast, 500 microg, was superior to roflumilast, 100 microg, by 140 mL in improving FEV1 (P = .002). There were also significant improvements from baseline in morning and evening peak expiratory flow in all the dose groups (P < or = .006). Roflumilast was well tolerated at all doses tested. Most adverse events were mild to moderate in intensity and transient. CONCLUSION: These results support the emerging role of roflumilast, 500 microg/d, in the treatment of asthma.

Onset and duration of action of formoterol and tiotropium in patients with moderate to severe COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) management guidelines recommend regular treatment with one or more long-acting bronchodilators for patients with moderate to severe COPD. OBJECTIVE: To compare the onset and duration of action of formoterol and tiotropium in patients with COPD. METHODS: This randomized, multicentre, open-label crossover study in 38 patients with COPD (mean age 64 years; mean FEV(1) 55% predicted) assessed the effect of 7 days of treatment with formoterol (12 microg b.i.d. via Foradil Aerolizer) vs. tiotropium (18 microg o.d. via Spiriva HandiHaler) on lung function measured over a period of 12 h after the first dose on day 1 and the last dose on day 8. RESULTS: The primary efficacy variable, FEV(1)-AUC during the first 2 h post-dose (FEV(1)-AUC(10-120 min)), was significantly higher for formoterol compared with tiotropium, with between-treatment differences of 124 ml (p = 0.016) after the first dose and 80 ml (p = 0.036) after 7 days' treatment in favour of formoterol. FEV(1) measured 12 h after inhalation did not differ statistically significantly between treatments. Adverse events occurred in 2 (5%) patients after treatment with formoterol and in 5 (12%) patients after treatment with tiotropium. CONCLUSION: This study demonstrates faster onset of action and greater bronchodilation of formoterol vs. tiotropium for bronchodilation within the first 2 h of inhalation (FEV(1)-AUC(10-120 min)) and comparable bronchodilation 12 h post-inhalation in patients with moderate to severe COPD.