Roflumilast for asthma: Efficacy findings in placebo-controlled studies.

Background: The role of roflumilast as a potential asthma treatment is not yet fully understood. A series of placebo-controlled trials were undertaken in order to investigate the safety and efficacy of roflumilast in asthma.

Aim: To evaluate the efficacy of roflumilast in nine randomized proof-of-concept, placebo-controlled monotherapy and combination therapy phase II and III clinical studies performed between 1997 and 2005.

Methods: The studies were conducted at sites in Europe, North and South America, Africa, Australasia and Asia and study length varied from 4 to 24 weeks. Data were analyzed from 4873 patients, 12-70 years of age, of whom 2668 received roflumilast. At randomization patients had a forced expiratory flow (FEV1) of 45-90%. Roflumilast was investigated at doses of 125, 250 and 500 μg versus placebo. In two studies, 500 μg roflumilast was added on top of standard therapy with inhaled corticosteroids (ICS), 250 μg fluticasone propionate, or 400 μg beclomethasone dipropionate (BDP). Improvement in FEV1 from baseline was the primary endpoint in seven studies. Key secondary endpoints included asthma symptom scores and time to first severe exacerbation.

Results: Roflumilast consistently improved FEV1 across the nine studies compared with placebo, reaching statistical significance in three studies. When given in addition to ICS, roflumilast provided additional improvements in FEV1 which was statistically significant for 500 μg roflumilast/400 μg BDP versus placebo/400 μg BDP.

Conclusion: Together these studies show that roflumilast has potential as an effective anti-inflammatory therapy for the treatment of asthma. Additional beneficial effects are observed when given in combination with ICS, which warrant further investigation. All studies were funded by Takeda. Trial registration numbers available on ClinicalTrials.gov: NCT00073177, NCT00076076, NCT00163527.