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.


CONCLUSIONS
These results support the emerging role of roflumilast, 500 microg/d, in the treatment of asthma.
Bateman
Eric D
ED
Division of Pulmonology, Department of Medicine, University of Cape Town, South Africa. ebateman@uctgsh1.uct.ac.za
Izquierdo
Jose Luis
JL
Harnest
Ulf
U
Hofbauer
Peter
P
Magyar
Pal
P
Schmid-Wirlitsch
Christine
C
Leichtl
Stefan
S
Bredenbröker
Dirk
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D000631:Aminopyridines / Q000627:therapeutic use*; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D001549:Benzamides / Q000627:therapeutic use*; D002648:Child; D003521:Cyclopropanes / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D012129:Respiratory Function Tests
D000631:Aminopyridines; D018927:Anti-Asthmatic Agents; D001549:Benzamides; D003521:Cyclopropanes; D010726:Phosphodiesterase Inhibitors; C424423:Roflumilast