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.